Skip to main content

Conjugated estrogens Side Effects

Medically reviewed by Last updated on Jun 13, 2024.

Applies to conjugated estrogens: oral tablet. Other dosage forms:


Oral route (Tablet)

Endometrial Cancer, Cardiovascular Disorders, Breast Cancer and Probable DementiaEstrogen-Alone TherapyThere is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens.Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or dementia.Women's Health Initiative estrogen-alone substudy reported increased risks of stroke and deep vein thrombosis.The Women’s Health Initiative Memory Study estrogen-alone ancillary study of Women’s Health Initiative reported an increased risk of probable dementia in postmenopausal women 65 years of age and older.Estrogen Plus Progestin TherapyEstrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia.The Women’s Health Initiative estrogen plus progestin substudy reported increased risks of stroke, DVT, pulmonary embolism, and myocardial infarction.The Women’s Health Initiative estrogen plus progestin substudy reported increased risks of invasive breast cancer.The Women’s Health Initiative Memory Study estrogen plus progestin ancillary study of Women’s Health Initiative reported an increased risk of probable dementia in postmenopausal women 65 years of age and older.

Serious side effects

Along with its needed effects, conjugated estrogens may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking conjugated estrogens:

More common

Less common

Incidence not known

Other side effects

Some side effects of conjugated estrogens may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

Less common

Incidence not known

For Healthcare Professionals

Applies to conjugated estrogens: injectable powder for injection, oral tablet, vaginal cream.


Common (1% to 10%): Hypertension, palpitation, vasodilation

Rare (less than 0.1%): Stroke

Postmarketing reports: Deep and superficial venous thrombosis, pulmonary embolism, thrombophlebitis, myocardial infarction, stroke[Ref]

-HRT is associated with a 1.3 to 3-fold increased relative risk of developing VTE, i.e., deep vein thrombosis or pulmonary embolism. This event is more likely to occur in the first year of using HRT.

-The use of estrogen-only and estrogen-progestin therapy is associated with an up to 1.5 fold increased relative risk of ischemic stroke.

-The risk of hemorrhagic stroke is not increased during use of HRT. This relative risk is not dependent on age or on duration of use, but as the baseline risk is strongly age-dependent, the overall risk of stroke in women who use HRT will increase with age.[Ref]


Common (1% to 10%): Acne, alopecia, hirsutism, pruritus, rash, skin discoloration, sweating, fungal dermatitis

Postmarketing reports: Chloasma or melasma (may persist when drug is discontinued), erythema multiforme, erythema nodosum, loss of scalp hair[Ref]


Common (1% to 10%): Constipation, diarrhea, dyspepsia, eructation, flatulence, nausea

Uncommon (0.1% to 1%): Bloating, abdominal pain

Postmarketing reports: Vomiting, abdominal discomfort, abdominal distension[Ref]


Common (1% to 10%): Pelvic pain, breast disorder, breast enlargement, breast neoplasm, breast pain, cervix disorder, dysmenorrhea, endometrial disorder, endometrial hyperplasia, leukorrhea, metrorrhagia, urinary tract infection, uterine fibroids enlarged, uterine spasm, abnormal uterine bleeding (breakthrough bleeding/spotting), vaginal dryness, vaginal hemorrhage, vaginal moniliasis, vaginitis

Uncommon (0.1% to 1%): Vaginal candidiasis, changes in menstrual flow, changes in cervical ectropion and secretion

Postmarketing reports: Increases in seize of uterine leiomyomata, change in cervical secretion, ovarian cancer, endometrial cancer, breast tenderness, breast discharge, galactorrhea, fibrocystic breast changes, breast cancer, gynecomastia in males[Ref]


Common (1% to 10%): Hyperlipidemia, weight gain, increased appetite

Very rare (less than 0.01%): Hypocalcemia

Postmarketing reports: Increase or decrease in weight, glucose intolerance, aggravation of porphyria, increased triglycerides[Ref]


