Relugolix + Estradiol + Norethindrone interactions

Food & lifestyle

• grapefruit juice

  Moderate

  Metabolism

  Grapefruit juice may increase the plasma concentrations of orally administered drugs that are substrates of the CYP450 3A4 isoenzyme. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

  What to do: Patients who regularly consume grapefruit or grapefruit juice should be monitored for adverse effects and altered plasma concentrations of drugs that undergo significant presystemic metabolism by CYP450 3A4. Grapefruit and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact with these drugs.

  32 sources

  1. Edgar B, Bailey D, Bergstrand R, et al. "Acute effects of drinking grapefruit juice on the pharmacokinetics and dynamics on felodipine and its potential clinical relevance." Eur J Clin Pharmacol 42 (1992): 313-7
  2. Jonkman JH, Sollie FA, Sauter R, Steinijans VW "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther 49 (1991): 248-55
  3. Bailey DG, Arnold JM, Munoz C, Spence JD "Grapefruit juice--felodipine interaction: mechanism, predictability, and effect of naringin." Clin Pharmacol Ther 53 (1993): 637-42
  4. Bailey DG, Arnold JMO, Spence JD "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet 26 (1994): 91-8
  5. Sigusch H, Hippius M, Henschel L, Kaufmann K, Hoffmann A "Influence of grapefruit juice on the pharmacokinetics of a slow release nifedipine formulation." Pharmazie 49 (1994): 522-4
  6. Bailey DG, Arnold JM, Strong HA, Munoz C, Spence JD "Effect of grapefruit juice and naringin on nisoldipine pharmacokinetics." Clin Pharmacol Ther 54 (1993): 589-94
  7. Yamreudeewong W, Henann NE, Fazio A, Lower DL, Cassidy TG "Drug-food interactions in clinical practice." J Fam Pract 40 (1995): 376-84
  8. "Grapefruit juice interactions with drugs." Med Lett Drugs Ther 37 (1995): 73-4

  Show all 32 sourcesShow fewer sources

  9. Hukkinen SK, Varhe A, Olkkola KT, Neuvonen PJ "Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice." Clin Pharmacol Ther 58 (1995): 127-31
  10. Min DI, Ku YM, Geraets DR, Lee HC "Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers." J Clin Pharmacol 36 (1996): 469-76
  11. Majeed A, Kareem A "Effect of grapefruit juice on cyclosporine pharmacokinetics." Pediatr Nephrol 10 (1996): 395
  12. Clifford CP, Adams DA, Murray S, Taylor GW, Wilkins MR, Boobis AR, Davies DS "Pharmacokinetic and cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice." Br J Clin Pharmacol 42 (1996): p662
  13. Josefsson M, Zackrisson AL, Ahlner J "Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers." Eur J Clin Pharmacol 51 (1996): 189-93
  14. Kantola T, Kivisto KT, Neuvonen PJ "Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid." Clin Pharmacol Ther 63 (1998): 397-402
  15. Ozdemir M, Aktan Y, Boydag BS, Cingi MI, Musmul A "Interaction between grapefruit juice and diazepam in humans." Eur J Drug Metab Pharmacokinet 23 (1998): 55-9
  16. Bailey DG, Malcolm J, Arnold O, Spence JD "Grapefruit juice-drug interactions." Br J Clin Pharmacol 46 (1998): 101-10
  17. Bailey DG, Kreeft JH, Munoz C, Freeman DJ, Bend JR "Grapefruit juice felodipine interaction: Effect of naringin and 6',7'-dihydroxybergamottin in humans." Clin Pharmacol Ther 64 (1998): 248-56
  18. Garg SK, Kumar N, Bhargava VK, Prabhakar SK "Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy." Clin Pharmacol Ther 64 (1998): 286-8
  19. Lilja JJ, Kivisto KT, Neuvonen PJ "Grapefruit juice-simvastatin interaction: Effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors." Clin Pharmacol Ther 64 (1998): 477-83
  20. Fuhr U, Maier-Bruggemann A, Blume H, et al. "Grapefruit juice increases oral nimodipine bioavailability." Int J Clin Pharmacol Ther 36 (1998): 126-32
  21. Lilja JJ, Kivisto KT, Neuvonen PJ "Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin." Clin Pharmacol Ther 66 (1999): 118-27
  22. Eagling VA, Profit L, Back DJ "Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-I protease inhibitor saquinavir by grapefruit juice components." Br J Clin Pharmacol 48 (1999): 543-52
  23. Damkier P, Hansen LL, Brosen K "Effect of diclofenac, disulfiram, itraconazole, grapefruit juice and erythromycin on the pharmacokinetics of quinidine." Br J Clin Pharmacol 48 (1999): 829-38
  24. Lee AJ, Chan WK, Harralson AF, Buffum J, Bui BCC "The effects of grapefruit juice on sertraline metabolism: An in vitro and in vivo study." Clin Ther 21 (1999): 1890-9
  25. Dresser GK, Spence JD, Bailey DG "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet 38 (2000): 41-57
  26. Gunston GD, Mehta U "Potentially serious drug interactions with grapefruit juice." S Afr Med J 90 (2000): 41
  27. Takanaga H, Ohnishi A, Maatsuo H, et al. "Pharmacokinetic analysis of felodipine-grapefruit juice interaction based on an irreversible enzyme inhibition model." Br J Clin Pharmacol 49 (2000): 49-58
  28. Libersa CC, Brique SA, Motte KB, et al. "Dramatic inhibition of amiodarone metabolism induced by grapefruit juice." Br J Clin Pharmacol 49 (2000): 373-8
  29. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther 68 (2000): 468-77
  30. Zaidenstein R, Soback S, Gips M, Avni B, Dishi V, Weissgarten Y, Golik A, Scapa E "Effect of grapefruit juice on the pharmacokinetics of losartan and its active metabolite E3174 in healthy volunteers." Ther Drug Monit 23 (2001): 369-73
  31. Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol 44 (1993): 295-8
  32. Flanagan D "Understanding the grapefruit-drug interaction." Gen Dent 53 (2005): 282-5; quiz 286

• alcohol

  Minor

  Metabolism

  The central nervous system effects and blood levels of ethanol may be increased in patients taking oral contraceptives, although data are lacking and reports are contradictory. The mechanism may be due to enzyme inhibition.

  What to do: Consider counseling women about this interaction which is unpredictable.

  1 source

  1. Hobbes J, Boutagy J, Shenfield GM "Interactions between ethanol and oral contraceptive steroids." Clin Pharmacol Ther 38 (1985): 371-80

• grapefruit juice

  Minor

  Metabolism

  Coadministration with grapefruit juice may increase the bioavailability of oral estrogens. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits.

  What to do: Coadministration with grapefruit juice may increase the bioavailability of oral estrogens. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits. In a small, randomized, crossover study, the administration of ethinyl estradiol with grapefruit juice (compared to herbal tea) increased peak plasma drug concentration (Cmax) by 37% and area under the concentration-time curve (AUC) by 28%. Based on these findings, grapefruit juice is unlikely to affect the overall safety profile of ethinyl estradiol. However, as with other drug interactions involving grapefruit juice, the pharmacokinetic alterations are subject to a high degree of interpatient variability. Also, the effect on other estrogens has not been studied.

  2 sources

  1. Weber A, Jager R, Borner A, et al. "Can grapefruit juice influence ethinyl estradiol bioavailability?" Contraception 53 (1996): 41-7
  2. Schubert W, Eriksson U, Edgar B, Cullberg G, Hedner T "Flavonoids in grapefruit juice inhibit the in vitro hepatic metabolism of 17B-estradiol." Eur J Drug Metab Pharmacokinet 20 (1995): 219-24

Conditions

Conditions in which Relugolix + Estradiol + Norethindrone needs care, as documented in this source.

• Abnormal Genital Bleeding

  Major

  The use of contraceptives is contraindicated when there is an undiagnosed abnormal genital bleeding. Adequate diagnostic measures should be undertaken to rule out the presence of any malignancy.

  3 sources

  1. "Product Information. Micronor (norethindrone)." Ortho McNeil Pharmaceutical (2001):
  2. "Product Information. Implanon (etonogestrel)." Organon Pharmaceuticals (2006):
  3. "Product Information. Liletta (levonorgestrel)." Actavis Pharma, Inc. (2016):

• Breast Neoplasms

  Major

  The use of progestogens is considered by manufacturers to be contraindicated in patients with existing or suspected malignancy of the breast. Some supportive data are available for medroxyprogesterone. Specifically, medroxyprogesterone treatment may be associated with breast cancer, primarily when the drug is administered intramuscularly. A pooled analysis of two case-control studies, one from the World Health Organization and the other from New Zealand, revealed a small overall relative risk of breast cancer in women who have ever used intramuscular medroxyprogesterone acetate. The relative risk was higher in the subgroup of women who had initiated therapy within the previous 5 years. Thus, an increased risk (approximately 2-fold) is associated with intramuscular medroxyprogesterone use in the first 5 years. A more recent U.S. study also found a statistically significant increase in breast cancer risk among recent users (defined as last use within the past five years) who used depo-medroxyprogesterone acetate for 12 months or longer.

  13 sources

  1. Liang AP, Levenson AG, Layde PM, Shelton JD, Hatcher RA, Potts M, Michelson MJ "Risk of breast, uterine corpus, and ovarian cancer in women receiving medroxyprogesterone injections." JAMA 249 (1983): 2909-12
  2. "Breast cancer, cervical cancer, and depot medroxyprogesterone acetate. WHO Collaborative Study of Neoplasia and Steroid Contraceptives" Lancet 2 (1984): 1207-8
  3. "Breast cancer and depot-medroxyprogesterone acetate: a multinational study. WHO Collaborative Study of Neoplasia and Steroid Contraceptives" Lancet 338 (1991): 833-8
  4. Jordan A "Toxicology of depot medroxyprogesterone acetate." Contraception 49 (1994): 189-201
  5. Chilvers C "Breast cancer and depot-medroxyprogesterone acetate - a review." Contraception 49 (1994): 211-22
  6. "Product Information. Depo-Provera (medroxyprogesterone)." Pharmacia and Upjohn (2001):
  7. "Product Information. Provera (medroxyprogesterone)." Pharmacia and Upjohn (2001):
  8. Skegg DC, Noonan EA, Paul C, Spears GF, Meirik O, Thomas DB "Depot medroxyprogesterone acetate and breast cancer." JAMA 273 (1995): 799-807

  Show all 13 sourcesShow fewer sources

  9. "Product Information. Norplant System (levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  10. "Product Information. Micronor (norethindrone)." Ortho McNeil Pharmaceutical (2001):
  11. "Product Information. Ovrette (norgestrel)." Wyeth-Ayerst Laboratories (2001):
  12. "Product Information. Prometrium (progesterone)." Virtus Pharmaceuticals LLC (2001):
  13. "Product Information. Implanon (etonogestrel)." Organon Pharmaceuticals (2006):

• Breast Neoplasms

  Major

  The use of estrogens is generally contraindicated in patients with known or suspected estrogen-dependent neoplasia such as breast and endometrial cancer, since it may stimulate tumor proliferation. High dosages of estrogens may be used for the palliative treatment of inoperable, metastatic breast cancer, but only in appropriately selected men and postmenopausal women.

