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Ena (estradiol / norethindrone) Disease Interactions

There are 23 disease interactions with Ena (estradiol / norethindrone):

Major

Contraceptives (Includes Ena) ↔ Abnormal Genital Bleeding

Severe Potential Hazard, Moderate plausibility

Applies to: Abnormal Uterine Bleeding

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.

Major

Estrogens (Includes Ena) ↔ Abnormal Vaginal Bleeding

Severe Potential Hazard, High plausibility

Applies to: Abnormal Uterine Bleeding

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.

References

  1. Buring JE, Bain CJ, Ehrmann RL "Conjugated estrogen use and risk of endometrial cancer." Am J Epidemiol 124 (1986): 434-41
  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. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  4. "Product Information. Estrace (estradiol)." Warner Chilcott Laboratories, Rockaway, NJ.
  5. The Writing Group for the PEPI Trial "Effects of hormone replacement therapy on endometrial histology in postmenopausal women." JAMA 275 (1996): 370-5
  6. 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
  7. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  8. "Product Information. Climara (estradiol)." Berlex, Richmond, CA.
  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. Estratab (esterified estrogens)" Solvay Pharmaceuticals Inc, Marietta, GA.
  11. "Product Information. Estraderm (estradiol)." Ciba Pharmaceuticals, Summit, NJ.
  12. Obrink A, Bunne G, Collen J, Tjernberg B "Endometrial cancer and exogenous estrogens." Acta Obstet Gynecol Scand 58 (1979): 123
  13. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  14. "Product Information. Ortho Novum 1/50 (mestranol-norethindrone)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  15. "Product Information. Emcyt (estramustine)." Pharmacia and Upjohn, Kalamazoo, MI.
  16. Gray LA Sr, Christopherson WM, Hoover RN "Estrogens and endometrial carcinoma." Obstet Gynecol 49 (1977): 385-9
  17. "Product Information. Vivelle (estradiol)." Ciba Pharmaceuticals, Summit, NJ.
  18. "Product Information. Ogen (estropipate topical)" Pharmacia and Upjohn, Kalamazoo, MI.
  19. "Product Information. Ortho Dienestrol Cream (dienestrol topical)" Ortho McNeil Pharmaceutical, Raritan, NJ.
  20. "Product Information. Premarin (conjugated estrogens)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  21. "Product Information. Ortho-Est (estropipate)." Ortho McNeil Pharmaceutical, Raritan, NJ.
  22. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  23. "Product Information. Demulen (ethinyl estradiol-ethynodiol)." Searle, Skokie, IL.
  24. 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
  25. "Product Information. Estinyl Tablets (ethinyl estradiol)" Schering Corporation, Kenilworth, NJ.
  26. 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
  27. 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
  28. "Product Information. Ortho Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho Pharmaceutical Corporation, Raritan, NJ.
View all 28 references
Major

Estrogens (Includes Ena) ↔ Carcinomas (Estrogenic)

Severe Potential Hazard, High plausibility

Applies to: Neoplasia -- Estrogen Dependent

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.

References

  1. Schlesselman JJ "Oral contraceptives and breast cancer." Am J Obstet Gynecol 163 (1990): 1379-87
  2. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  3. "Product Information. Ortho-Est (estropipate)." Ortho McNeil Pharmaceutical, Raritan, NJ.
  4. "Product Information. Estinyl Tablets (ethinyl estradiol)" Schering Corporation, Kenilworth, NJ.
  5. 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
  6. Mishell DR "Contraception." N Engl J Med 320 (1989): 777-85
  7. Turnquest MA "Oral contraceptive use and incidence of cervical intraepithelial neoplasia." Am J Obstet Gynecol 168 (1993): 1895-6
  8. 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
  9. 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
  10. Buring JE, Bain CJ, Ehrmann RL "Conjugated estrogen use and risk of endometrial cancer." Am J Epidemiol 124 (1986): 434-41
  11. 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
  12. 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
  13. 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
  14. "Product Information. Estrace (estradiol)." Warner Chilcott Laboratories, Rockaway, NJ.
  15. "Product Information. Demulen (ethinyl estradiol-ethynodiol)." Searle, Skokie, IL.
  16. 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
  17. "Product Information. Estratab (esterified estrogens)" Solvay Pharmaceuticals Inc, Marietta, GA.
  18. "Product Information. Climara (estradiol)." Berlex, Richmond, CA.
  19. "Product Information. Ogen (estropipate topical)" Pharmacia and Upjohn, Kalamazoo, MI.
  20. 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
  21. 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
  22. 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
  23. 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
  24. 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
  25. Brinton LA "Oral contraceptives and cervical neoplasia." Contraception 43 (1991): 581-95
  26. Ewertz M "Oral contraceptives and breast cancer risk in Denmark." Eur J Cancer 28A (1992): 1176-81
  27. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  28. 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
  29. 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
  30. Thomas DB "Oral contraceptives and breast cancer: review of the epidemiologic literature." Contraception 43 (1991): 597-642
  31. Gray LA Sr, Christopherson WM, Hoover RN "Estrogens and endometrial carcinoma." Obstet Gynecol 49 (1977): 385-9
  32. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  33. "Product Information. Estraderm (estradiol)." Ciba Pharmaceuticals, Summit, NJ.
  34. Murray PP, Stadel BV, Schlesselman JJ "Oral contraceptive use in women with a family history of breast cancer." Obstet Gynecol 73 (1989): 977-83
  35. 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
  36. Kaunitz AM "Oral contraceptives and gynecologic cancer: an update for the 1990s." Am J Obstet Gynecol 167 (1992): 1171-6
  37. 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
  38. Obrink A, Bunne G, Collen J, Tjernberg B "Endometrial cancer and exogenous estrogens." Acta Obstet Gynecol Scand 58 (1979): 123
  39. "Product Information. Ortho Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  40. Lund E "Oral contraceptives and breast cancer. A review with some comments on mathematical models." Acta Oncol 31 (1992): 183-6
  41. 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
  42. "Product Information. Ortho Novum 1/50 (mestranol-norethindrone)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  43. 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
  44. The Writing Group for the PEPI Trial "Effects of hormone replacement therapy on endometrial histology in postmenopausal women." JAMA 275 (1996): 370-5
  45. 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
  46. 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
  47. 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
  48. "Oral contraceptives and neoplasia. WHO Scientific Group." World Health Organ Tech Rep Ser 817 (1992): 1-46
  49. 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
  50. 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
  51. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  52. Rettig BA, Lemon HM "Cancers related to contraceptive use." Br J Cancer 74 (1996): 1509-10
  53. 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
  54. 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
  55. "Product Information. Vivelle (estradiol)." Ciba Pharmaceuticals, Summit, NJ.
  56. "Product Information. Ortho Dienestrol Cream (dienestrol topical)" Ortho McNeil Pharmaceutical, Raritan, NJ.
  57. "Product Information. Premarin (conjugated estrogens)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
View all 57 references
Major