Common (1% to 10%): Back pain, arthralgia, leg cramps, myalgia, muscle spasm[Ref]

Nervous system

Common (1% to 10%): Headache, dizziness, paresthesia, migraine, hypertonia, insomnia, nervousness

Very rare (less than 0.01%): Exacerbation of chorea

Postmarketing reports: Exacerbation of epilepsy, dementia[Ref]


Common (1% to 10%): Accidental injury, asthenia, chills, flu syndrome, pain, edema, peripheral edema, generalized edema, moniliasis

Postmarketing reports: Irritability[Ref]


Common (1% to 10%): Depression, emotional liabilities, anxiety

Uncommon (0.1% to 1%): Changes in libido, mood disturbances[Ref]


Common (1% to 10%): Chest pain, bronchitis, increased cough, pharyngitis, rhinitis, sinusitis, upper respiratory tract infection

Postmarketing reports: Exacerbation of asthma[Ref]


Uncommon (0.1% to 1%): Gallbladder disease

Postmarketing reports: Cholestatic jaundice, pancreatitis, enlargement of hepatic hemangiomas, ischemic colitis[Ref]


Uncommon (0.1% to 1%): Hypersensitivity

Rare (less than 0.1%): Anaphylactic/anaphylactoid reactions including urticaria and angioedema[Ref]


Uncommon (0.1% to 1%): Intolerance to contact lenses, steepening of corneal curvature

Postmarketing reports: Retinal vascular thrombosis[Ref]


Rare (0.01% to 0.1%): Breast cancer, ovarian cancer, fibrocystic breast changes, growth potentiation of benign meningioma.

Very rare (less than 0.01%): Endometrial cancer, enlargement of hepatic hemangiomas[Ref]

Breast cancer:

-An up to 2-fold increased risk of having breast cancer diagnosed is reported in women taking combined estrogen-progestin therapy for more than 5 years.

-Any increased risk in users of estrogen-only therapy is substantially lower than that seen in users of estrogen-progestin combinations. The level of risk is dependent on the duration of use.

Endometrial Cancer:

-Endometrial cancer risk is about 5 in every 1000 women with a uterus not using HRT.

-In women with a uterus, use of estrogen-only HRT is not recommended because it increases the risk of endometrial cancer.

-Depending on the duration of estrogen-only use and estrogen dose, the increase in risk of endometrial cancer varied from between 5 and 55 extra cases diagnosed in every 1000 women between the ages of 50 and 65.

-Adding a progestin to estrogen-only therapy for at least 12 days per cycle can prevent this increased risk. In the Million Women Study the use of five years of combined HRT did not increase risk of endometrial cancer.

Ovarian cancer:

-Long-term use of estrogen-only and combined estrogen-progestin HRT has been associated with a slightly increased risk of ovarian cancer. In the Million Women Study 5 years of HRT resulted in 1 extra case per 2500 users.[Ref]


1. Crane MG, Harris JJ (1978) "Estrogens and hypertension: effect of discontinuing estrogens on blood pressure, exchangeable sodium, and the renin-aldosterone system." Am J Med Sci, 276, p. 33-55

2. Crane MG, Harris JJ, Winsor W 3d (1971) "Hypertension, oral contraceptive agents, and conjugated estrogens." Ann Intern Med, 74, p. 13-21

3. Rosenberg L, Slone D, Shapiro S, Kaufman D, Stolley PD, Miettinen OS (1980) "Noncontraceptive estrogens and myocardial infarction in young women." JAMA, 244, p. 339-42

4. Jick H, Dinan B, Rothman KJ (1978) "Noncontraceptive estrogens and nonfatal myocardial infarction." JAMA, 239, p. 1407-8