  58 sources

  1. Ewertz M "Oral contraceptives and breast cancer risk in Denmark." Eur J Cancer 28A (1992): 1176-81
  2. Obrink A, Bunne G, Collen J, Tjernberg B "Endometrial cancer and exogenous estrogens." Acta Obstet Gynecol Scand 58 (1979): 123
  3. Palmer JR, Rosenberg L, Clarke EA, Miller DR, Shapiro S "Breast cancer risk after estrogen replacement therapy: results from the Toronto Breast Cancer Study." Am J Epidemiol 134 (1991): 1386-95
  4. Kaufman DW, Palmer JR, de Mouzon J, Rosenberg L, Stolley PD, Warshauer ME, Zauber AG, Shapiro S "Estrogen replacement therapy and the risk of breast cancer: results from the case-control surveillance study." Am J Epidemiol 134 (1991): 1375-85
  5. Spengler RF, Clarke EA, Woolever CA, Newman AM, Osborn RW "Exogenous estrogens and endometrial cancer: a case-control study and assessment of potential biases." Am J Epidemiol 114 (1981): 497-506
  6. Buring JE, Bain CJ, Ehrmann RL "Conjugated estrogen use and risk of endometrial cancer." Am J Epidemiol 124 (1986): 434-41
  7. Persson I, Adami HO, Bergkvist L, Lindgren A, Pettersson B, Hoover R, Schairer C "Risk of endometrial cancer after treatment with oestrogens alone or in conjunction with progestogens: results of a prospective study." BMJ 298 (1989): 147-51
  8. Hoover R, Glass A, Finkle WD, Azevedo D, Milne K "Conjugated estrogens and breast cancer risk in women." J Natl Cancer Inst 67 (1981): 815-20

  Show all 58 sourcesShow fewer sources

  9. Thomas DB, Persing JP, Hutchinson WB "Exogenous estrogens and other risk factors for breast cancer in women with benign breast diseases." J Natl Cancer Inst 69 (1982): 1017-25
  10. Antunes CM, Strolley PD, Rosenshein NB, Davies JL, Tonascia JA, Brown C, Burnett L, Rutledge A, Pokempner M, Garcia R "Endometrial cancer and estrogen use. Report of a large case-control study." N Engl J Med 300 (1979): 9-13
  11. Gordon J, Reagan JW, Finkle WD, Ziel HK "Estrogen and endometrial carcinoma. An independent pathology review supporting original risk estimate." N Engl J Med 297 (1977): 570-1
  12. Bergkvist L, Adami HO, Persson I, Hoover R, Schairer C "The risk of breast cancer after estrogen and estrogen-progestin replacement." N Engl J Med 321 (1989): 293-7
  13. Shapiro S, Kelly JP, Rosenberg L, Kaufman DW, Helmrich SP, Rosenshein NB, Lewis JL Jr, Knapp RC, Stolley PD, Schottenfeld D "Risk of localized and widespread endometrial cancer in relation to recent and discontinued use of conjugated estrogens." N Engl J Med 313 (1985): 969-72
  14. Gray LA Sr, Christopherson WM, Hoover RN "Estrogens and endometrial carcinoma." Obstet Gynecol 49 (1977): 385-9
  15. Delgado-Rodriguez M, Sillero-Arenas M, Martin-Moreno JM, Galvez-Vargas R "Oral contraceptives and cancer of the cervix uteri. A meta-analysis." Acta Obstet Gynecol Scand 71 (1992): 368-76
  16. Sillero-Arenas M, Rodriguez-Contreras R, Delgado-Rodriguez M, Bueno-Cavanillas A, Galvez-Vargas R "Patterns of research. Oral contraceptives and cervical cancer." Acta Obstet Gynecol Scand 70 (1991): 143-8
  17. Lund E "Oral contraceptives and breast cancer. A review with some comments on mathematical models." Acta Oncol 31 (1992): 183-6
  18. Miller DR, Rosenberg L, Kaufman DW, Stolley P, Warshauer ME, Shapiro S "Breast cancer before age 45 and oral contraceptive use: new findings." Am J Epidemiol 129 (1989): 269-80
  19. Rosenberg L, Palmer JR, Clarke EA, Shapiro S "A case-control study of the risk of breast cancer in relation to oral contraceptive use." Am J Epidemiol 136 (1992): 1437-44
  20. Schlesselman JJ "Oral contraceptives and breast cancer." Am J Obstet Gynecol 163 (1990): 1379-87
  21. Turnquest MA "Oral contraceptive use and incidence of cervical intraepithelial neoplasia." Am J Obstet Gynecol 168 (1993): 1895-6
  22. Kaunitz AM "Oral contraceptives and gynecologic cancer: an update for the 1990s." Am J Obstet Gynecol 167 (1992): 1171-6
  23. Romieu I, Willett WC, Colditz GA, Stampfer MJ, Rosner B, Hennekens CH, Speizer FE "Prospective study of oral contraceptive use and risk of breast cancer in women." J Natl Cancer Inst 81 (1989): 1313-21
  24. Olsson H, Moller TR, Ranstam J "Early oral contraceptive use and breast cancer among premenopausal women: final report from a study in southern Sweden." J Natl Cancer Inst 81 (1989): 1000-4
  25. Jones MW, Silverberg SG "Cervical adenocarcinoma in young women: possible relationship to microglandular hyperplasia and use of oral contraceptives." Obstet Gynecol 73 (1989): 984-9
  26. Murray PP, Stadel BV, Schlesselman JJ "Oral contraceptive use in women with a family history of breast cancer." Obstet Gynecol 73 (1989): 977-83
  27. Thomas DB "Oral contraceptives and breast cancer: review of the epidemiologic literature." Contraception 43 (1991): 597-642
  28. Brinton LA "Oral contraceptives and cervical neoplasia." Contraception 43 (1991): 581-95
  29. "Oral contraceptives and neoplasia. WHO Scientific Group." World Health Organ Tech Rep Ser 817 (1992): 1-46
  30. Woodruff JD, Pickar JH "Incidence of endometrial hyperplasia in postmenopausal women taking conjugated estrogens (Premarin) with medroxyprogesterone acetate or conjugated estrogens alone." Am J Obstet Gynecol 170 (1994): 1213-23
  31. Mishell DR "Contraception." N Engl J Med 320 (1989): 777-85
  32. "Product Information. Premarin (conjugated estrogens)." Wyeth-Ayerst Laboratories (2001):
  33. Lavecchia C, Negri E, Franceschi S, Talamini R, Amadori D, Filiberti R, Conti E, Montella M, Veronesi A, Parazzini F, Ferraroni M "Oral contraceptives and breast cancer: a cooperative italian study." Int J Cancer 60 (1995): 163-7
  34. Colditz GA, Hankinson SE, Hunter DJ, et al. "The use of estrogens and progestins and the risk of breast cancer in postmenopausal women." N Engl J Med 332 (1995): 1589-93
  35. Stanford JL, Weiss NS, Voigt LF, Daling JR, Habel LA, Rossing MA "Combined estrogen and progestin hormone replacement therapy in relation to risk of breast cancer in middle-aged women." JAMA 274 (1995): 137-42
  36. "Product Information. Climara (estradiol)." Berlex Laboratories (2001):
  37. "Product Information. Estrace (estradiol)." Warner Chilcott Laboratories (2001):
  38. "Product Information. Estraderm (estradiol)." Ciba-Geigy Pharmaceuticals (2001):
  39. "Product Information. Vivelle (estradiol)." Ciba-Geigy Pharmaceuticals (2001):
  40. The Writing Group for the PEPI Trial "Effects of hormone replacement therapy on endometrial histology in postmenopausal women." JAMA 275 (1996): 370-5
  41. Zondervan KT, Carpenter LM, Painter R, Vessey MP "Oral contraceptives and cervical cancer - further findings from the oxford family planning association contraceptive study." Br J Cancer 73 (1996): 1291-7
  42. Calle EE, Heath CW, Miraclemcmahill HL, Coates RJ, Liff JM, Franceschi S, Talamini R, Chantarakul N, Koetsawang S, Rachawat D "Breast cancer and hormonal contraceptives: further results." Contraception 54 (suppl (1996): s1-106
  43. Rettig BA, Lemon HM "Cancers related to contraceptive use." Br J Cancer 74 (1996): 1509-10
  44. "Product Information. Ortho-Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho McNeil Pharmaceutical
  45. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho McNeil Pharmaceutical (2001):
  46. "Product Information. Demulen 1/50 (ethinyl estradiol-ethynodiol)." Searle
  47. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  48. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho McNeil Pharmaceutical (2001):
  49. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories (2001):
  50. "Product Information. Ortho-Novum 1/50 (mestranol-norethindrone)." Ortho McNeil Pharmaceutical
  51. "Product Information. Ortho-Est (estropipate)." Ortho McNeil Pharmaceutical (2001):
  52. Greendale GA, Reboussin BA, Sie A, et al. "Effects of estrogen and estrogen-progestin on mammographic parenchymal density." Ann Intern Med 130 (1999): 262-9
  53. Gapstur SM, Morrow M, Sellers TA "Hormone replacement therapy and risk of breast cancer with a favorable histology: results of the Iowa women's health study." JAMA 281 (1999): 2091-7
  54. "Product Information. Ortho Dienestrol (dienestrol topical)." Ortho McNeil Pharmaceutical
  55. "Product Information. Ogen (estropipate topical)." Pharmacia and Upjohn (2001):
  56. "Product Information. Estinyl (ethinyl estradiol)." Schering Corporation
  57. "Product Information. Estratab (esterified estrogens)." Solvay Pharmaceuticals Inc (2001):
  58. "Product Information. Nextstellis (drospirenone-estetrol)." Mayne Pharma (2021):

• Breast Neoplasms

  Major

  When treated with an estrogen, patients with breast cancer and bone metastases may develop severe hypercalcemia, in which case the drug should be stopped and measures be taken to reduce serum calcium levels.

  11 sources

  1. "Product Information. Premarin (conjugated estrogens)." Wyeth-Ayerst Laboratories (2001):
  2. "Product Information. Climara (estradiol)." Berlex Laboratories (2001):
  3. "Product Information. Estrace (estradiol)." Warner Chilcott Laboratories (2001):
  4. "Product Information. Estraderm (estradiol)." Ciba-Geigy Pharmaceuticals (2001):
  5. "Product Information. Vivelle (estradiol)." Ciba-Geigy Pharmaceuticals (2001):
  6. "Product Information. Emcyt (estramustine)." Pharmacia and Upjohn (2001):
  7. "Product Information. Ortho-Est (estropipate)." Ortho McNeil Pharmaceutical (2001):
  8. "Product Information. Ortho Dienestrol (dienestrol topical)." Ortho McNeil Pharmaceutical

  Show all 11 sourcesShow fewer sources

  9. "Product Information. Ogen (estropipate topical)." Pharmacia and Upjohn (2001):
  10. "Product Information. Estinyl (ethinyl estradiol)." Schering Corporation
  11. "Product Information. Estratab (esterified estrogens)." Solvay Pharmaceuticals Inc (2001):

• Hypertension

  Major

  The risk of myocardial infarction and strokes, including those associated with oral contraceptive use and some estrogen use, is increased in patients with hypertension. Moreover, estrogens (and progestogens) may elevate blood pressure and worsen the hypertension, thus compounding the risk. Clinically significant blood pressure increases have been reported during estrogen therapy, particularly in patients receiving high dosages or treated with oral contraceptive combinations having high progestational activity. These effects also increase with duration of therapy and patient age. Therapy with estrogens should be administered cautiously in patients with preexisting hypertension. Patients should be monitored for changes in cardiovascular status, and their antihypertensive regimen adjusted or estrogen therapy withdrawn as necessary. In patients requiring contraception, alternative methods should be considered for those who are hypertensive, over age 35, and smoke.

  53 sources

  1. Leiman G "Depo-medroxyprogesterone acetate as a contraceptive agent: its effect on weight and blood pressure." Am J Obstet Gynecol 114 (1972): 97-102
  2. Williams RS "Benefits and risks of oral contraceptive use." Postgrad Med 92 (1992): 155-7
  3. Crane MG, Harris JJ "Estrogens and hypertension: effect of discontinuing estrogens on blood pressure, exchangeable sodium, and the renin-aldosterone system." Am J Med Sci 276 (1978): 33-55
  4. Crane MG, Harris JJ, Winsor W 3d "Hypertension, oral contraceptive agents, and conjugated estrogens." Ann Intern Med 74 (1971): 13-21
  5. Rosenberg L, Slone D, Shapiro S, Kaufman D, Stolley PD, Miettinen OS "Noncontraceptive estrogens and myocardial infarction in young women." JAMA 244 (1980): 339-42
  6. Jick H, Dinan B, Rothman KJ "Noncontraceptive estrogens and nonfatal myocardial infarction." JAMA 239 (1978): 1407-8
  7. Wren BG, Routledge DA "Blood pressure changes: oestrogens in climacteric women." Med J Aust 2 (1981): 528-31
  8. Rosenberg L, Palmer JR, Lesko SM, Shapiro S "Oral contraceptive use and the risk of myocardial infarction." Am J Epidemiol 131 (1990): 1009-16