Estrogens (Includes Ena) ↔ Hypercalcemia In Breast Cancer

Severe Potential Hazard, Moderate plausibility

Applies to: Breast Cancer

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.

References

  1. "Product Information. Climara (estradiol)." Berlex, Richmond, CA.
  2. "Product Information. Estrace (estradiol)." Warner Chilcott Laboratories, Rockaway, NJ.
  3. "Product Information. Ogen (estropipate topical)" Pharmacia and Upjohn, Kalamazoo, MI.
  4. "Product Information. Ortho-Est (estropipate)." Ortho McNeil Pharmaceutical, Raritan, NJ.
  5. "Product Information. Ortho Dienestrol Cream (dienestrol topical)" Ortho McNeil Pharmaceutical, Raritan, NJ.
  6. "Product Information. Premarin (conjugated estrogens)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  7. "Product Information. Vivelle (estradiol)." Ciba Pharmaceuticals, Summit, NJ.
  8. "Product Information. Emcyt (estramustine)." Pharmacia and Upjohn, Kalamazoo, MI.
  9. "Product Information. Estraderm (estradiol)." Ciba Pharmaceuticals, Summit, NJ.
  10. "Product Information. Estratab (esterified estrogens)" Solvay Pharmaceuticals Inc, Marietta, GA.
  11. "Product Information. Estinyl Tablets (ethinyl estradiol)" Schering Corporation, Kenilworth, NJ.
View all 11 references
Major

Estrogens (Includes Ena) ↔ Hypertension

Severe Potential Hazard, High plausibility

Applies to: Hypertension

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.

References

  1. 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
  2. Crane MG, Harris JJ, Winsor W 3d "Hypertension, oral contraceptive agents, and conjugated estrogens." Ann Intern Med 74 (1971): 13-21
  3. "Product Information. Ogen (estropipate topical)" Pharmacia and Upjohn, Kalamazoo, MI.
  4. "Product Information. Climara (estradiol)." Berlex, Richmond, CA.
  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. Thorneycroft IH "Oral contraceptives and myocardial infarction." Am J Obstet Gynecol 163 (1990): 1393-7
  7. Steinberg WM "Oral contraception: risks and benefits." Adv Contracept 5 (1989): 219-28
  8. Martinelli I, Rosendaal FR, Vandenbroucke JP, Mannucci PM "Oral contraceptives are a risk factor for cerebral vein thrombosis." Thromb Haemost 76 (1996): 477-8
  9. "Product Information. Ortho Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  10. "Product Information. Estraderm (estradiol)." Ciba Pharmaceuticals, Summit, NJ.
  11. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  12. 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
  13. Thorogood M "Risk of stroke in users of oral contraceptives." JAMA 281 (1999): 1255-6
  14. "Product Information. Vivelle (estradiol)." Ciba Pharmaceuticals, Summit, NJ.
  15. 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
  16. 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
  17. Lidegaard O "Oral contraception and risk of a cerebral thromboembolic attack: results of a case-control study." BMJ 306 (1993): 956-63
  18. "Product Information. Premarin (conjugated estrogens)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  19. "Product Information. Ortho Novum 1/50 (mestranol-norethindrone)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  20. "Product Information. Ortho Dienestrol Cream (dienestrol topical)" Ortho McNeil Pharmaceutical, Raritan, NJ.
  21. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  22. Leiman G "Depo-medroxyprogesterone acetate as a contraceptive agent: its effect on weight and blood pressure." Am J Obstet Gynecol 114 (1972): 97-102
  23. 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
  24. Peterson HB, Lee NC "Long-term health risks and benefits of oral contraceptive use." Obstet Gynecol Clin North Am 17 (1990): 775-88
  25. 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
  26. Derman RJ "Oral contraceptives and cardiovascular risk. Taking a safe course of action." Postgrad Med 88 (1990): 119-22
  27. Williams RS "Benefits and risks of oral contraceptive use." Postgrad Med 92 (1992): 155-7
  28. "Product Information. Ortho-Est (estropipate)." Ortho McNeil Pharmaceutical, Raritan, NJ.
  29. "Product Information. Demulen (ethinyl estradiol-ethynodiol)." Searle, Skokie, IL.
  30. "Product Information. Estinyl Tablets (ethinyl estradiol)" Schering Corporation, Kenilworth, NJ.
  31. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  32. 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
  33. Piegsa K, Guillebaud J "Oral contraceptives and the risk of DVT." Practitioner 240 (1996): 544
  34. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  35. 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
  36. 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
  37. 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
  38. "Product Information. Estratab (esterified estrogens)" Solvay Pharmaceuticals Inc, Marietta, GA.
  39. Barrett-Connor E, Bush TL "Estrogen and coronary heart disease in women." JAMA 265 (1991): 1861-7
  40. Wren BG, Routledge DA "Blood pressure changes: oestrogens in climacteric women." Med J Aust 2 (1981): 528-31
  41. Mishell DR "Contraception." N Engl J Med 320 (1989): 777-85
  42. Jick H, Dinan B, Rothman KJ "Noncontraceptive estrogens and nonfatal myocardial infarction." JAMA 239 (1978): 1407-8
  43. 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
  44. Belchetz PE "Hormonal treatment of postmenopausal women." N Engl J Med 330 (1994): 1062-71
  45. Speroff L "Oral contraceptives and venous thromboembolism." Int J Gynaecol Obstet 54 (1996): 45-50
  46. 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
  47. 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
  48. 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
  49. 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
  50. Derman R "Oral contraceptives: a reassessment." Obstet Gynecol Surv 44 (1989): 662-8
  51. "Product Information. Estrace (estradiol)." Warner Chilcott Laboratories, Rockaway, NJ.
  52. Rosenberg L, Palmer JR, Lesko SM, Shapiro S "Oral contraceptive use and the risk of myocardial infarction." Am J Epidemiol 131 (1990): 1009-16
View all 52 references
Major