5. Wren BG, Routledge DA (1981) "Blood pressure changes: oestrogens in climacteric women." Med J Aust, 2, p. 528-31

6. Belchetz PE (1994) "Hormonal treatment of postmenopausal women." N Engl J Med, 330, p. 1062-71

7. Stampfer MJ, Colditz GA, Willett WC, et al. (1991) "Postmenopausal estrogen and cardiovascular disease. Ten-year follow-up from the Nurses' Health Study." N Engl J Med, 325, p. 756-62

8. Barrett-Connor E, Bush TL (1991) "Estrogen and coronary heart disease in women." JAMA, 265, p. 1861-7

9. Grady D, Rubin SM, Petiti DB, et al. (1992) "Hormone therapy to prevent disease and prolong life in postmenopausal women." Ann Intern Med, 117, p. 1016-36

10. Barrett-Connor E, Wingard DL, Criqui MH (1989) "Postmenopausal estrogen use and heart disease risk factors in the 1980s. Rancho Bernardo, Calif, revisited." JAMA, 261, p. 1095-2100

11. (2001) "Product Information. Premarin (conjugated estrogens)." Wyeth-Ayerst Laboratories

12. Schwartz J, Freeman R, Frishman W (1995) "Clinical pharmacology of estrogens: cardiovascular actions and cardioprotective benefits of replacement therapy in postmenopausal women." J Clin Pharmacol, 35, p. 1-16

13. The Writing Group for the PEPI Trial (1995) "Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women: the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial." JAMA, 273, p. 199-208

14. Collins P, Beale CM, Rosano GMC (1996) "Oestrogen as a calcium channel blocker." Eur Heart J, 17 ( Suppl, p. 27-31

15. Sidney S, Petitti DB, Quesenberry CP (1997) "Myocardial infarction and the use of estrogen and estrogen-progestogen in postmenopausal women." Ann Intern Med, 127, p. 501-8

16. Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs B, Vittinghoff E (1998) "Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women." JAMA, 280, p. 605-13

17. Petitti DB (1998) "Hormone replacement therapy and heart disease prevention: experimentation trumps observation." JAMA, 280, p. 650-2

18. Mendelsohn ME, Karas RH (1999) "The protective effects of estrogen on the cardiovascular system." N Engl J Med, 340, p. 1801-11

19. Herrington DM (1999) "The HERS Trial results: paradigms lost?" Ann Intern Med, 131, p. 463-6

20. Pripp U, Hall G, Csemiczky G, Eksborg S, Landgren BM, SchenckGustafsson K (1999) "A randomized trial on effects of hormone therapy on ambulatory blood pressure and lipoprotein levels in women with coronary artery disease." J Hypertens, 17, p. 1379-86

21. Kamali P, Muller T, Lang U, Clapp JF (2000) "Cardiovascular responses of perimenopausal women to hormonal replacement therapy." Am J Obstet Gynecol, 182, p. 17-22

22. Gordeuk VR, Brittenham GM, Hughes M, Keating LJ, Opplt JJ (1987) "High-dose carbonyl iron for iron deficiency anemia: a randomized double-blind trial." Am J Clin Nutr, 46, p. 1029-34

23. Grady D, Wenger NK, Herrington D, et al. (2000) "Postmenopausal hormone therapy increases risk for venous thromboembolic disease: the heart and estrogen replacement study." Ann Intern Med, 132, p. 689-96

24. Herrington DM, Reboussin DM, Brosniham KB, et al. (2000) "Effects of estrogen replacement on the progression of coronary-artery atherosclerosis." N Engl J Med, 343, p. 522-9

25. Lindsay R, Gallagher JC, Kleerekoper M, Pickar JH (2002) "Effect of lower doses of conjugated equine estrogens with and without medroxyprogesterone acetate on bone in early postmenopausal women." JAMA, 287, p. 2668-76

26. Miller J, Chan BK, Nelson HD (2002) "Postmenopausal estrogen replacement and risk for venous thromboembolism: a systematic review and meta-analysis for the U.S. preventive services task force." Ann Intern Med, 136, p. 680-90