  Show all 53 sourcesShow fewer sources

  9. Thorogood M, Mann J, Murphy M, Vessey M "Fatal stroke and use of oral contraceptives: findings from a case- control study." Am J Epidemiol 136 (1992): 35-45
  10. Leaf DA, Bland D, Schaad D, Neighbor WE, Scott CS "Oral contraceptive use and coronary risk factors in women." Am J Med Sci 301 (1991): 365-8
  11. Thorneycroft IH "Oral contraceptives and myocardial infarction." Am J Obstet Gynecol 163 (1990): 1393-7
  12. Lidegaard O "Oral contraception and risk of a cerebral thromboembolic attack: results of a case-control study." BMJ 306 (1993): 956-63
  13. Derman RJ "Oral contraceptives and cardiovascular risk. Taking a safe course of action." Postgrad Med 88 (1990): 119-22
  14. Hannaford PC, Croft PR, Kay CR "Oral contraception and stroke. Evidence from the Royal College of General Practitioners' Oral Contraception Study." Stroke 25 (1994): 935-42
  15. Steinberg WM "Oral contraception: risks and benefits." Adv Contracept 5 (1989): 219-28
  16. Peterson HB, Lee NC "Long-term health risks and benefits of oral contraceptive use." Obstet Gynecol Clin North Am 17 (1990): 775-88
  17. Derman R "Oral contraceptives: a reassessment." Obstet Gynecol Surv 44 (1989): 662-8
  18. Belchetz PE "Hormonal treatment of postmenopausal women." N Engl J Med 330 (1994): 1062-71
  19. Stampfer MJ, Colditz GA, Willett WC, et al. "Postmenopausal estrogen and cardiovascular disease. Ten-year follow-up from the Nurses' Health Study." N Engl J Med 325 (1991): 756-62
  20. Barrett-Connor E, Bush TL "Estrogen and coronary heart disease in women." JAMA 265 (1991): 1861-7
  21. Barrett-Connor E, Wingard DL, Criqui MH "Postmenopausal estrogen use and heart disease risk factors in the 1980s. Rancho Bernardo, Calif, revisited." JAMA 261 (1989): 1095-2100
  22. Mishell DR "Contraception." N Engl J Med 320 (1989): 777-85
  23. "Product Information. Premarin (conjugated estrogens)." Wyeth-Ayerst Laboratories (2001):
  24. Schwartz J, Freeman R, Frishman W "Clinical pharmacology of estrogens: cardiovascular actions and cardioprotective benefits of replacement therapy in postmenopausal women." J Clin Pharmacol 35 (1995): 1-16
  25. The Writing Group for the PEPI Trial "Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women: the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial." JAMA 273 (1995): 199-208
  26. "Product Information. Climara (estradiol)." Berlex Laboratories (2001):
  27. "Product Information. Estrace (estradiol)." Warner Chilcott Laboratories (2001):
  28. "Product Information. Estraderm (estradiol)." Ciba-Geigy Pharmaceuticals (2001):
  29. "Product Information. Vivelle (estradiol)." Ciba-Geigy Pharmaceuticals (2001):
  30. Norris LA, Bonnar J "The effect of oestrogen dose and progestogen type on haemostatic changes in women taking low dose oral contraceptives." Br J Obstet Gynaecol 103 (1996): 261-7
  31. Levine AB, Teppa J, Mcgough B, Cowchock FS "Evaluation of the prethrombotic state in pregnancy and in women using oral contraceptives." Contraception 53 (1996): 255-7
  32. Petitti DB, Sidney S, Bernstein A, Wolf S, Quesenberry C, Ziel HK "Stroke in users of low-dose oral contraceptives." N Engl J Med 335 (1996): 8-15
  33. Speroff L "Oral contraceptives and venous thromboembolism." Int J Gynaecol Obstet 54 (1996): 45-50
  34. Poulter NR, Chang CL, Farley TMM, Meirik O, Marmot MG, Debertribeiro M, Medina E, Artigas J, Shen H, Zhong YH, Zhang DW, "Ischaemic stroke and combined oral contraceptives: results of an international, multicentre, case-control study." Lancet 348 (1996): 498-505
  35. Poulter NR, Chang CL, Farley TMM, Meirik O, Marmot MG "Haemorrhagic stroke, overall stroke risk, and combined oral contraceptives: results of an international, multicentre, case-control study." Lancet 348 (1996): 505-10
  36. Piegsa K, Guillebaud J "Oral contraceptives and the risk of DVT." Practitioner 240 (1996): 544
  37. Martinelli I, Rosendaal FR, Vandenbroucke JP, Mannucci PM "Oral contraceptives are a risk factor for cerebral vein thrombosis." Thromb Haemost 76 (1996): 477-8
  38. Farley TMM, Meirik O, Poulter NR, Chang CL, Marmot MG "Oral contraceptives and thrombotic diseases: impact of new epidemiological studies." Contraception 54 (1996): 193-5
  39. "Product Information. Ortho-Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho McNeil Pharmaceutical
  40. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho McNeil Pharmaceutical (2001):
  41. "Product Information. Demulen 1/50 (ethinyl estradiol-ethynodiol)." Searle
  42. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  43. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho McNeil Pharmaceutical (2001):
  44. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories (2001):
  45. "Product Information. Ortho-Novum 1/50 (mestranol-norethindrone)." Ortho McNeil Pharmaceutical
  46. Sidney S, Petitti DB, Quesenberry CP "Myocardial infarction and the use of estrogen and estrogen-progestogen in postmenopausal women." Ann Intern Med 127 (1997): 501-8
  47. "Product Information. Ortho-Est (estropipate)." Ortho McNeil Pharmaceutical (2001):
  48. Thorogood M "Risk of stroke in users of oral contraceptives." JAMA 281 (1999): 1255-6
  49. "Product Information. Ortho Dienestrol (dienestrol topical)." Ortho McNeil Pharmaceutical
  50. "Product Information. Ogen (estropipate topical)." Pharmacia and Upjohn (2001):
  51. "Product Information. Estinyl (ethinyl estradiol)." Schering Corporation
  52. "Product Information. Estratab (esterified estrogens)." Solvay Pharmaceuticals Inc (2001):
  53. "Product Information. Nextstellis (drospirenone-estetrol)." Mayne Pharma (2021):

• Liver Diseases

  Major

  The use of progestogens, in general, is contraindicated in patients with impaired hepatic function or liver disease. There are little or no data concerning the pharmacokinetic disposition of the different progestogens in patients with hepatic disease. However, most hormones, including progestational hormones, are known to be extensively metabolized by the liver. Medroxyprogesterone should not be used by women with significant liver disease and should be discontinued if jaundice or disturbances of liver function occur.

  12 sources

  1. Utaaker E, Lundgren S, Kvinnsland S, Aakvaag A "Pharmacokinetics and metabolism of medroxyprogesterone acetate in patients with advanced breast cancer." J Steroid Biochem 31 (1988): 437-41
  2. Castegnaro E, Sala G "Pharmacokinetics and metabolism of medroxyprogesterone acetate. Influence of the route of administration and of its physical state." Steroidologia 2 (1971): 13-26
  3. Riippa P, Kauppila A, Sundstrom H, Vihko R "Hepatic impairment during simultaneous administration of medroxyprogesterone acetate and tamoxifen in the treatment of endometrial and ovarian carcinoma." Anticancer Res 4 (1984): 109-12
  4. Meyer WJ, 3d Wiener I, Emory LE, Cole CM, Isenberg N, Fagan CJ, Thompson JC "Cholelithiasis associated with medroxyprogesterone acetate therapy in men." Res Commun Chem Pathol Pharmacol 75 (1992): 69-84
  5. Hendeles SM, Galand N, Schwers J "Metabolism of orally administered D-norgestrel in women." Acta Endocrinol (Copenh) 71 (1972): 557-68
  6. "Product Information. Depo-Provera (medroxyprogesterone)." Pharmacia and Upjohn (2001):
  7. "Product Information. Provera (medroxyprogesterone)." Pharmacia and Upjohn (2001):
  8. "Product Information. Norplant System (levonorgestrel)." Wyeth-Ayerst Laboratories (2001):

  Show all 12 sourcesShow fewer sources

  9. "Product Information. Micronor (norethindrone)." Ortho McNeil Pharmaceutical (2001):
  10. "Product Information. Ovrette (norgestrel)." Wyeth-Ayerst Laboratories (2001):
  11. "Product Information. Prometrium (progesterone)." Virtus Pharmaceuticals LLC (2001):
  12. "Product Information. Implanon (etonogestrel)." Organon Pharmaceuticals (2006):

• Liver Neoplasms

  Major

  The use of oral contraceptives is contraindicated in patients with liver tumors. An increased risk of benign hepatic adenomas and hepatocellular carcinomas has been associated with long-term, oral estrogen- progestin contraceptive use of at least 4 years and 8 years, respectively. Although these tumors are rare and have not been reported with other types of estrogen or progestogen therapies, any preparation containing estrogens and/or progestogens should probably be avoided in patients with existing tumors of the liver. Hepatic hemangiomas and nodular hyperplasia of the liver have been reported with isolated estrogen therapy.

  34 sources

  1. Tao LC "Oral contraceptive-associated liver cell adenoma and hepatocellular carcinoma." Cancer 68 (1991): 341-7
  2. "Depot-medroxyprogesterone acetate (DMPA) and risk of liver cancer. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives." Int J Cancer 49 (1991): 182-5
  3. Conter RL, Longmire WP Jr "Recurrent hepatic hemangiomas. Possible association with estrogen therapy." Ann Surg 207 (1988): 115-9
  4. Aldinger K, Ben-Menachem Y, Whalen G "Focal nodular hyperplasia of the liver associated with high-dosage estrogens." Arch Intern Med 137 (1977): 357-9
  5. Palmer JR, Rosenberg L, Kaufman DW, Warshauer ME, Stolley P, Shapiro S "Oral contraceptive use and liver cancer." Am J Epidemiol 130 (1989): 878-82
  6. Mooney MJ, Nyreen MR, Hall RA, Carter PL "Hepatic adenoma presenting as a right lower quadrant mass." Am Surg 59 (1993): 229-31
  7. Gyorffy EJ, Bredfeldt JE, Black WC "Transformation of hepatic cell adenoma to hepatocellular carcinoma due to oral contraceptive use." Ann Intern Med 110 (1989): 489-90
  8. Tavani A, Negri E, Parazzini F, Franceschi S, La Vecchia C "Female hormone utilisation and risk of hepatocellular carcinoma." Br J Cancer 67 (1993): 635-7

  Show all 34 sourcesShow fewer sources

  9. Mathieu D, Zafrani ES, Anglade MC, Dhumeaux D "Association of focal nodular hyperplasia and hepatic hemangioma." Gastroenterology 97 (1989): 154-7
  10. Le Bail B, Jouhanole H, Deugnier Y, Salame G, Pellegrin JL, Saric J, Balabaud C, Bioulac-Sage P "Liver adenomatosis with granulomas in two patients on long-term oral contraceptives." Am J Surg Pathol 16 (1992): 982-7
  11. "Oral contraceptives and neoplasia. WHO Scientific Group." World Health Organ Tech Rep Ser 817 (1992): 1-46
  12. Mishell DR "Contraception." N Engl J Med 320 (1989): 777-85
  13. "Product Information. Premarin (conjugated estrogens)." Wyeth-Ayerst Laboratories (2001):
  14. "Product Information. Climara (estradiol)." Berlex Laboratories (2001):
  15. "Product Information. Estrace (estradiol)." Warner Chilcott Laboratories (2001):
  16. "Product Information. Estraderm (estradiol)." Ciba-Geigy Pharmaceuticals (2001):
  17. "Product Information. Vivelle (estradiol)." Ciba-Geigy Pharmaceuticals (2001):
  18. "Product Information. Ortho-Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho McNeil Pharmaceutical
  19. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho McNeil Pharmaceutical (2001):
  20. "Product Information. Demulen 1/50 (ethinyl estradiol-ethynodiol)." Searle
  21. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  22. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho McNeil Pharmaceutical (2001):
  23. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories (2001):
  24. "Product Information. Ortho-Novum 1/50 (mestranol-norethindrone)." Ortho McNeil Pharmaceutical
  25. "Product Information. Ortho-Est (estropipate)." Ortho McNeil Pharmaceutical (2001):
  26. "Product Information. Ortho Dienestrol (dienestrol topical)." Ortho McNeil Pharmaceutical
  27. "Product Information. Ogen (estropipate topical)." Pharmacia and Upjohn (2001):
  28. "Product Information. Estinyl (ethinyl estradiol)." Schering Corporation
  29. "Product Information. Estratab (esterified estrogens)." Solvay Pharmaceuticals Inc (2001):
  30. "Product Information. Norplant System (levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  31. "Product Information. Micronor (norethindrone)." Ortho McNeil Pharmaceutical (2001):
  32. "Product Information. Ovrette (norgestrel)." Wyeth-Ayerst Laboratories (2001):
  33. "Product Information. Implanon (etonogestrel)." Organon Pharmaceuticals (2006):
  34. "Product Information. Nextstellis (drospirenone-estetrol)." Mayne Pharma (2021):

• Liver Neoplasms

  Major

  The use of oral contraceptives is contraindicated in patients with liver tumors. An increased risk of benign hepatic adenomas and hepatocellular carcinomas has been associated with long-term, oral estrogen- progestin contraceptive use of at least 4 years and 8 years, respectively. Although these tumors are rare and have not been reported with other types of estrogen or progestogen therapies, any preparation containing estrogens and/or progestogens should probably be avoided in patients with existing tumors of the liver. Hepatic hemangiomas and nodular hyperplasia of the liver have been reported with isolated estrogen therapy.