Estrogens (Includes Ena) ↔ Thromboembolism/Cardiovascular

Severe Potential Hazard, High plausibility

Applies to: Thrombotic/Thromboembolic Disorder, Cerebral Vascular Disorder, History - Thrombotic/Thromboembolic Disorder, Ischemic Heart Disease

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. 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.

References

  1. "Product Information. Estraderm (estradiol)." Ciba Pharmaceuticals, Summit, NJ.
  2. Thorogood M "Risk of stroke in users of oral contraceptives." JAMA 281 (1999): 1255-6
  3. 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
  4. Mishell DR "Contraception." N Engl J Med 320 (1989): 777-85
  5. "Product Information. Estratab (esterified estrogens)" Solvay Pharmaceuticals Inc, Marietta, GA.
  6. Mendelsohn ME, Karas RH "The protective effects of estrogen on the cardiovascular system." N Engl J Med 340 (1999): 1801-11
  7. 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
  8. "Product Information. Ortho Novum 1/50 (mestranol-norethindrone)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  9. "Product Information. Premarin (conjugated estrogens)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  10. "Product Information. Ortho Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  11. 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
  12. Lidegaard O "Oral contraception and risk of a cerebral thromboembolic attack: results of a case-control study." BMJ 306 (1993): 956-63
  13. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  14. "Product Information. Estrace (estradiol)." Warner Chilcott Laboratories, Rockaway, NJ.
  15. 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
  16. "Product Information. Estinyl Tablets (ethinyl estradiol)" Schering Corporation, Kenilworth, NJ.
  17. "Product Information. Demulen (ethinyl estradiol-ethynodiol)." Searle, Skokie, IL.
  18. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  19. Speroff L "Oral contraceptives and venous thromboembolism." Int J Gynaecol Obstet 54 (1996): 45-50
  20. Williams RS "Benefits and risks of oral contraceptive use." Postgrad Med 92 (1992): 155-7
  21. 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
  22. 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
  23. "Product Information. Ortho-Est (estropipate)." Ortho McNeil Pharmaceutical, Raritan, NJ.
  24. 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
  25. 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
  26. 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
  27. Belchetz PE "Hormonal treatment of postmenopausal women." N Engl J Med 330 (1994): 1062-71
  28. Miwa LJ, Edmunds AL, Shaefer MS, Raynor SC "Idiopathic thromboembolism associated with triphasic oral contraceptives." DICP 23 (1989): 773-5
  29. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  30. Thorneycroft IH "Oral contraceptives and myocardial infarction." Am J Obstet Gynecol 163 (1990): 1393-7
  31. 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
  32. 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
  33. Rosenberg L, Palmer JR, Lesko SM, Shapiro S "Oral contraceptive use and the risk of myocardial infarction." Am J Epidemiol 131 (1990): 1009-16
  34. 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
  35. 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
  36. 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
  37. Meade TW "Oral contraceptives, clotting factors, and thrombosis." Am J Obstet Gynecol 142 (1982): 758-61
  38. 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
  39. 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
  40. Derman RJ "Oral contraceptives and cardiovascular risk. Taking a safe course of action." Postgrad Med 88 (1990): 119-22
  41. Peterson HB, Lee NC "Long-term health risks and benefits of oral contraceptive use." Obstet Gynecol Clin North Am 17 (1990): 775-88
  42. "Product Information. Ortho Dienestrol Cream (dienestrol topical)" Ortho McNeil Pharmaceutical, Raritan, NJ.
  43. 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
  44. Notelovitz M "Oral contraception and coagulation." Clin Obstet Gynecol 28 (1985): 73-83
  45. "Product Information. Vivelle (estradiol)." Ciba Pharmaceuticals, Summit, NJ.
  46. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  47. 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
  48. 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
  49. 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
  50. Key JD, Hammill WW, Everett L "Pulmonary embolus in an adolescent on oral contraceptives." J Adolesc Health 13 (1992): 713-5
  51. Petitti DB "Hormone replacement therapy and heart disease prevention: experimentation trumps observation." JAMA 280 (1998): 650-2
  52. Piegsa K, Guillebaud J "Oral contraceptives and the risk of DVT." Practitioner 240 (1996): 544
  53. Steinberg WM "Oral contraception: risks and benefits." Adv Contracept 5 (1989): 219-28
  54. Barrett-Connor E, Bush TL "Estrogen and coronary heart disease in women." JAMA 265 (1991): 1861-7
  55. Burkman RT Jr "Benefits and risk of oral contraceptives. A reassessment." J Reprod Med 36 (1991): 217-8
  56. Martinelli I, Rosendaal FR, Vandenbroucke JP, Mannucci PM "Oral contraceptives are a risk factor for cerebral vein thrombosis." Thromb Haemost 76 (1996): 477-8
  57. 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
  58. Jick H, Dinan B, Rothman KJ "Noncontraceptive estrogens and nonfatal myocardial infarction." JAMA 239 (1978): 1407-8
  59. "Product Information. Ogen (estropipate topical)" Pharmacia and Upjohn, Kalamazoo, MI.
  60. "Product Information. Climara (estradiol)." Berlex, Richmond, CA.
View all 60 references
Major