27. Cerner Multum, Inc. "UK Summary of Product Characteristics."

28. Cerner Multum, Inc. "Australian Product Information."

29. (2015) "Product Information. Enjuvia (conjugated estrogens)." Barr Pharmaceuticals Inc

30. McClennan BL (1976) "Ischemic colitis secondary to Premarin: report of a case." Dis Colon Rectum, 19, p. 618-20

31. Perusse R, Morency R (1991) "Oral pigmentation induced by Premarin." Cutis, 48, p. 61-4

32. Boston Collaborative Drug Surveilance Program (1974) "Surgically confirmed gallbladder disease, venous thromboembolism, and breast tumors in relation to postmenopausal estrogen therapy." N Engl J Med, 290, p. 15-9

33. OrrWalker BJ, Horne AM, Evans MC, Grey AB, Murray MAF, McNeil AR, Reid IR (1999) "Hormone replacement therapy causes a respiratory alkalosis in normal postmenopausal women." J Clin Endocrinol Metab, 84, p. 1997-2001

34. Gambacciani M, Ciaponi M, Cappagli B, Genazzani AR (2001) "Effects of low-dose continuous combined conjugated estrogens and medroxyprogesterone acetate on menopausal symptoms, body weight, bone density, and metabolism in postmenopausal women." Am J Obstet Gynecol, 185, p. 1180-5

35. Wakatsuki A, Okatani Y, Ikenoue N, Fukaya T (2002) "Different effects of oral conjugated equine estrogen and transdermal estrogen replacement therapy on size and oxidative susceptibility of low-density lipoprotein particles in postmenopausal women." Circulation, 106, p. 1771-6

36. Civitelli R, Pilgram TK, Dotson M, et al. (2002) "Alveolar and Postcranial Bone Density in Postmenopausal Women Receiving Hormone/Estrogen Replacement Therapy: A Randomized, Double-blind, Placebo-Controlled Trial." Arch Intern Med, 162, p. 1409-15

37. Steiger MJ, Quinn NP (1991) "Hormone replacement therapy induced chorea." BMJ, 302, p. 762

38. Jick SS, Walker AM, Jick H (1986) "Conjugated estrogens and fibrocystic breast disease." Am J Epidemiol, 124, p. 746-51

39. Pastides H, Najjar MA, Kelsey JL (1987) "Estrogen replacement therapy and fibrocystic breast disease." Am J Prev Med, 3, p. 282-6

40. Oppenheim G (1984) "A case of rapid mood cycling with estrogen: implications for therapy." J Clin Psychiatry, 45, p. 34-5

41. Conter RL, Longmire WP Jr (1988) "Recurrent hepatic hemangiomas. Possible association with estrogen therapy." Ann Surg, 207, p. 115-9

42. Aldinger K, Ben-Menachem Y, Whalen G (1977) "Focal nodular hyperplasia of the liver associated with high-dosage estrogens." Arch Intern Med, 137, p. 357-9

43. Caucino JA, Armenaka M, Rosenstreich DL (1994) "Anaphylaxis associated with a change in premarin dye formulation." Ann Allergy, 72, p. 33-5

44. Searcy CJ, Kushner M, Nell P, Beckmann CR (1987) "Anaphylactic reaction to intravenous conjugated estrogens." Clin Pharm, 6, p. 74-6

45. Obrink A, Bunne G, Collen J, Tjernberg B (1979) "Endometrial cancer and exogenous estrogens." Acta Obstet Gynecol Scand, 58, p. 123

46. Palmer JR, Rosenberg L, Clarke EA, Miller DR, Shapiro S (1991) "Breast cancer risk after estrogen replacement therapy: results from the Toronto Breast Cancer Study." Am J Epidemiol, 134, p. 1386-95

47. Kaufman DW, Palmer JR, de Mouzon J, Rosenberg L, Stolley PD, Warshauer ME, Zauber AG, Shapiro S (1991) "Estrogen replacement therapy and the risk of breast cancer: results from the case-control surveillance study." Am J Epidemiol, 134, p. 1375-85