  34 sources

  1. Tao LC "Oral contraceptive-associated liver cell adenoma and hepatocellular carcinoma." Cancer 68 (1991): 341-7
  2. "Depot-medroxyprogesterone acetate (DMPA) and risk of liver cancer. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives." Int J Cancer 49 (1991): 182-5
  3. Conter RL, Longmire WP Jr "Recurrent hepatic hemangiomas. Possible association with estrogen therapy." Ann Surg 207 (1988): 115-9
  4. Aldinger K, Ben-Menachem Y, Whalen G "Focal nodular hyperplasia of the liver associated with high-dosage estrogens." Arch Intern Med 137 (1977): 357-9
  5. Palmer JR, Rosenberg L, Kaufman DW, Warshauer ME, Stolley P, Shapiro S "Oral contraceptive use and liver cancer." Am J Epidemiol 130 (1989): 878-82
  6. Mooney MJ, Nyreen MR, Hall RA, Carter PL "Hepatic adenoma presenting as a right lower quadrant mass." Am Surg 59 (1993): 229-31
  7. Gyorffy EJ, Bredfeldt JE, Black WC "Transformation of hepatic cell adenoma to hepatocellular carcinoma due to oral contraceptive use." Ann Intern Med 110 (1989): 489-90
  8. Tavani A, Negri E, Parazzini F, Franceschi S, La Vecchia C "Female hormone utilisation and risk of hepatocellular carcinoma." Br J Cancer 67 (1993): 635-7

  Show all 34 sourcesShow fewer sources

  9. Mathieu D, Zafrani ES, Anglade MC, Dhumeaux D "Association of focal nodular hyperplasia and hepatic hemangioma." Gastroenterology 97 (1989): 154-7
  10. Le Bail B, Jouhanole H, Deugnier Y, Salame G, Pellegrin JL, Saric J, Balabaud C, Bioulac-Sage P "Liver adenomatosis with granulomas in two patients on long-term oral contraceptives." Am J Surg Pathol 16 (1992): 982-7
  11. "Oral contraceptives and neoplasia. WHO Scientific Group." World Health Organ Tech Rep Ser 817 (1992): 1-46
  12. Mishell DR "Contraception." N Engl J Med 320 (1989): 777-85
  13. "Product Information. Premarin (conjugated estrogens)." Wyeth-Ayerst Laboratories (2001):
  14. "Product Information. Climara (estradiol)." Berlex Laboratories (2001):
  15. "Product Information. Estrace (estradiol)." Warner Chilcott Laboratories (2001):
  16. "Product Information. Estraderm (estradiol)." Ciba-Geigy Pharmaceuticals (2001):
  17. "Product Information. Vivelle (estradiol)." Ciba-Geigy Pharmaceuticals (2001):
  18. "Product Information. Ortho-Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho McNeil Pharmaceutical
  19. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho McNeil Pharmaceutical (2001):
  20. "Product Information. Demulen 1/50 (ethinyl estradiol-ethynodiol)." Searle
  21. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  22. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho McNeil Pharmaceutical (2001):
  23. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories (2001):
  24. "Product Information. Ortho-Novum 1/50 (mestranol-norethindrone)." Ortho McNeil Pharmaceutical
  25. "Product Information. Ortho-Est (estropipate)." Ortho McNeil Pharmaceutical (2001):
  26. "Product Information. Ortho Dienestrol (dienestrol topical)." Ortho McNeil Pharmaceutical
  27. "Product Information. Ogen (estropipate topical)." Pharmacia and Upjohn (2001):
  28. "Product Information. Estinyl (ethinyl estradiol)." Schering Corporation
  29. "Product Information. Estratab (esterified estrogens)." Solvay Pharmaceuticals Inc (2001):
  30. "Product Information. Norplant System (levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  31. "Product Information. Micronor (norethindrone)." Ortho McNeil Pharmaceutical (2001):
  32. "Product Information. Ovrette (norgestrel)." Wyeth-Ayerst Laboratories (2001):
  33. "Product Information. Implanon (etonogestrel)." Organon Pharmaceuticals (2006):
  34. "Product Information. Nextstellis (drospirenone-estetrol)." Mayne Pharma (2021):

• Osteoporosis

  Major

  Relugolix is contraindicated for use in women with known osteoporosis because of the risk of further bone loss. Prior to initiating therapy, an assessment of bone mineral density by dual-energy X-ray absorptiometry (DXA) is recommended. Carefully consider the risks of treatment in women with a history of a low trauma fracture or risk factors for osteoporosis. Treatment should be limited to 24 months due to risk of continued bone loss which may not be reversible.

  1 source

  1. "Product Information. Myfembree (estradiol/norethindrone/relugolix)." Myovant Sciences, Inc. (2021):

• Thromboembolism

  Major

  The use of progestogens, in general, is considered by manufacturers to be contraindicated in patients with active thrombophlebitis, cerebrovascular disease, or a current or past history of thromboembolic disorders. While the role of progestogens in the development of thromboembolic events associated with hormonal therapy is often unclear and thought to be secondary to that of estrogens, it may not be insignificant. Medroxyprogesterone, a common progestational agent, has been shown to produce a hypercoagulable state in high dosages. Whether or not this effect contributes to the development of thrombotic events is unknown. However, thrombophlebitis and pulmonary embolism have been reported with megestrol, an antineoplastic and progestational agent. In addition, an increased risk of nonfatal venous thrombosis has been associated with oral contraceptive combinations containing desogestrel or gestodene relative to those that contain other progestins (e.g., levonorgestrel, norethindrone), suggesting some degree of hemostatic effect by progestogens.

  17 sources

  1. Astedt B, Jeppsson S, Pandolfi M "Fibrinolytic activity of veins during use of depot medroxyprogesterone acetate as a contraceptive." Fertil Steril 23 (1972): 489-92
  2. Yamamoto H, Noguchi S, Miyauchi K, Inaji H, Imaoka S, Koyama H, Iwanaga T "Changes in hematologic parameters during treatment with medroxyprogesterone acetate for breast cancer." Jpn J Cancer Res 82 (1991): 420-5
  3. Fukutomi T, Nanasawa T, Yamamoto H, Adachi I, Watanabe T "The induction of a hypercoagulable state by medroxyprogesterone acetate in breast cancer patients." Jpn J Surg 20 (1990): 665-70
  4. "Product Information. Depo-Provera (medroxyprogesterone)." Pharmacia and Upjohn (2001):
  5. "Product Information. Provera (medroxyprogesterone)." Pharmacia and Upjohn (2001):
  6. "Product Information. Ortho-Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho McNeil Pharmaceutical
  7. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho McNeil Pharmaceutical (2001):
  8. "Product Information. Demulen 1/50 (ethinyl estradiol-ethynodiol)." Searle

  Show all 17 sourcesShow fewer sources

  9. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  10. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho McNeil Pharmaceutical (2001):
  11. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories (2001):
  12. "Product Information. Megace (megestrol)." Bristol-Myers Squibb (2001):
  13. "Product Information. Norplant System (levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  14. "Product Information. Micronor (norethindrone)." Ortho McNeil Pharmaceutical (2001):
  15. "Product Information. Ovrette (norgestrel)." Wyeth-Ayerst Laboratories (2001):
  16. "Product Information. Prometrium (progesterone)." Virtus Pharmaceuticals LLC (2001):
  17. "Product Information. Implanon (etonogestrel)." Organon Pharmaceuticals (2006):

• Thromboembolism

  Major

  The use of estrogens is considered by manufacturers and some authorities to be contraindicated in patients with active thrombotic or thromboembolic disorders. The use of estrogen-containing oral contraceptives is additionally deemed contraindicated in patients with a history of such disorders and/or current cerebrovascular or coronary artery disease. Females with a history of migraines with aura are at an increased risk for stroke and this stroke risk may be further increased in females who have migraines with aura with use of combination oral contraceptives. Hypercoagulability and changes in various clotting factors and blood components have been observed in women receiving estrogen therapy. Although the clinical significance of these effects is unknown, epidemiological data suggest it may be dose-dependent. The risk is probably slight with the use of newer, low-dose oral contraceptives in the absence of known risk factors (e.g., smoker, particularly over the age of 35; hypertension; hyperlipidemia; obesity; diabetes; age over 40). However, a much more significant risk has been reported with higher dosages, such as those used to treat prostate or metastatic breast cancer or those used in older formulations of birth control pills. Therapy with estrogens should be administered cautiously in the lowest effective dosage and only after careful consideration of risks and benefits. Estrogens should be avoided in patients with a history of thrombotic and thromboembolic disorders associated with estrogen use, except when used in the treatment of breast or prostatic malignancy.

  61 sources

  1. Notelovitz M "Oral contraception and coagulation." Clin Obstet Gynecol 28 (1985): 73-83
  2. Meade TW "Oral contraceptives, clotting factors, and thrombosis." Am J Obstet Gynecol 142 (1982): 758-61
  3. Williams RS "Benefits and risks of oral contraceptive use." Postgrad Med 92 (1992): 155-7
  4. Rosenberg L, Slone D, Shapiro S, Kaufman D, Stolley PD, Miettinen OS "Noncontraceptive estrogens and myocardial infarction in young women." JAMA 244 (1980): 339-42
  5. Jick H, Dinan B, Rothman KJ "Noncontraceptive estrogens and nonfatal myocardial infarction." JAMA 239 (1978): 1407-8
  6. Boschetti C, Cortellaro M, Nencioni T, Bertolli V, Della Volpe A, Zanussi C "Short- and long-term effects of hormone replacement therapy (transdermal estradiol vs oral conjugated equine estrogens, combined with medroxyprogesterone acetate) on blood coagulation factors in postmenopausal women." Thromb Res 62 (1991): 1-8
  7. Rosenberg L, Palmer JR, Lesko SM, Shapiro S "Oral contraceptive use and the risk of myocardial infarction." Am J Epidemiol 131 (1990): 1009-16
  8. Thorogood M, Mann J, Murphy M, Vessey M "Fatal stroke and use of oral contraceptives: findings from a case- control study." Am J Epidemiol 136 (1992): 35-45