Estrogens/Progestogens (Includes Ena) ↔ Hepatic Neoplasms

Severe Potential Hazard, High plausibility

Applies to: Hepatic Tumor, Hepatic Tumor

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.

References

  1. 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
  2. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  3. "Product Information. Demulen (ethinyl estradiol-ethynodiol)." Searle, Skokie, IL.
  4. "Product Information. Ortho-Est (estropipate)." Ortho McNeil Pharmaceutical, Raritan, NJ.
  5. "Product Information. Micronor (norethindrone)" Ortho McNeil Pharmaceutical, Raritan, NJ.
  6. "Product Information. Estinyl Tablets (ethinyl estradiol)" Schering Corporation, Kenilworth, NJ.
  7. "Product Information. Ovrette (norgestrel)" Wyeth-Ayerst Laboratories, Philadelphia, PA.
  8. "Product Information. Premarin (conjugated estrogens)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  9. "Product Information. Vivelle (estradiol)." Ciba Pharmaceuticals, Summit, NJ.
  10. 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
  11. "Product Information. Ortho Dienestrol Cream (dienestrol topical)" Ortho McNeil Pharmaceutical, Raritan, NJ.
  12. "Product Information. Estraderm (estradiol)." Ciba Pharmaceuticals, Summit, NJ.
  13. "Product Information. Estratab (esterified estrogens)" Solvay Pharmaceuticals Inc, Marietta, GA.
  14. 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
  15. Mishell DR "Contraception." N Engl J Med 320 (1989): 777-85
  16. Mathieu D, Zafrani ES, Anglade MC, Dhumeaux D "Association of focal nodular hyperplasia and hepatic hemangioma." Gastroenterology 97 (1989): 154-7
  17. "Product Information. Norplant System (levonorgestrel)" Wyeth-Ayerst Laboratories, Philadelphia, PA.
  18. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  19. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  20. Mooney MJ, Nyreen MR, Hall RA, Carter PL "Hepatic adenoma presenting as a right lower quadrant mass." Am Surg 59 (1993): 229-31
  21. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  22. "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
  23. "Oral contraceptives and neoplasia. WHO Scientific Group." World Health Organ Tech Rep Ser 817 (1992): 1-46
  24. "Product Information. Ortho Novum 1/50 (mestranol-norethindrone)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  25. 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
  26. 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
  27. "Product Information. Estrace (estradiol)." Warner Chilcott Laboratories, Rockaway, NJ.
  28. Conter RL, Longmire WP Jr "Recurrent hepatic hemangiomas. Possible association with estrogen therapy." Ann Surg 207 (1988): 115-9
  29. Tao LC "Oral contraceptive-associated liver cell adenoma and hepatocellular carcinoma." Cancer 68 (1991): 341-7
  30. "Product Information. Ortho Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  31. "Product Information. Climara (estradiol)." Berlex, Richmond, CA.
  32. "Product Information. Ogen (estropipate topical)" Pharmacia and Upjohn, Kalamazoo, MI.
View all 32 references
Major

Progestogens (Includes Ena) ↔ Breast Malignancy

Severe Potential Hazard, High plausibility

Applies to: Breast Cancer

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.

References

  1. "Product Information. Micronor (norethindrone)" Ortho McNeil Pharmaceutical, Raritan, NJ.
  2. Jordan A "Toxicology of depot medroxyprogesterone acetate." Contraception 49 (1994): 189-201
  3. Skegg DC, Noonan EA, Paul C, Spears GF, Meirik O, Thomas DB "Depot medroxyprogesterone acetate and breast cancer." JAMA 273 (1995): 799-807
  4. "Breast cancer and depot-medroxyprogesterone acetate: a multinational study. WHO Collaborative Study of Neoplasia and Steroid Contraceptives" Lancet 338 (1991): 833-8
  5. "Product Information. Ovrette (norgestrel)" Wyeth-Ayerst Laboratories, Philadelphia, PA.
  6. "Product Information. Depo-Provera (medroxyprogesterone)." Pharmacia and Upjohn, Kalamazoo, MI.
  7. 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
  8. Chilvers C "Breast cancer and depot-medroxyprogesterone acetate - a review." Contraception 49 (1994): 211-22
  9. "Breast cancer, cervical cancer, and depot medroxyprogesterone acetate. WHO Collaborative Study of Neoplasia and Steroid Contraceptives" Lancet 2 (1984): 1207-8
  10. "Product Information. Provera (medroxyprogesterone)." Pharmacia and Upjohn, Kalamazoo, MI.
  11. "Product Information. Norplant System (levonorgestrel)" Wyeth-Ayerst Laboratories, Philadelphia, PA.
View all 11 references
Major

Progestogens (Includes Ena) ↔ Liver Disease

Severe Potential Hazard, High plausibility

Applies to: Liver Disease

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.

