Norethisterone Acetate 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

Conditions

Conditions in which Norethisterone Acetate 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):

• 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):

• 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):

• 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):

• 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):

• 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):

• 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):

• 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):