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  9. Leaf DA, Bland D, Schaad D, Neighbor WE, Scott CS "Oral contraceptive use and coronary risk factors in women." Am J Med Sci 301 (1991): 365-8
  10. Thorneycroft IH "Oral contraceptives and myocardial infarction." Am J Obstet Gynecol 163 (1990): 1393-7
  11. Lidegaard O "Oral contraception and risk of a cerebral thromboembolic attack: results of a case-control study." BMJ 306 (1993): 956-63
  12. Derman RJ "Oral contraceptives and cardiovascular risk. Taking a safe course of action." Postgrad Med 88 (1990): 119-22
  13. Hannaford PC, Croft PR, Kay CR "Oral contraception and stroke. Evidence from the Royal College of General Practitioners' Oral Contraception Study." Stroke 25 (1994): 935-42
  14. Steinberg WM "Oral contraception: risks and benefits." Adv Contracept 5 (1989): 219-28
  15. Miwa LJ, Edmunds AL, Shaefer MS, Raynor SC "Idiopathic thromboembolism associated with triphasic oral contraceptives." DICP 23 (1989): 773-5
  16. Beaumont V, Lemort N, Beaumont JL "Oral contraceptives, sex steroid-induced antibodies and vascular thrombosis: results from 1318 cases." Eur Heart J 12 (1991): 1219-24
  17. Key JD, Hammill WW, Everett L "Pulmonary embolus in an adolescent on oral contraceptives." J Adolesc Health 13 (1992): 713-5
  18. Burkman RT Jr "Benefits and risk of oral contraceptives. A reassessment." J Reprod Med 36 (1991): 217-8
  19. Peterson HB, Lee NC "Long-term health risks and benefits of oral contraceptive use." Obstet Gynecol Clin North Am 17 (1990): 775-88
  20. Boston Collaborative Drug Surveilance Program "Surgically confirmed gallbladder disease, venous thromboembolism, and breast tumors in relation to postmenopausal estrogen therapy." N Engl J Med 290 (1974): 15-9
  21. Belchetz PE "Hormonal treatment of postmenopausal women." N Engl J Med 330 (1994): 1062-71
  22. Devor M, Barrett-Connor E, Renvall M, Feigal D, Ramsdell J "Estrogen replacement therapy and the risk of venous thrombosis." Am J Med 92 (1992): 275-81
  23. Barrett-Connor E, Bush TL "Estrogen and coronary heart disease in women." JAMA 265 (1991): 1861-7
  24. Grady D, Rubin SM, Petiti DB, et al. "Hormone therapy to prevent disease and prolong life in postmenopausal women." Ann Intern Med 117 (1992): 1016-36
  25. Barrett-Connor E, Wingard DL, Criqui MH "Postmenopausal estrogen use and heart disease risk factors in the 1980s. Rancho Bernardo, Calif, revisited." JAMA 261 (1989): 1095-2100
  26. Mishell DR "Contraception." N Engl J Med 320 (1989): 777-85
  27. "Product Information. Premarin (conjugated estrogens)." Wyeth-Ayerst Laboratories (2001):
  28. Schwartz J, Freeman R, Frishman W "Clinical pharmacology of estrogens: cardiovascular actions and cardioprotective benefits of replacement therapy in postmenopausal women." J Clin Pharmacol 35 (1995): 1-16
  29. Lidegaard O "Oral contraceptives, pregnancy and the risk of cerebral thromboembolism: the influence of diabetes, hypertension, migraine and previous thrombotic disease." Br J Obstet Gynaecol 102 (1995): 153-9
  30. The Writing Group for the PEPI Trial "Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women: the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial." JAMA 273 (1995): 199-208
  31. "Product Information. Climara (estradiol)." Berlex Laboratories (2001):
  32. "Product Information. Estrace (estradiol)." Warner Chilcott Laboratories (2001):
  33. "Product Information. Estraderm (estradiol)." Ciba-Geigy Pharmaceuticals (2001):
  34. "Product Information. Vivelle (estradiol)." Ciba-Geigy Pharmaceuticals (2001):
  35. Norris LA, Bonnar J "The effect of oestrogen dose and progestogen type on haemostatic changes in women taking low dose oral contraceptives." Br J Obstet Gynaecol 103 (1996): 261-7
  36. Levine AB, Teppa J, Mcgough B, Cowchock FS "Evaluation of the prethrombotic state in pregnancy and in women using oral contraceptives." Contraception 53 (1996): 255-7
  37. Petitti DB, Sidney S, Bernstein A, Wolf S, Quesenberry C, Ziel HK "Stroke in users of low-dose oral contraceptives." N Engl J Med 335 (1996): 8-15
  38. Speroff L "Oral contraceptives and venous thromboembolism." Int J Gynaecol Obstet 54 (1996): 45-50
  39. Poulter NR, Chang CL, Farley TMM, Meirik O, Marmot MG, Debertribeiro M, Medina E, Artigas J, Shen H, Zhong YH, Zhang DW, "Ischaemic stroke and combined oral contraceptives: results of an international, multicentre, case-control study." Lancet 348 (1996): 498-505
  40. Poulter NR, Chang CL, Farley TMM, Meirik O, Marmot MG "Haemorrhagic stroke, overall stroke risk, and combined oral contraceptives: results of an international, multicentre, case-control study." Lancet 348 (1996): 505-10
  41. Piegsa K, Guillebaud J "Oral contraceptives and the risk of DVT." Practitioner 240 (1996): 544
  42. Martinelli I, Rosendaal FR, Vandenbroucke JP, Mannucci PM "Oral contraceptives are a risk factor for cerebral vein thrombosis." Thromb Haemost 76 (1996): 477-8
  43. Farley TMM, Meirik O, Poulter NR, Chang CL, Marmot MG "Oral contraceptives and thrombotic diseases: impact of new epidemiological studies." Contraception 54 (1996): 193-5
  44. "Product Information. Ortho-Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho McNeil Pharmaceutical
  45. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho McNeil Pharmaceutical (2001):
  46. "Product Information. Demulen 1/50 (ethinyl estradiol-ethynodiol)." Searle
  47. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  48. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho McNeil Pharmaceutical (2001):
  49. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories (2001):
  50. "Product Information. Ortho-Novum 1/50 (mestranol-norethindrone)." Ortho McNeil Pharmaceutical
  51. Sidney S, Petitti DB, Quesenberry CP "Myocardial infarction and the use of estrogen and estrogen-progestogen in postmenopausal women." Ann Intern Med 127 (1997): 501-8
  52. Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs B, Vittinghoff E "Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women." JAMA 280 (1998): 605-13
  53. "Product Information. Ortho-Est (estropipate)." Ortho McNeil Pharmaceutical (2001):
  54. Petitti DB "Hormone replacement therapy and heart disease prevention: experimentation trumps observation." JAMA 280 (1998): 650-2
  55. Thorogood M "Risk of stroke in users of oral contraceptives." JAMA 281 (1999): 1255-6
  56. Mendelsohn ME, Karas RH "The protective effects of estrogen on the cardiovascular system." N Engl J Med 340 (1999): 1801-11
  57. "Product Information. Ortho Dienestrol (dienestrol topical)." Ortho McNeil Pharmaceutical
  58. "Product Information. Ogen (estropipate topical)." Pharmacia and Upjohn (2001):
  59. "Product Information. Estinyl (ethinyl estradiol)." Schering Corporation
  60. "Product Information. Estratab (esterified estrogens)." Solvay Pharmaceuticals Inc (2001):
  61. "Product Information. Nextstellis (drospirenone-estetrol)." Mayne Pharma (2021):

• Uterine Hemorrhage

  Major

  The use of estrogens is contraindicated in patients with undiagnosed, abnormal vaginal bleeding. Prolonged (> 1 year), unopposed estrogen use (i.e. estrogen without concomitant progestin therapy) has been associated with a significant, dose-related risk of endometrial carcinoma. The risk may be offset substantially by the addition of a progestin but may not be completely abolished. Prior to initiating estrogen therapy, appropriate diagnostic tests should be performed in patients with abnormal vaginal bleeding to rule out endometrial malignancy. The same applies if recurrent or persistent bleeding develops during estrogen therapy.

  29 sources

  1. Obrink A, Bunne G, Collen J, Tjernberg B "Endometrial cancer and exogenous estrogens." Acta Obstet Gynecol Scand 58 (1979): 123
  2. Spengler RF, Clarke EA, Woolever CA, Newman AM, Osborn RW "Exogenous estrogens and endometrial cancer: a case-control study and assessment of potential biases." Am J Epidemiol 114 (1981): 497-506
  3. Buring JE, Bain CJ, Ehrmann RL "Conjugated estrogen use and risk of endometrial cancer." Am J Epidemiol 124 (1986): 434-41
  4. Persson I, Adami HO, Bergkvist L, Lindgren A, Pettersson B, Hoover R, Schairer C "Risk of endometrial cancer after treatment with oestrogens alone or in conjunction with progestogens: results of a prospective study." BMJ 298 (1989): 147-51
  5. Antunes CM, Strolley PD, Rosenshein NB, Davies JL, Tonascia JA, Brown C, Burnett L, Rutledge A, Pokempner M, Garcia R "Endometrial cancer and estrogen use. Report of a large case-control study." N Engl J Med 300 (1979): 9-13
  6. Gordon J, Reagan JW, Finkle WD, Ziel HK "Estrogen and endometrial carcinoma. An independent pathology review supporting original risk estimate." N Engl J Med 297 (1977): 570-1
  7. Shapiro S, Kelly JP, Rosenberg L, Kaufman DW, Helmrich SP, Rosenshein NB, Lewis JL Jr, Knapp RC, Stolley PD, Schottenfeld D "Risk of localized and widespread endometrial cancer in relation to recent and discontinued use of conjugated estrogens." N Engl J Med 313 (1985): 969-72
  8. Gray LA Sr, Christopherson WM, Hoover RN "Estrogens and endometrial carcinoma." Obstet Gynecol 49 (1977): 385-9

  Show all 29 sourcesShow fewer sources

  9. Woodruff JD, Pickar JH "Incidence of endometrial hyperplasia in postmenopausal women taking conjugated estrogens (Premarin) with medroxyprogesterone acetate or conjugated estrogens alone." Am J Obstet Gynecol 170 (1994): 1213-23
  10. "Product Information. Premarin (conjugated estrogens)." Wyeth-Ayerst Laboratories (2001):
  11. "Product Information. Climara (estradiol)." Berlex Laboratories (2001):
  12. "Product Information. Estrace (estradiol)." Warner Chilcott Laboratories (2001):
  13. "Product Information. Estraderm (estradiol)." Ciba-Geigy Pharmaceuticals (2001):
  14. "Product Information. Vivelle (estradiol)." Ciba-Geigy Pharmaceuticals (2001):
  15. The Writing Group for the PEPI Trial "Effects of hormone replacement therapy on endometrial histology in postmenopausal women." JAMA 275 (1996): 370-5
  16. "Product Information. Ortho-Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho McNeil Pharmaceutical
  17. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho McNeil Pharmaceutical (2001):
  18. "Product Information. Demulen 1/50 (ethinyl estradiol-ethynodiol)." Searle
  19. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  20. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho McNeil Pharmaceutical (2001):
  21. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories (2001):
  22. "Product Information. Ortho-Novum 1/50 (mestranol-norethindrone)." Ortho McNeil Pharmaceutical
  23. "Product Information. Emcyt (estramustine)." Pharmacia and Upjohn (2001):
  24. "Product Information. Ortho-Est (estropipate)." Ortho McNeil Pharmaceutical (2001):
  25. "Product Information. Ortho Dienestrol (dienestrol topical)." Ortho McNeil Pharmaceutical
  26. "Product Information. Ogen (estropipate topical)." Pharmacia and Upjohn (2001):
  27. "Product Information. Estinyl (ethinyl estradiol)." Schering Corporation
  28. "Product Information. Estratab (esterified estrogens)." Solvay Pharmaceuticals Inc (2001):
  29. "Product Information. Nextstellis (drospirenone-estetrol)." Mayne Pharma (2021):

• Angioedema

  Moderate

  The use of exogenous estrogens may induce or exacerbate symptoms of angioedema, particularly in women with hereditary angioedema. Close monitoring is recommended when prescribing these agents to patients predisposed to angioedema.

  7 sources

  1. "Product Information. Ortho-Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho McNeil Pharmaceutical
  2. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho McNeil Pharmaceutical (2001):
  3. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho McNeil Pharmaceutical (2001):
  4. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories (2001):
  5. "Product Information. Ortho-Novum 1/50 (mestranol-norethindrone)." Ortho McNeil Pharmaceutical
  6. "Product Information. Ortho Dienestrol (dienestrol topical)." Ortho McNeil Pharmaceutical
  7. "Product Information. Nextstellis (drospirenone-estetrol)." Mayne Pharma (2021):

• Depressive Disorder

  Moderate

  The use of oral contraceptives has been associated with an increased incidence of depression. It is uncertain whether this effect is related to the estrogenic or the progestogenic component of the contraceptive, although excess progesterone activity is associated with depression. Patients with a history of depression receiving estrogen and/or progestogen therapy should be followed closely. The manufacturer of medroxyprogesterone recommends monitoring patients who have a history of depression and to not re- administer medroxyprogesterone if depression recurs.

  24 sources

  1. "Product Information. Depo-Provera (medroxyprogesterone)." Pharmacia and Upjohn (2001):
  2. "Product Information. Provera (medroxyprogesterone)." Pharmacia and Upjohn (2001):
  3. "Product Information. Premarin (conjugated estrogens)." Wyeth-Ayerst Laboratories (2001):
  4. "Product Information. Climara (estradiol)." Berlex Laboratories (2001):
  5. "Product Information. Estrace (estradiol)." Warner Chilcott Laboratories (2001):
  6. "Product Information. Estraderm (estradiol)." Ciba-Geigy Pharmaceuticals (2001):
  7. "Product Information. Vivelle (estradiol)." Ciba-Geigy Pharmaceuticals (2001):
  8. "Product Information. Ortho-Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho McNeil Pharmaceutical

  Show all 24 sourcesShow fewer sources

  9. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho McNeil Pharmaceutical (2001):
  10. "Product Information. Demulen 1/50 (ethinyl estradiol-ethynodiol)." Searle
  11. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  12. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho McNeil Pharmaceutical (2001):
  13. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories (2001):
  14. "Product Information. Ortho-Novum 1/50 (mestranol-norethindrone)." Ortho McNeil Pharmaceutical
  15. "Product Information. Ortho-Est (estropipate)." Ortho McNeil Pharmaceutical (2001):
  16. "Product Information. Ortho Dienestrol (dienestrol topical)." Ortho McNeil Pharmaceutical
  17. "Product Information. Ogen (estropipate topical)." Pharmacia and Upjohn (2001):
  18. "Product Information. Estinyl (ethinyl estradiol)." Schering Corporation
  19. "Product Information. Estratab (esterified estrogens)." Solvay Pharmaceuticals Inc (2001):
  20. "Product Information. Norplant System (levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  21. "Product Information. Micronor (norethindrone)." Ortho McNeil Pharmaceutical (2001):
  22. "Product Information. Ovrette (norgestrel)." Wyeth-Ayerst Laboratories (2001):
  23. "Product Information. Implanon (etonogestrel)." Organon Pharmaceuticals (2006):
  24. "Product Information. Nextstellis (drospirenone-estetrol)." Mayne Pharma (2021):

• Depressive Disorder

  Moderate

  The use of oral contraceptives has been associated with an increased incidence of depression. It is uncertain whether this effect is related to the estrogenic or the progestogenic component of the contraceptive, although excess progesterone activity is associated with depression. Patients with a history of depression receiving estrogen and/or progestogen therapy should be followed closely. The manufacturer of medroxyprogesterone recommends monitoring patients who have a history of depression and to not re- administer medroxyprogesterone if depression recurs.