References

  1. 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
  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. "Product Information. Norplant System (levonorgestrel)" Wyeth-Ayerst Laboratories, Philadelphia, PA.
  4. "Product Information. Provera (medroxyprogesterone)." Pharmacia and Upjohn, Kalamazoo, MI.
  5. "Product Information. Micronor (norethindrone)" Ortho McNeil Pharmaceutical, Raritan, NJ.
  6. "Product Information. Ovrette (norgestrel)" Wyeth-Ayerst Laboratories, Philadelphia, PA.
  7. 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
  8. 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
  9. Hendeles SM, Galand N, Schwers J "Metabolism of orally administered D-norgestrel in women." Acta Endocrinol (Copenh) 71 (1972): 557-68
  10. "Product Information. Depo-Provera (medroxyprogesterone)." Pharmacia and Upjohn, Kalamazoo, MI.
View all 10 references
Major

Progestogens (Includes Ena) ↔ Thromboembolism

Severe Potential Hazard, Moderate plausibility

Applies to: Cerebral Vascular Disorder, History - Thrombotic/Thromboembolic Disorder, Thrombotic/Thromboembolic Disorder

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.

References

  1. "Product Information. Depo-Provera (medroxyprogesterone)." Pharmacia and Upjohn, Kalamazoo, MI.
  2. "Product Information. Provera (medroxyprogesterone)." Pharmacia and Upjohn, Kalamazoo, MI.
  3. "Product Information. Megace (megestrol)." Bristol-Myers Squibb, Princeton, NJ.
  4. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  5. 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
  6. "Product Information. Norplant System (levonorgestrel)" Wyeth-Ayerst Laboratories, Philadelphia, PA.
  7. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  8. 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
  9. "Product Information. Demulen (ethinyl estradiol-ethynodiol)." Searle, Skokie, IL.
  10. 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
  11. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  12. "Product Information. Ortho Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  13. "Product Information. Ovrette (norgestrel)" Wyeth-Ayerst Laboratories, Philadelphia, PA.
  14. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  15. "Product Information. Micronor (norethindrone)" Ortho McNeil Pharmaceutical, Raritan, NJ.
View all 15 references
Moderate

Estrogens (Includes Ena) ↔ Angioedema

Moderate Potential Hazard, Moderate plausibility

Applies to: Angioedema

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.

Moderate

Estrogens (Includes Ena) ↔ Gallbladder Disease

Moderate Potential Hazard, Moderate plausibility

Applies to: Gallbladder Disease

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.

References

  1. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  2. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  3. "Product Information. Ortho Dienestrol Cream (dienestrol topical)" Ortho McNeil Pharmaceutical, Raritan, NJ.
  4. "Product Information. Ortho Novum 1/50 (mestranol-norethindrone)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  5. "Product Information. Vivelle (estradiol)." Ciba Pharmaceuticals, Summit, NJ.
  6. "Product Information. Premarin (conjugated estrogens)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  7. "Product Information. Climara (estradiol)." Berlex, Richmond, CA.
  8. 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
  9. "Product Information. Ogen (estropipate topical)" Pharmacia and Upjohn, Kalamazoo, MI.
  10. "Product Information. Ortho Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  11. "Product Information. Estratab (esterified estrogens)" Solvay Pharmaceuticals Inc, Marietta, GA.
  12. "Product Information. Estraderm (estradiol)." Ciba Pharmaceuticals, Summit, NJ.
  13. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  14. "Product Information. Estrace (estradiol)." Warner Chilcott Laboratories, Rockaway, NJ.
  15. "Product Information. Ortho-Est (estropipate)." Ortho McNeil Pharmaceutical, Raritan, NJ.
  16. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  17. "Product Information. Demulen (ethinyl estradiol-ethynodiol)." Searle, Skokie, IL.
  18. "Product Information. Estinyl Tablets (ethinyl estradiol)" Schering Corporation, Kenilworth, NJ.
View all 18 references
Moderate

Estrogens (Includes Ena) ↔ Hypercalcemia

Moderate Potential Hazard, Moderate plausibility

Applies to: Hyperparathyroidism, Renal Dysfunction, Hypercalcemia

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.

References

  1. "Product Information. Estrace (estradiol)." Warner Chilcott Laboratories, Rockaway, NJ.
  2. "Product Information. Climara (estradiol)." Berlex, Richmond, CA.
  3. "Product Information. Emcyt (estramustine)." Pharmacia and Upjohn, Kalamazoo, MI.
  4. "Product Information. Estraderm (estradiol)." Ciba Pharmaceuticals, Summit, NJ.
  5. "Product Information. Vivelle (estradiol)." Ciba Pharmaceuticals, Summit, NJ.
  6. "Product Information. Premarin (conjugated estrogens)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
View all 6 references
Moderate

Estrogens (Includes Ena) ↔ Hyperlipidemia

Moderate Potential Hazard, Moderate plausibility

Applies to: Hyperlipidemia

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.