48. Spengler RF, Clarke EA, Woolever CA, Newman AM, Osborn RW (1981) "Exogenous estrogens and endometrial cancer: a case-control study and assessment of potential biases." Am J Epidemiol, 114, p. 497-506

49. Buring JE, Bain CJ, Ehrmann RL (1986) "Conjugated estrogen use and risk of endometrial cancer." Am J Epidemiol, 124, p. 434-41

50. Persson I, Adami HO, Bergkvist L, Lindgren A, Pettersson B, Hoover R, Schairer C (1989) "Risk of endometrial cancer after treatment with oestrogens alone or in conjunction with progestogens: results of a prospective study." BMJ, 298, p. 147-51

51. Hoover R, Glass A, Finkle WD, Azevedo D, Milne K (1981) "Conjugated estrogens and breast cancer risk in women." J Natl Cancer Inst, 67, p. 815-20

52. Thomas DB, Persing JP, Hutchinson WB (1982) "Exogenous estrogens and other risk factors for breast cancer in women with benign breast diseases." J Natl Cancer Inst, 69, p. 1017-25

53. Antunes CM, Strolley PD, Rosenshein NB, Davies JL, Tonascia JA, Brown C, Burnett L, Rutledge A, Pokempner M, Garcia R (1979) "Endometrial cancer and estrogen use. Report of a large case-control study." N Engl J Med, 300, p. 9-13

54. Gordon J, Reagan JW, Finkle WD, Ziel HK (1977) "Estrogen and endometrial carcinoma. An independent pathology review supporting original risk estimate." N Engl J Med, 297, p. 570-1

55. Bergkvist L, Adami HO, Persson I, Hoover R, Schairer C (1989) "The risk of breast cancer after estrogen and estrogen-progestin replacement." N Engl J Med, 321, p. 293-7

56. Shapiro S, Kelly JP, Rosenberg L, Kaufman DW, Helmrich SP, Rosenshein NB, Lewis JL Jr, Knapp RC, Stolley PD, Schottenfeld D (1985) "Risk of localized and widespread endometrial cancer in relation to recent and discontinued use of conjugated estrogens." N Engl J Med, 313, p. 969-72

57. Gray LA Sr, Christopherson WM, Hoover RN (1977) "Estrogens and endometrial carcinoma." Obstet Gynecol, 49, p. 385-9

58. Woodruff JD, Pickar JH (1994) "Incidence of endometrial hyperplasia in postmenopausal women taking conjugated estrogens (Premarin) with medroxyprogesterone acetate or conjugated estrogens alone." Am J Obstet Gynecol, 170, p. 1213-23

59. Colditz GA, Hankinson SE, Hunter DJ, et al. (1995) "The use of estrogens and progestins and the risk of breast cancer in postmenopausal women." N Engl J Med, 332, p. 1589-93

60. Stanford JL, Weiss NS, Voigt LF, Daling JR, Habel LA, Rossing MA (1995) "Combined estrogen and progestin hormone replacement therapy in relation to risk of breast cancer in middle-aged women." JAMA, 274, p. 137-42

61. The Writing Group for the PEPI Trial (1996) "Effects of hormone replacement therapy on endometrial histology in postmenopausal women." JAMA, 275, p. 370-5

62. Greendale GA, Reboussin BA, Sie A, et al. (1999) "Effects of estrogen and estrogen-progestin on mammographic parenchymal density." Ann Intern Med, 130, p. 262-9

63. Gapstur SM, Morrow M, Sellers TA (1999) "Hormone replacement therapy and risk of breast cancer with a favorable histology: results of the Iowa women's health study." JAMA, 281, p. 2091-7

64. Ziel HK, Finkle WD (1975) "Increased risk of endometrial carcinoma among users of conjugated estrogens." N Engl J Med, 293, p. 1167-70

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.