  24 sources

  1. "Product Information. Depo-Provera (medroxyprogesterone)." Pharmacia and Upjohn (2001):
  2. "Product Information. Provera (medroxyprogesterone)." Pharmacia and Upjohn (2001):
  3. "Product Information. Premarin (conjugated estrogens)." Wyeth-Ayerst Laboratories (2001):
  4. "Product Information. Climara (estradiol)." Berlex Laboratories (2001):
  5. "Product Information. Estrace (estradiol)." Warner Chilcott Laboratories (2001):
  6. "Product Information. Estraderm (estradiol)." Ciba-Geigy Pharmaceuticals (2001):
  7. "Product Information. Vivelle (estradiol)." Ciba-Geigy Pharmaceuticals (2001):
  8. "Product Information. Ortho-Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho McNeil Pharmaceutical

  Show all 24 sourcesShow fewer sources

  9. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho McNeil Pharmaceutical (2001):
  10. "Product Information. Demulen 1/50 (ethinyl estradiol-ethynodiol)." Searle
  11. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  12. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho McNeil Pharmaceutical (2001):
  13. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories (2001):
  14. "Product Information. Ortho-Novum 1/50 (mestranol-norethindrone)." Ortho McNeil Pharmaceutical
  15. "Product Information. Ortho-Est (estropipate)." Ortho McNeil Pharmaceutical (2001):
  16. "Product Information. Ortho Dienestrol (dienestrol topical)." Ortho McNeil Pharmaceutical
  17. "Product Information. Ogen (estropipate topical)." Pharmacia and Upjohn (2001):
  18. "Product Information. Estinyl (ethinyl estradiol)." Schering Corporation
  19. "Product Information. Estratab (esterified estrogens)." Solvay Pharmaceuticals Inc (2001):
  20. "Product Information. Norplant System (levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  21. "Product Information. Micronor (norethindrone)." Ortho McNeil Pharmaceutical (2001):
  22. "Product Information. Ovrette (norgestrel)." Wyeth-Ayerst Laboratories (2001):
  23. "Product Information. Implanon (etonogestrel)." Organon Pharmaceuticals (2006):
  24. "Product Information. Nextstellis (drospirenone-estetrol)." Mayne Pharma (2021):

• Eye Diseases

  Moderate

  Estrogens and progestogens may cause retinal thrombosis. Oral contraceptives should be discontinued if there is unexplained partial or complete loss of vision; onset of proptosis or diplopia; papilledema; or retinal vascular lesions. Therapy with these agents should be administered cautiously in patients who have preexisting ocular problems and appropriate diagnostic and therapeutic measures should be instituted. Contact lens wearers who develop visual changes or changes in lens tolerance should be assessed by an ophthalmologist.

  13 sources

  1. "Product Information. Ortho-Novum 1/35 (ethinyl estradiol-norethindrone)." Ortho McNeil Pharmaceutical
  2. "Product Information. Ortho-Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho McNeil Pharmaceutical
  3. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho McNeil Pharmaceutical (2001):
  4. "Product Information. Demulen 1/50 (ethinyl estradiol-ethynodiol)." Searle
  5. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  6. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho McNeil Pharmaceutical (2001):
  7. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories (2001):
  8. "Product Information. Ortho-Novum 1/50 (mestranol-norethindrone)." Ortho McNeil Pharmaceutical

  Show all 13 sourcesShow fewer sources

  9. "Product Information. Norplant System (levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  10. "Product Information. Micronor (norethindrone)." Ortho McNeil Pharmaceutical (2001):
  11. "Product Information. Ovrette (norgestrel)." Wyeth-Ayerst Laboratories (2001):
  12. "Product Information. Prometrium (progesterone)." Virtus Pharmaceuticals LLC (2001):
  13. "Product Information. Nextstellis (drospirenone-estetrol)." Mayne Pharma (2021):

• Eye Diseases

  Moderate

  Estrogens and progestogens may cause retinal thrombosis. Oral contraceptives should be discontinued if there is unexplained partial or complete loss of vision; onset of proptosis or diplopia; papilledema; or retinal vascular lesions. Therapy with these agents should be administered cautiously in patients who have preexisting ocular problems and appropriate diagnostic and therapeutic measures should be instituted. Contact lens wearers who develop visual changes or changes in lens tolerance should be assessed by an ophthalmologist.

  13 sources

  1. "Product Information. Ortho-Novum 1/35 (ethinyl estradiol-norethindrone)." Ortho McNeil Pharmaceutical
  2. "Product Information. Ortho-Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho McNeil Pharmaceutical
  3. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho McNeil Pharmaceutical (2001):
  4. "Product Information. Demulen 1/50 (ethinyl estradiol-ethynodiol)." Searle
  5. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  6. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho McNeil Pharmaceutical (2001):
  7. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories (2001):
  8. "Product Information. Ortho-Novum 1/50 (mestranol-norethindrone)." Ortho McNeil Pharmaceutical

  Show all 13 sourcesShow fewer sources

  9. "Product Information. Norplant System (levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  10. "Product Information. Micronor (norethindrone)." Ortho McNeil Pharmaceutical (2001):
  11. "Product Information. Ovrette (norgestrel)." Wyeth-Ayerst Laboratories (2001):
  12. "Product Information. Prometrium (progesterone)." Virtus Pharmaceuticals LLC (2001):
  13. "Product Information. Nextstellis (drospirenone-estetrol)." Mayne Pharma (2021):

• Gallbladder Diseases

  Moderate

  A two- to four-fold increase in risk of gallbladder disease has been noted in women receiving postmenopausal estrogen therapy. The risk for gallbladder disease may be less for premenopausal women using oral contraceptives containing low-dose estrogens and/or progestins. Therapy with estrogens should be administered cautiously in patients with preexisting gallbladder disease.

  19 sources

  1. Boston Collaborative Drug Surveilance Program "Surgically confirmed gallbladder disease, venous thromboembolism, and breast tumors in relation to postmenopausal estrogen therapy." N Engl J Med 290 (1974): 15-9
  2. "Product Information. Premarin (conjugated estrogens)." Wyeth-Ayerst Laboratories (2001):
  3. "Product Information. Climara (estradiol)." Berlex Laboratories (2001):
  4. "Product Information. Estrace (estradiol)." Warner Chilcott Laboratories (2001):
  5. "Product Information. Estraderm (estradiol)." Ciba-Geigy Pharmaceuticals (2001):
  6. "Product Information. Vivelle (estradiol)." Ciba-Geigy Pharmaceuticals (2001):
  7. "Product Information. Ortho-Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho McNeil Pharmaceutical
  8. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho McNeil Pharmaceutical (2001):

  Show all 19 sourcesShow fewer sources

  9. "Product Information. Demulen 1/50 (ethinyl estradiol-ethynodiol)." Searle
  10. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  11. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho McNeil Pharmaceutical (2001):
  12. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories (2001):
  13. "Product Information. Ortho-Novum 1/50 (mestranol-norethindrone)." Ortho McNeil Pharmaceutical
  14. "Product Information. Ortho-Est (estropipate)." Ortho McNeil Pharmaceutical (2001):
  15. "Product Information. Ortho Dienestrol (dienestrol topical)." Ortho McNeil Pharmaceutical
  16. "Product Information. Ogen (estropipate topical)." Pharmacia and Upjohn (2001):
  17. "Product Information. Estinyl (ethinyl estradiol)." Schering Corporation
  18. "Product Information. Estratab (esterified estrogens)." Solvay Pharmaceuticals Inc (2001):
  19. "Product Information. Nextstellis (drospirenone-estetrol)." Mayne Pharma (2021):

• Glucose Intolerance

  Moderate

  Impaired glucose tolerance has been observed in some patients administered oral contraceptives and appears to be related primarily to the estrogen dose. However, progestogens can increase insulin secretion and produce insulin resistance to varying degrees, depending on the agent. Patients with diabetes mellitus should be monitored more closely during therapy with estrogens and/or progestogens, and adjustments made accordingly in their antidiabetic regimen.

  24 sources

  1. Haiba NA, el-Habashy MA, Said SA, Darwish EA, Abdel-Sayed WS, Nayel SE "Clinical evaluation of two monthly injectable contraceptives and their effects on some metabolic parameters." Contraception 39 (1989): 619-32
  2. Virutamasen P, Wongsrichanalai C, Tangkeo P, Nitichai Y, Rienprayoon D "Metabolic effects of depot-medroxyprogesterone acetate in long-term users: a cross-sectional study." Int J Gynaecol Obstet 24 (1986): 291-6
  3. Who Task Force on Long-acting Agents for Fertility Regulation "Metabolic side-effects of injectable depot-medroxyprogesterone acetate, 150 mg three-monthly, in undernourished lactating women." Bull World Health Organ 64 (1986): 587-94
  4. Garg SK, Chase HP, Marshall G, Hoops SL, Holmes DL, Jackson WE "Oral contraceptives and renal and retinal complications in young women with insulin-dependent diabetes mellitus." JAMA 271 (1994): 1099-102
  5. Hannaford PC, Kay CR "Oral contraceptives and diabetes mellitus." BMJ 299 (1989): 1315-6
  6. Stubblefield PG "Choosing the best oral contraceptive." Clin Obstet Gynecol 32 (1989): 316-28
  7. Spellacy WN, Ellingson AB, Tsibris JC "The effects of two triphasic oral contraceptives on carbohydrate metabolism in women during 1 year of use." Fertil Steril 51 (1989): 71-4
  8. Steinberg WM "Oral contraception: risks and benefits." Adv Contracept 5 (1989): 219-28

  Show all 24 sourcesShow fewer sources

  9. Derman R "Oral contraceptives: a reassessment." Obstet Gynecol Surv 44 (1989): 662-8
  10. Luciano AA, De Souza MJ, Roy MP, Schoenfeld MJ, Nulsen JC, Halvorson CV "Evaluation of low-dose estrogen and progestin therapy in postmenopausal women." J Reprod Med 38 (1993): 207-14
  11. Kaunitz AM "Long-acting injectable contraception with depot medroxyprogesterone acetate." Am J Obstet Gynecol 170 (1994): 1543-9
  12. Belchetz PE "Hormonal treatment of postmenopausal women." N Engl J Med 330 (1994): 1062-71
  13. "Product Information. Ortho-Novum 1/35 (ethinyl estradiol-norethindrone)." Ortho McNeil Pharmaceutical
  14. "Product Information. Ortho-Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho McNeil Pharmaceutical
  15. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho McNeil Pharmaceutical (2001):
  16. "Product Information. Demulen 1/50 (ethinyl estradiol-ethynodiol)." Searle
  17. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  18. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho McNeil Pharmaceutical (2001):
  19. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories (2001):
  20. "Product Information. Ortho-Novum 1/50 (mestranol-norethindrone)." Ortho McNeil Pharmaceutical
  21. "Product Information. Norplant System (levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  22. "Product Information. Micronor (norethindrone)." Ortho McNeil Pharmaceutical (2001):
  23. "Product Information. Ovrette (norgestrel)." Wyeth-Ayerst Laboratories (2001):
  24. "Product Information. Nextstellis (drospirenone-estetrol)." Mayne Pharma (2021):

• Glucose Intolerance

  Moderate

  Impaired glucose tolerance has been observed in some patients administered oral contraceptives and appears to be related primarily to the estrogen dose. However, progestogens can increase insulin secretion and produce insulin resistance to varying degrees, depending on the agent. Patients with diabetes mellitus should be monitored more closely during therapy with estrogens and/or progestogens, and adjustments made accordingly in their antidiabetic regimen.