References

  1. "Product Information. Estrace (estradiol)." Warner Chilcott Laboratories, Rockaway, NJ.
  2. 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
  3. 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
  4. "Product Information. Estinyl Tablets (ethinyl estradiol)" Schering Corporation, Kenilworth, NJ.
  5. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  6. "Product Information. Demulen (ethinyl estradiol-ethynodiol)." Searle, Skokie, IL.
  7. "Product Information. Ortho-Est (estropipate)." Ortho McNeil Pharmaceutical, Raritan, NJ.
  8. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  9. 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
  10. "Product Information. Vivelle (estradiol)." Ciba Pharmaceuticals, Summit, NJ.
  11. "Product Information. Ortho Dienestrol Cream (dienestrol topical)" Ortho McNeil Pharmaceutical, Raritan, NJ.
  12. "Product Information. Ortho Novum 1/50 (mestranol-norethindrone)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  13. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  14. "Product Information. Estraderm (estradiol)." Ciba Pharmaceuticals, Summit, NJ.
  15. "Product Information. Ortho Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  16. "Product Information. Estratab (esterified estrogens)" Solvay Pharmaceuticals Inc, Marietta, GA.
  17. Derman R "Oral contraceptives: a reassessment." Obstet Gynecol Surv 44 (1989): 662-8
  18. "Product Information. Climara (estradiol)." Berlex, Richmond, CA.
  19. Steinberg WM "Oral contraception: risks and benefits." Adv Contracept 5 (1989): 219-28
  20. Molitch ME, Oill P, Odell WD "Massive hyperlipemia during estrogen therapy." JAMA 227 (1974): 522-5
  21. "Product Information. Ogen (estropipate topical)" Pharmacia and Upjohn, Kalamazoo, MI.
  22. "Product Information. Premarin (conjugated estrogens)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  23. 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
  24. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho Pharmaceutical Corporation, Raritan, NJ.
View all 24 references
Moderate

Estrogens (Includes Ena) ↔ Liver Disease

Moderate Potential Hazard, High plausibility

Applies to: Liver Disease

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.

References

  1. "Product Information. Ortho Novum 1/50 (mestranol-norethindrone)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  2. "Product Information. Climara (estradiol)." Berlex, Richmond, CA.
  3. "Product Information. Ogen (estropipate topical)" Pharmacia and Upjohn, Kalamazoo, MI.
  4. "Product Information. Ortho Dienestrol Cream (dienestrol topical)" Ortho McNeil Pharmaceutical, Raritan, NJ.
  5. Adlercrueuta H "Hepatic metabolism of estrogens in health and disease." N Engl J Med 290 (1974): 1081-3
  6. "Product Information. Vivelle (estradiol)." Ciba Pharmaceuticals, Summit, NJ.
  7. "Product Information. Premarin (conjugated estrogens)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  8. "Product Information. Estraderm (estradiol)." Ciba Pharmaceuticals, Summit, NJ.
  9. 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
  10. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  11. "Product Information. Emcyt (estramustine)." Pharmacia and Upjohn, Kalamazoo, MI.
  12. "Product Information. Ortho Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  13. "Product Information. Estrace (estradiol)." Warner Chilcott Laboratories, Rockaway, NJ.
  14. 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
  15. "Product Information. Ortho-Est (estropipate)." Ortho McNeil Pharmaceutical, Raritan, NJ.
  16. "Product Information. Demulen (ethinyl estradiol-ethynodiol)." Searle, Skokie, IL.
  17. "Product Information. Estinyl Tablets (ethinyl estradiol)" Schering Corporation, Kenilworth, NJ.
  18. Goldzieher JW "Pharmacology of contraceptive steroids: a brief review." Am J Obstet Gynecol 160 (1989): 1260-4
  19. "Product Information. Estratab (esterified estrogens)" Solvay Pharmaceuticals Inc, Marietta, GA.
  20. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  21. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  22. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho Pharmaceutical Corporation, Raritan, NJ.
View all 22 references
Moderate

Estrogens (Includes Ena) ↔ Melasma

Moderate Potential Hazard, Moderate plausibility

Applies to: Melasma

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.

Moderate

Estrogens/Progestogens (Includes Ena) ↔ Depression

Moderate Potential Hazard, Moderate plausibility

Applies to: Depression, Depression

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.

References

  1. "Product Information. Estinyl Tablets (ethinyl estradiol)" Schering Corporation, Kenilworth, NJ.
  2. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  3. "Product Information. Ortho-Est (estropipate)." Ortho McNeil Pharmaceutical, Raritan, NJ.
  4. "Product Information. Estratab (esterified estrogens)" Solvay Pharmaceuticals Inc, Marietta, GA.
  5. "Product Information. Micronor (norethindrone)" Ortho McNeil Pharmaceutical, Raritan, NJ.
  6. "Product Information. Demulen (ethinyl estradiol-ethynodiol)." Searle, Skokie, IL.
  7. "Product Information. Ogen (estropipate topical)" Pharmacia and Upjohn, Kalamazoo, MI.
  8. "Product Information. Climara (estradiol)." Berlex, Richmond, CA.
  9. "Product Information. Provera (medroxyprogesterone)." Pharmacia and Upjohn, Kalamazoo, MI.
  10. "Product Information. Norplant System (levonorgestrel)" Wyeth-Ayerst Laboratories, Philadelphia, PA.
  11. "Product Information. Ortho Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  12. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  13. "Product Information. Ovrette (norgestrel)" Wyeth-Ayerst Laboratories, Philadelphia, PA.
  14. "Product Information. Estraderm (estradiol)." Ciba Pharmaceuticals, Summit, NJ.
  15. "Product Information. Ortho Dienestrol Cream (dienestrol topical)" Ortho McNeil Pharmaceutical, Raritan, NJ.
  16. "Product Information. Premarin (conjugated estrogens)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  17. "Product Information. Depo-Provera (medroxyprogesterone)." Pharmacia and Upjohn, Kalamazoo, MI.
  18. "Product Information. Ortho Novum 1/50 (mestranol-norethindrone)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  19. "Product Information. Vivelle (estradiol)." Ciba Pharmaceuticals, Summit, NJ.
  20. "Product Information. Estrace (estradiol)." Warner Chilcott Laboratories, Rockaway, NJ.
  21. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  22. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho Pharmaceutical Corporation, Raritan, NJ.
View all 22 references
Moderate

Estrogens/Progestogens (Includes Ena) ↔ Fluid Retention

Moderate Potential Hazard, Moderate plausibility

Applies to: Fluid Retention, Asthma, Renal Dysfunction, Seizures, Congestive Heart Failure, Migraine, Fluid Retention, Congestive Heart Failure, Migraine, Renal Dysfunction, Seizures, Asthma, Hypertension

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.