  24 sources

  1. Haiba NA, el-Habashy MA, Said SA, Darwish EA, Abdel-Sayed WS, Nayel SE "Clinical evaluation of two monthly injectable contraceptives and their effects on some metabolic parameters." Contraception 39 (1989): 619-32
  2. Virutamasen P, Wongsrichanalai C, Tangkeo P, Nitichai Y, Rienprayoon D "Metabolic effects of depot-medroxyprogesterone acetate in long-term users: a cross-sectional study." Int J Gynaecol Obstet 24 (1986): 291-6
  3. Who Task Force on Long-acting Agents for Fertility Regulation "Metabolic side-effects of injectable depot-medroxyprogesterone acetate, 150 mg three-monthly, in undernourished lactating women." Bull World Health Organ 64 (1986): 587-94
  4. Garg SK, Chase HP, Marshall G, Hoops SL, Holmes DL, Jackson WE "Oral contraceptives and renal and retinal complications in young women with insulin-dependent diabetes mellitus." JAMA 271 (1994): 1099-102
  5. Hannaford PC, Kay CR "Oral contraceptives and diabetes mellitus." BMJ 299 (1989): 1315-6
  6. Stubblefield PG "Choosing the best oral contraceptive." Clin Obstet Gynecol 32 (1989): 316-28
  7. Spellacy WN, Ellingson AB, Tsibris JC "The effects of two triphasic oral contraceptives on carbohydrate metabolism in women during 1 year of use." Fertil Steril 51 (1989): 71-4
  8. Steinberg WM "Oral contraception: risks and benefits." Adv Contracept 5 (1989): 219-28

  Show all 24 sourcesShow fewer sources

  9. Derman R "Oral contraceptives: a reassessment." Obstet Gynecol Surv 44 (1989): 662-8
  10. Luciano AA, De Souza MJ, Roy MP, Schoenfeld MJ, Nulsen JC, Halvorson CV "Evaluation of low-dose estrogen and progestin therapy in postmenopausal women." J Reprod Med 38 (1993): 207-14
  11. Kaunitz AM "Long-acting injectable contraception with depot medroxyprogesterone acetate." Am J Obstet Gynecol 170 (1994): 1543-9
  12. Belchetz PE "Hormonal treatment of postmenopausal women." N Engl J Med 330 (1994): 1062-71
  13. "Product Information. Ortho-Novum 1/35 (ethinyl estradiol-norethindrone)." Ortho McNeil Pharmaceutical
  14. "Product Information. Ortho-Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho McNeil Pharmaceutical
  15. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho McNeil Pharmaceutical (2001):
  16. "Product Information. Demulen 1/50 (ethinyl estradiol-ethynodiol)." Searle
  17. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  18. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho McNeil Pharmaceutical (2001):
  19. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories (2001):
  20. "Product Information. Ortho-Novum 1/50 (mestranol-norethindrone)." Ortho McNeil Pharmaceutical
  21. "Product Information. Norplant System (levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  22. "Product Information. Micronor (norethindrone)." Ortho McNeil Pharmaceutical (2001):
  23. "Product Information. Ovrette (norgestrel)." Wyeth-Ayerst Laboratories (2001):
  24. "Product Information. Nextstellis (drospirenone-estetrol)." Mayne Pharma (2021):

• Hypercalcemia

  Moderate

  Estrogens influence the metabolism of calcium and phosphorus. Intestinal absorption and retention of calcium are increased, which may occasionally result in hypercalcemia. Therapy with estrogens should be administered cautiously in patients with preexisting hypercalcemia, renal dysfunction, or metabolic bone diseases that are associated with hypercalcemia.

  7 sources

  1. "Product Information. Premarin (conjugated estrogens)." Wyeth-Ayerst Laboratories (2001):
  2. "Product Information. Climara (estradiol)." Berlex Laboratories (2001):
  3. "Product Information. Estrace (estradiol)." Warner Chilcott Laboratories (2001):
  4. "Product Information. Estraderm (estradiol)." Ciba-Geigy Pharmaceuticals (2001):
  5. "Product Information. Vivelle (estradiol)." Ciba-Geigy Pharmaceuticals (2001):
  6. "Product Information. Emcyt (estramustine)." Pharmacia and Upjohn (2001):
  7. "Product Information. Duavee (bazedoxifene-conjugated estrogens)." Pfizer U.S. Pharmaceuticals Group (2013):

• Hyperlipidemias

  Moderate

  Some progestogenic agents may elevate plasma LDL levels and/or lower HDL levels, although data have been inconsistent. Patients with preexisting hyperlipidemia may require closer monitoring during progestogen therapy, and adjustments made accordingly in their lipid-lowering regimen.

  17 sources

  1. Barnes RB, Roy S, Lobo RA "Comparison of lipid and androgen levels after conjugated estrogen or depo-medroxyprogesterone acetate treatment in postmenopausal women." Obstet Gynecol 66 (1985): 216-9
  2. Haiba NA, el-Habashy MA, Said SA, Darwish EA, Abdel-Sayed WS, Nayel SE "Clinical evaluation of two monthly injectable contraceptives and their effects on some metabolic parameters." Contraception 39 (1989): 619-32
  3. Virutamasen P, Wongsrichanalai C, Tangkeo P, Nitichai Y, Rienprayoon D "Metabolic effects of depot-medroxyprogesterone acetate in long-term users: a cross-sectional study." Int J Gynaecol Obstet 24 (1986): 291-6
  4. Teichmann AT, Wander HE, Cremer P, et al. "Medroxyprogesterone acetate and lipid metabolic changes." Arzneimittelforschung 37 (1987): 573-77
  5. Who Task Force on Long-acting Agents for Fertility Regulation "Metabolic side-effects of injectable depot-medroxyprogesterone acetate, 150 mg three-monthly, in undernourished lactating women." Bull World Health Organ 64 (1986): 587-94
  6. Luciano AA, De Souza MJ, Roy MP, Schoenfeld MJ, Nulsen JC, Halvorson CV "Evaluation of low-dose estrogen and progestin therapy in postmenopausal women." J Reprod Med 38 (1993): 207-14
  7. "Product Information. Depo-Provera (medroxyprogesterone)." Pharmacia and Upjohn (2001):
  8. "Product Information. Provera (medroxyprogesterone)." Pharmacia and Upjohn (2001):

  Show all 17 sourcesShow fewer sources

  9. "Product Information. Ortho-Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho McNeil Pharmaceutical
  10. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho McNeil Pharmaceutical (2001):
  11. "Product Information. Demulen 1/50 (ethinyl estradiol-ethynodiol)." Searle
  12. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  13. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho McNeil Pharmaceutical (2001):
  14. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories (2001):
  15. "Product Information. Norplant System (levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  16. "Product Information. Micronor (norethindrone)." Ortho McNeil Pharmaceutical (2001):
  17. "Product Information. Ovrette (norgestrel)." Wyeth-Ayerst Laboratories (2001):

• Hyperlipidemias

  Moderate

  Although estrogens have generally favorable effects on plasma lipids, including increases in HDL and decreases in total cholesterol and LDL, they have also been associated with significant elevations in triglyceride levels, particularly when high dosages are used. Severe hyperlipidemia is known to sometimes cause pancreatitis. Patients with preexisting hyperlipidemia may require closer monitoring during estrogen therapy, and adjustments made accordingly in their lipid-lowering regimen.

  25 sources

  1. Molitch ME, Oill P, Odell WD "Massive hyperlipemia during estrogen therapy." JAMA 227 (1974): 522-5
  2. Janaud A, Rouffy J, Upmalis D, Dain MP "A comparison study of lipid and androgen metabolism with triphasic oral contraceptive formulations containing norgestimate or levonorgestrel." Acta Obstet Gynecol Scand Suppl 156 (1992): 33-8
  3. Steinberg WM "Oral contraception: risks and benefits." Adv Contracept 5 (1989): 219-28
  4. Burkman RT, Zacur HA, Kimball AW, Kwiterovich P, Bell WR "Oral contraceptives and lipids and lipoproteins: Part I--Variations in mean levels by oral contraceptive type." Contraception 40 (1989): 553-61
  5. Derman R "Oral contraceptives: a reassessment." Obstet Gynecol Surv 44 (1989): 662-8
  6. Godsland IF, Crook D "Update on the metabolic effects of steroidal contraceptives and their relationship to cardiovascular disease risk." Am J Obstet Gynecol 170 (1994): 1528-36
  7. "Product Information. Premarin (conjugated estrogens)." Wyeth-Ayerst Laboratories (2001):
  8. "Product Information. Climara (estradiol)." Berlex Laboratories (2001):

  Show all 25 sourcesShow fewer sources

  9. "Product Information. Estrace (estradiol)." Warner Chilcott Laboratories (2001):
  10. "Product Information. Estraderm (estradiol)." Ciba-Geigy Pharmaceuticals (2001):
  11. "Product Information. Vivelle (estradiol)." Ciba-Geigy Pharmaceuticals (2001):
  12. "Product Information. Ortho-Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho McNeil Pharmaceutical
  13. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho McNeil Pharmaceutical (2001):
  14. "Product Information. Demulen 1/50 (ethinyl estradiol-ethynodiol)." Searle
  15. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  16. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho McNeil Pharmaceutical (2001):
  17. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories (2001):
  18. "Product Information. Ortho-Novum 1/50 (mestranol-norethindrone)." Ortho McNeil Pharmaceutical
  19. Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs B, Vittinghoff E "Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women." JAMA 280 (1998): 605-13
  20. "Product Information. Ortho-Est (estropipate)." Ortho McNeil Pharmaceutical (2001):
  21. "Product Information. Ortho Dienestrol (dienestrol topical)." Ortho McNeil Pharmaceutical
  22. "Product Information. Ogen (estropipate topical)." Pharmacia and Upjohn (2001):
  23. "Product Information. Estinyl (ethinyl estradiol)." Schering Corporation
  24. "Product Information. Estratab (esterified estrogens)." Solvay Pharmaceuticals Inc (2001):
  25. "Product Information. Nextstellis (drospirenone-estetrol)." Mayne Pharma (2021):

• Liver Diseases

  Moderate

  Estrogens are primarily metabolized by the liver. Patients with impaired hepatic function may be at increased risk for adverse effects associated with estrogen administration due to decreased drug clearance. Therapy with estrogens should be administered cautiously in patients with liver disease. In addition, clinicians should be aware that estrogen therapy may affect liver function tests. Increased sulfobromophthalein retention has been reported with the use of estrogen-containing oral contraceptives and may be expected with larger doses of estrogens.

  23 sources

  1. Bhavnani BR, Cecutti A "Pharmacokinetics of 17 beta-dihydroequilin sulfate and 17 beta- dihydroequilin in normal postmenopausal women." J Clin Endocrinol Metab 78 (1994): 197-204
  2. Adlercrueuta H "Hepatic metabolism of estrogens in health and disease." N Engl J Med 290 (1974): 1081-3
  3. Goldzieher JW "Pharmacology of contraceptive steroids: a brief review." Am J Obstet Gynecol 160 (1989): 1260-4
  4. Kuhnz W, al-Yacoub G, Fuhrmeister A "Pharmacokinetics of levonorgestrel and ethinylestradiol in 9 women who received a low-dose oral contraceptive over a treatment period of 3 months and the same contraceptive formulation." Contraception 46 (1992): 455-69
  5. "Product Information. Premarin (conjugated estrogens)." Wyeth-Ayerst Laboratories (2001):
  6. "Product Information. Climara (estradiol)." Berlex Laboratories (2001):
  7. "Product Information. Estrace (estradiol)." Warner Chilcott Laboratories (2001):
  8. "Product Information. Estraderm (estradiol)." Ciba-Geigy Pharmaceuticals (2001):

  Show all 23 sourcesShow fewer sources

  9. "Product Information. Vivelle (estradiol)." Ciba-Geigy Pharmaceuticals (2001):
  10. "Product Information. Ortho-Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho McNeil Pharmaceutical
  11. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho McNeil Pharmaceutical (2001):
  12. "Product Information. Demulen 1/50 (ethinyl estradiol-ethynodiol)." Searle
  13. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  14. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho McNeil Pharmaceutical (2001):
  15. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories (2001):
  16. "Product Information. Ortho-Novum 1/50 (mestranol-norethindrone)." Ortho McNeil Pharmaceutical
  17. "Product Information. Emcyt (estramustine)." Pharmacia and Upjohn (2001):
  18. "Product Information. Ortho-Est (estropipate)." Ortho McNeil Pharmaceutical (2001):
  19. "Product Information. Ortho Dienestrol (dienestrol topical)." Ortho McNeil Pharmaceutical
  20. "Product Information. Ogen (estropipate topical)." Pharmacia and Upjohn (2001):
  21. "Product Information. Estinyl (ethinyl estradiol)." Schering Corporation
  22. "Product Information. Estratab (esterified estrogens)." Solvay Pharmaceuticals Inc (2001):
  23. "Product Information. Nextstellis (drospirenone-estetrol)." Mayne Pharma (2021):

• Long QT Syndrome

  Moderate

  Androgen deprivation therapy may prolong the QT/QTc interval. Health care providers should consider if benefits of therapy outweigh the potential risks in patients with congenital long QT syndrome, congestive heart failure, electrolyte abnormalities, or taking other drugs that can also prolong the QT interval. Consider periodic monitoring of EKG and electrolytes.

  2 sources

  1. "Product Information. Firmagon (degarelix)." Ferring Pharmaceuticals Inc (2013):
  2. "Product Information. Orgovyx (relugolix)." Myovant Sciences, Inc. (2021):

• Melanosis

  Moderate

  The use of exogenous estrogens may occasionally cause chloasma, especially in women with a history of chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation while taking combination oral contraceptives.

  7 sources

  1. "Product Information. Ortho-Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho McNeil Pharmaceutical
  2. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho McNeil Pharmaceutical (2001):
  3. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho McNeil Pharmaceutical (2001):
  4. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories (2001):
  5. "Product Information. Ortho-Novum 1/50 (mestranol-norethindrone)." Ortho McNeil Pharmaceutical
  6. "Product Information. Ortho Dienestrol (dienestrol topical)." Ortho McNeil Pharmaceutical
  7. "Product Information. Nextstellis (drospirenone-estetrol)." Mayne Pharma (2021):

• Thyroid Diseases

  Moderate

  When administering estrogen and/or progestogen therapy in patients with thyroid disorders, clinicians should be aware that these hormones may affect thyroid function tests. Changes have mostly been reported with the use of combination oral contraceptives. Specifically, thyroid-binding globulin (TBG) may be increased, resulting in elevated circulating total thyroid hormone, as measured by PBI (protein-bound iodine), T4 by column or radioimmunoassay, or T3 by radioimmunoassay. Free T3 resin uptake may be decreased. On the contrary, a decrease in TBG and, consequently, thyroxine concentration, has been reported by the manufacturers of the progestin-only (norethindrone) oral contraceptives.