References

  1. "Product Information. Estrace (estradiol)." Warner Chilcott Laboratories, Rockaway, NJ.
  2. "Product Information. Micronor (norethindrone)" Ortho McNeil Pharmaceutical, Raritan, NJ.
  3. "Product Information. Demulen (ethinyl estradiol-ethynodiol)." Searle, Skokie, IL.
  4. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  5. "Product Information. Norplant System (levonorgestrel)" Wyeth-Ayerst Laboratories, Philadelphia, PA.
  6. "Product Information. Climara (estradiol)." Berlex, Richmond, CA.
  7. "Product Information. Provera (medroxyprogesterone)." Pharmacia and Upjohn, Kalamazoo, MI.
  8. "Product Information. Megace (megestrol)." Bristol-Myers Squibb, Princeton, NJ.
  9. "Product Information. Depo-Provera (medroxyprogesterone)." Pharmacia and Upjohn, Kalamazoo, MI.
  10. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  11. "Product Information. Emcyt (estramustine)." Pharmacia and Upjohn, Kalamazoo, MI.
  12. "Product Information. Ortho Novum 1/50 (mestranol-norethindrone)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  13. Leiman G "Depo-medroxyprogesterone acetate as a contraceptive agent: its effect on weight and blood pressure." Am J Obstet Gynecol 114 (1972): 97-102
  14. "Product Information. Ortho Dienestrol Cream (dienestrol topical)" Ortho McNeil Pharmaceutical, Raritan, NJ.
  15. "Product Information. Premarin (conjugated estrogens)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  16. "Product Information. Ogen (estropipate topical)" Pharmacia and Upjohn, Kalamazoo, MI.
  17. "Product Information. Vivelle (estradiol)." Ciba Pharmaceuticals, Summit, NJ.
  18. "Product Information. Ortho-Est (estropipate)." Ortho McNeil Pharmaceutical, Raritan, NJ.
  19. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  20. "Product Information. Estinyl Tablets (ethinyl estradiol)" Schering Corporation, Kenilworth, NJ.
  21. "Product Information. Estratab (esterified estrogens)" Solvay Pharmaceuticals Inc, Marietta, GA.
  22. "Product Information. Estraderm (estradiol)." Ciba Pharmaceuticals, Summit, NJ.
  23. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  24. "Product Information. Ortho Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  25. "Product Information. Ovrette (norgestrel)" Wyeth-Ayerst Laboratories, Philadelphia, PA.
View all 25 references
Moderate

Estrogens/Progestogens (Includes Ena) ↔ Glucose Intolerance

Moderate Potential Hazard, Moderate plausibility

Applies to: Diabetes Mellitus, Diabetes Mellitus

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.

References

  1. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  2. Stubblefield PG "Choosing the best oral contraceptive." Clin Obstet Gynecol 32 (1989): 316-28
  3. "Product Information. Norplant System (levonorgestrel)" Wyeth-Ayerst Laboratories, Philadelphia, PA.
  4. Hannaford PC, Kay CR "Oral contraceptives and diabetes mellitus." BMJ 299 (1989): 1315-6
  5. Belchetz PE "Hormonal treatment of postmenopausal women." N Engl J Med 330 (1994): 1062-71
  6. Steinberg WM "Oral contraception: risks and benefits." Adv Contracept 5 (1989): 219-28
  7. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  8. "Product Information. Ortho-Novum (oral contraceptive combination pill)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  9. Derman R "Oral contraceptives: a reassessment." Obstet Gynecol Surv 44 (1989): 662-8
  10. "Product Information. Ovrette (norgestrel)" Wyeth-Ayerst Laboratories, Philadelphia, PA.
  11. 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
  12. "Product Information. Demulen (ethinyl estradiol-ethynodiol)." Searle, Skokie, IL.
  13. Kaunitz AM "Long-acting injectable contraception with depot medroxyprogesterone acetate." Am J Obstet Gynecol 170 (1994): 1543-9
  14. 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
  15. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  16. 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
  17. 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
  18. 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
  19. 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
  20. "Product Information. Ortho Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  21. "Product Information. Ortho Novum 1/50 (mestranol-norethindrone)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  22. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  23. "Product Information. Micronor (norethindrone)" Ortho McNeil Pharmaceutical, Raritan, NJ.
View all 23 references
Moderate

Estrogens/Progestogens (Includes Ena) ↔ Retinal Thrombosis

Moderate Potential Hazard, Moderate plausibility

Applies to: Visual Defect/Disturbance, Visual Defect/Disturbance

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.

Moderate

Estrogens/Progestogens (Includes Ena) ↔ Thyroid Function Tests

Moderate Potential Hazard, Moderate plausibility

Applies to: Thyroid Disease, Thyroid Disease

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.

References

  1. "Product Information. Ortho Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  2. "Product Information. Ortho-Est (estropipate)." Ortho McNeil Pharmaceutical, Raritan, NJ.
  3. "Product Information. Estinyl Tablets (ethinyl estradiol)" Schering Corporation, Kenilworth, NJ.
  4. "Product Information. Micronor (norethindrone)" Ortho McNeil Pharmaceutical, Raritan, NJ.
  5. "Product Information. Estrace (estradiol)." Warner Chilcott Laboratories, Rockaway, NJ.
  6. "Product Information. Deltasone (prednisone)." Pharmacia and Upjohn, Kalamazoo, MI.
  7. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  8. "Product Information. Estratab (esterified estrogens)" Solvay Pharmaceuticals Inc, Marietta, GA.
  9. "Product Information. Estraderm (estradiol)." Ciba Pharmaceuticals, Summit, NJ.
  10. "Product Information. Climara (estradiol)." Berlex, Richmond, CA.
  11. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  12. "Product Information. Depo-Provera (medroxyprogesterone)." Pharmacia and Upjohn, Kalamazoo, MI.
  13. "Product Information. Emcyt (estramustine)." Pharmacia and Upjohn, Kalamazoo, MI.
  14. "Product Information. Ovrette (norgestrel)" Wyeth-Ayerst Laboratories, Philadelphia, PA.
  15. "Product Information. Ortho Novum 1/50 (mestranol-norethindrone)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  16. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  17. "Product Information. Ogen (estropipate topical)" Pharmacia and Upjohn, Kalamazoo, MI.
  18. "Product Information. Demulen (ethinyl estradiol-ethynodiol)." Searle, Skokie, IL.
  19. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  20. "Product Information. Norplant System (levonorgestrel)" Wyeth-Ayerst Laboratories, Philadelphia, PA.
  21. "Product Information. Provera (medroxyprogesterone)." Pharmacia and Upjohn, Kalamazoo, MI.
  22. "Product Information. Premarin (conjugated estrogens)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  23. "Product Information. Ortho Dienestrol Cream (dienestrol topical)" Ortho McNeil Pharmaceutical, Raritan, NJ.
  24. "Product Information. Vivelle (estradiol)." Ciba Pharmaceuticals, Summit, NJ.
View all 24 references
Moderate

Progestogens (Includes Ena) ↔ Hyperlipidemia

Moderate Potential Hazard, Moderate plausibility

Applies to: Hyperlipidemia

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.

References

  1. "Product Information. Provera (medroxyprogesterone)." Pharmacia and Upjohn, Kalamazoo, MI.
  2. 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
  3. "Product Information. Norplant System (levonorgestrel)" Wyeth-Ayerst Laboratories, Philadelphia, PA.
  4. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  5. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  6. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  7. 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
  8. 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
  9. "Product Information. Demulen (ethinyl estradiol-ethynodiol)." Searle, Skokie, IL.
  10. Teichmann AT, Wander HE, Cremer P, et al. "Medroxyprogesterone acetate and lipid metabolic changes." Arzneimittelforschung 37 (1987): 573-77
  11. "Product Information. Ortho Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  12. "Product Information. Micronor (norethindrone)" Ortho McNeil Pharmaceutical, Raritan, NJ.
  13. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  14. 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
  15. "Product Information. Ovrette (norgestrel)" Wyeth-Ayerst Laboratories, Philadelphia, PA.
  16. "Product Information. Depo-Provera (medroxyprogesterone)." Pharmacia and Upjohn, Kalamazoo, MI.
  17. 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
View all 17 references
Moderate

Progestogens (Includes Ena) ↔ Weight Gain

Minor Potential Hazard, Moderate plausibility

Applies to: Obesity

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.

References

  1. "Product Information. Lo/Ovral (ethinyl estradiol-norgestrel)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  2. "Product Information. Demulen (ethinyl estradiol-ethynodiol)." Searle, Skokie, IL.
  3. "Product Information. Ortho Novum 10/11 (ethinyl estradiol-norethindrone)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  4. "Product Information. Micronor (norethindrone)" Ortho McNeil Pharmaceutical, Raritan, NJ.
  5. "Product Information. Depo-Provera (medroxyprogesterone)." Pharmacia and Upjohn, Kalamazoo, MI.
  6. "Product Information. Triphasil (ethinyl estradiol-levonorgestrel)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  7. "Product Information. Ovrette (norgestrel)" Wyeth-Ayerst Laboratories, Philadelphia, PA.
  8. Leiman G "Depo-medroxyprogesterone acetate as a contraceptive agent: its effect on weight and blood pressure." Am J Obstet Gynecol 114 (1972): 97-102
  9. "Product Information. Ortho-Cept (desogestrel-ethinyl estradiol)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  10. "Product Information. Norplant System (levonorgestrel)" Wyeth-Ayerst Laboratories, Philadelphia, PA.
  11. "Product Information. Ortho-Cyclen (ethinyl estradiol-norgestimate)." Ortho Pharmaceutical Corporation, Raritan, NJ.
  12. Amatayakul K, Sivasomboon B, Thanangkul O "A study of the mechanism of weight gain in medroxyprogesterone acetate users." Contraception 22 (1980): 605-22
  13. "Product Information. Provera (medroxyprogesterone)." Pharmacia and Upjohn, Kalamazoo, MI.
View all 13 references

Ena (estradiol / norethindrone) drug Interactions

There are 344 drug interactions with Ena (estradiol / norethindrone)

Ena (estradiol / norethindrone) alcohol/food Interactions

There are 7 alcohol/food interactions with Ena (estradiol / norethindrone)

Drug Interaction Classification

The classifications below are a general guideline only. It is difficult to determine the relevance of a particular drug interaction to any individual given the large number of variables.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No information available.

Do not stop taking any medications without consulting your healthcare provider.

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