  25 sources

  1. "Product Information. Depo-Provera (medroxyprogesterone)." Pharmacia and Upjohn (2001):
  2. "Product Information. Provera (medroxyprogesterone)." Pharmacia and Upjohn (2001):
  3. "Product Information. Premarin (conjugated estrogens)." Wyeth-Ayerst Laboratories (2001):
  4. "Product Information. Deltasone (prednisone)." Pharmacia and Upjohn (2001):
  5. "Product Information. Climara (estradiol)." Berlex Laboratories (2001):
  6. "Product Information. Estrace (estradiol)." Warner Chilcott Laboratories (2001):
  7. "Product Information. Estraderm (estradiol)." Ciba-Geigy Pharmaceuticals (2001):
  8. "Product Information. Vivelle (estradiol)." Ciba-Geigy Pharmaceuticals (2001):

  Show all 25 sourcesShow fewer sources

  9. "Product Information. Ortho-Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho McNeil Pharmaceutical
  10. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho McNeil Pharmaceutical (2001):
  11. "Product Information. Demulen 1/50 (ethinyl estradiol-ethynodiol)." Searle
  12. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  13. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho McNeil Pharmaceutical (2001):
  14. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories (2001):
  15. "Product Information. Ortho-Novum 1/50 (mestranol-norethindrone)." Ortho McNeil Pharmaceutical
  16. "Product Information. Emcyt (estramustine)." Pharmacia and Upjohn (2001):
  17. "Product Information. Ortho-Est (estropipate)." Ortho McNeil Pharmaceutical (2001):
  18. "Product Information. Ortho Dienestrol (dienestrol topical)." Ortho McNeil Pharmaceutical
  19. "Product Information. Ogen (estropipate topical)." Pharmacia and Upjohn (2001):
  20. "Product Information. Estinyl (ethinyl estradiol)." Schering Corporation
  21. "Product Information. Estratab (esterified estrogens)." Solvay Pharmaceuticals Inc (2001):
  22. "Product Information. Norplant System (levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  23. "Product Information. Micronor (norethindrone)." Ortho McNeil Pharmaceutical (2001):
  24. "Product Information. Ovrette (norgestrel)." Wyeth-Ayerst Laboratories (2001):
  25. "Product Information. Nextstellis (drospirenone-estetrol)." Mayne Pharma (2021):

• Thyroid Diseases

  Moderate

  When administering estrogen and/or progestogen therapy in patients with thyroid disorders, clinicians should be aware that these hormones may affect thyroid function tests. Changes have mostly been reported with the use of combination oral contraceptives. Specifically, thyroid-binding globulin (TBG) may be increased, resulting in elevated circulating total thyroid hormone, as measured by PBI (protein-bound iodine), T4 by column or radioimmunoassay, or T3 by radioimmunoassay. Free T3 resin uptake may be decreased. On the contrary, a decrease in TBG and, consequently, thyroxine concentration, has been reported by the manufacturers of the progestin-only (norethindrone) oral contraceptives.

  25 sources

  1. "Product Information. Depo-Provera (medroxyprogesterone)." Pharmacia and Upjohn (2001):
  2. "Product Information. Provera (medroxyprogesterone)." Pharmacia and Upjohn (2001):
  3. "Product Information. Premarin (conjugated estrogens)." Wyeth-Ayerst Laboratories (2001):
  4. "Product Information. Deltasone (prednisone)." Pharmacia and Upjohn (2001):
  5. "Product Information. Climara (estradiol)." Berlex Laboratories (2001):
  6. "Product Information. Estrace (estradiol)." Warner Chilcott Laboratories (2001):
  7. "Product Information. Estraderm (estradiol)." Ciba-Geigy Pharmaceuticals (2001):
  8. "Product Information. Vivelle (estradiol)." Ciba-Geigy Pharmaceuticals (2001):

  Show all 25 sourcesShow fewer sources

  9. "Product Information. Ortho-Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho McNeil Pharmaceutical
  10. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho McNeil Pharmaceutical (2001):
  11. "Product Information. Demulen 1/50 (ethinyl estradiol-ethynodiol)." Searle
  12. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  13. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho McNeil Pharmaceutical (2001):
  14. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories (2001):
  15. "Product Information. Ortho-Novum 1/50 (mestranol-norethindrone)." Ortho McNeil Pharmaceutical
  16. "Product Information. Emcyt (estramustine)." Pharmacia and Upjohn (2001):
  17. "Product Information. Ortho-Est (estropipate)." Ortho McNeil Pharmaceutical (2001):
  18. "Product Information. Ortho Dienestrol (dienestrol topical)." Ortho McNeil Pharmaceutical
  19. "Product Information. Ogen (estropipate topical)." Pharmacia and Upjohn (2001):
  20. "Product Information. Estinyl (ethinyl estradiol)." Schering Corporation
  21. "Product Information. Estratab (esterified estrogens)." Solvay Pharmaceuticals Inc (2001):
  22. "Product Information. Norplant System (levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  23. "Product Information. Micronor (norethindrone)." Ortho McNeil Pharmaceutical (2001):
  24. "Product Information. Ovrette (norgestrel)." Wyeth-Ayerst Laboratories (2001):
  25. "Product Information. Nextstellis (drospirenone-estetrol)." Mayne Pharma (2021):

• Water-Electrolyte Imbalance

  Moderate

  Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.

  27 sources

  1. Leiman G "Depo-medroxyprogesterone acetate as a contraceptive agent: its effect on weight and blood pressure." Am J Obstet Gynecol 114 (1972): 97-102
  2. "Product Information. Depo-Provera (medroxyprogesterone)." Pharmacia and Upjohn (2001):
  3. "Product Information. Provera (medroxyprogesterone)." Pharmacia and Upjohn (2001):
  4. "Product Information. Premarin (conjugated estrogens)." Wyeth-Ayerst Laboratories (2001):
  5. "Product Information. Climara (estradiol)." Berlex Laboratories (2001):
  6. "Product Information. Estrace (estradiol)." Warner Chilcott Laboratories (2001):
  7. "Product Information. Estraderm (estradiol)." Ciba-Geigy Pharmaceuticals (2001):
  8. "Product Information. Vivelle (estradiol)." Ciba-Geigy Pharmaceuticals (2001):

  Show all 27 sourcesShow fewer sources

  9. "Product Information. Ortho-Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho McNeil Pharmaceutical
  10. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho McNeil Pharmaceutical (2001):
  11. "Product Information. Demulen 1/50 (ethinyl estradiol-ethynodiol)." Searle
  12. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  13. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho McNeil Pharmaceutical (2001):
  14. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories (2001):
  15. "Product Information. Ortho-Novum 1/50 (mestranol-norethindrone)." Ortho McNeil Pharmaceutical
  16. "Product Information. Emcyt (estramustine)." Pharmacia and Upjohn (2001):
  17. "Product Information. Megace (megestrol)." Bristol-Myers Squibb (2001):
  18. "Product Information. Ortho-Est (estropipate)." Ortho McNeil Pharmaceutical (2001):
  19. "Product Information. Ortho Dienestrol (dienestrol topical)." Ortho McNeil Pharmaceutical
  20. "Product Information. Ogen (estropipate topical)." Pharmacia and Upjohn (2001):
  21. "Product Information. Estinyl (ethinyl estradiol)." Schering Corporation
  22. "Product Information. Estratab (esterified estrogens)." Solvay Pharmaceuticals Inc (2001):
  23. "Product Information. Norplant System (levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  24. "Product Information. Micronor (norethindrone)." Ortho McNeil Pharmaceutical (2001):
  25. "Product Information. Ovrette (norgestrel)." Wyeth-Ayerst Laboratories (2001):
  26. "Product Information. Prometrium (progesterone)." Virtus Pharmaceuticals LLC (2001):
  27. "Product Information. Implanon (etonogestrel)." Organon Pharmaceuticals (2006):

• Water-Electrolyte Imbalance

  Moderate

  Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.

  27 sources

  1. Leiman G "Depo-medroxyprogesterone acetate as a contraceptive agent: its effect on weight and blood pressure." Am J Obstet Gynecol 114 (1972): 97-102
  2. "Product Information. Depo-Provera (medroxyprogesterone)." Pharmacia and Upjohn (2001):
  3. "Product Information. Provera (medroxyprogesterone)." Pharmacia and Upjohn (2001):
  4. "Product Information. Premarin (conjugated estrogens)." Wyeth-Ayerst Laboratories (2001):
  5. "Product Information. Climara (estradiol)." Berlex Laboratories (2001):
  6. "Product Information. Estrace (estradiol)." Warner Chilcott Laboratories (2001):
  7. "Product Information. Estraderm (estradiol)." Ciba-Geigy Pharmaceuticals (2001):
  8. "Product Information. Vivelle (estradiol)." Ciba-Geigy Pharmaceuticals (2001):

  Show all 27 sourcesShow fewer sources

  9. "Product Information. Ortho-Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho McNeil Pharmaceutical
  10. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho McNeil Pharmaceutical (2001):
  11. "Product Information. Demulen 1/50 (ethinyl estradiol-ethynodiol)." Searle
  12. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  13. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho McNeil Pharmaceutical (2001):
  14. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories (2001):
  15. "Product Information. Ortho-Novum 1/50 (mestranol-norethindrone)." Ortho McNeil Pharmaceutical
  16. "Product Information. Emcyt (estramustine)." Pharmacia and Upjohn (2001):
  17. "Product Information. Megace (megestrol)." Bristol-Myers Squibb (2001):
  18. "Product Information. Ortho-Est (estropipate)." Ortho McNeil Pharmaceutical (2001):
  19. "Product Information. Ortho Dienestrol (dienestrol topical)." Ortho McNeil Pharmaceutical
  20. "Product Information. Ogen (estropipate topical)." Pharmacia and Upjohn (2001):
  21. "Product Information. Estinyl (ethinyl estradiol)." Schering Corporation
  22. "Product Information. Estratab (esterified estrogens)." Solvay Pharmaceuticals Inc (2001):
  23. "Product Information. Norplant System (levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  24. "Product Information. Micronor (norethindrone)." Ortho McNeil Pharmaceutical (2001):
  25. "Product Information. Ovrette (norgestrel)." Wyeth-Ayerst Laboratories (2001):
  26. "Product Information. Prometrium (progesterone)." Virtus Pharmaceuticals LLC (2001):
  27. "Product Information. Implanon (etonogestrel)." Organon Pharmaceuticals (2006):

• Weight Gain

  Minor

  Progestogens can cause weight gain, which may be significant (as is the case with parenteral medroxyprogesterone) and undesirable in obese patients attempting to lose weight.

  13 sources

  1. Leiman G "Depo-medroxyprogesterone acetate as a contraceptive agent: its effect on weight and blood pressure." Am J Obstet Gynecol 114 (1972): 97-102
  2. Amatayakul K, Sivasomboon B, Thanangkul O "A study of the mechanism of weight gain in medroxyprogesterone acetate users." Contraception 22 (1980): 605-22
  3. "Product Information. Depo-Provera (medroxyprogesterone)." Pharmacia and Upjohn (2001):
  4. "Product Information. Provera (medroxyprogesterone)." Pharmacia and Upjohn (2001):
  5. "Product Information. Ortho-Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho McNeil Pharmaceutical
  6. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho McNeil Pharmaceutical (2001):
  7. "Product Information. Demulen 1/50 (ethinyl estradiol-ethynodiol)." Searle
  8. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories (2001):

  Show all 13 sourcesShow fewer sources

  9. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho McNeil Pharmaceutical (2001):
  10. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories (2001):
  11. "Product Information. Norplant System (levonorgestrel)." Wyeth-Ayerst Laboratories (2001):
  12. "Product Information. Micronor (norethindrone)." Ortho McNeil Pharmaceutical (2001):
  13. "Product Information. Ovrette (norgestrel)." Wyeth-Ayerst Laboratories (2001):

Therapeutic duplication

Drug classes that overlap with Relugolix + Estradiol + Norethindrone, so taking both doubles up the same effect. This source publishes no per-row citations for duplication.

• gonadotropin-releasing hormone a

  The recommended maximum number of medicines in the 'gonadotropin-releasing hormone antagonists' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'gonadotropin-releasing hormone antagonists' category.

  Example product in the source data (US market): Oriahnn