Skip to Content

Cenestin Side Effects

Generic Name: conjugated estrogens

Note: This page contains information about the side effects of conjugated estrogens. Some of the dosage forms included on this document may not apply to the brand name Cenestin.

Not all side effects for Cenestin may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

For the Consumer

Applies to conjugated estrogens: oral tablet

In addition to its needed effects, some unwanted effects may be caused by conjugated estrogens (the active ingredient contained in Cenestin). In the event that any of these side effects do occur, they may require medical attention.

You should check with your doctor immediately if any of these side effects occur when taking conjugated estrogens:

More common
  • Bloating or swelling of the face, arms, hands, lower legs, or feet
  • cough
  • cramps
  • difficulty with swallowing
  • dizziness
  • fast heartbeat
  • heavy bleeding
  • hives, itching, or skin rash
  • itching of the vagina or genital area
  • normal menstrual bleeding occurring earlier, possibly lasting longer than expected
  • pain during sexual intercourse
  • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
  • rapid weight gain
  • thick, white vaginal discharge with no odor or with a mild odor
  • tightness in the chest
  • tingling of the hands or feet
  • unusual tiredness or weakness
  • unusual weight gain or loss
Incidence not known
  • Acid or sour stomach
  • backache
  • belching
  • change in vaginal discharge
  • clear or bloody discharge from the nipple
  • confusion
  • decrease in the amount of urine
  • difficulty with speaking
  • dimpling of the breast skin
  • double vision
  • headache
  • heartburn
  • inability to move the arms, legs, or facial muscles
  • inability to speak
  • indigestion
  • inverted nipple
  • loss of appetite
  • lump in the breast or under the arm
  • noisy, rattling breathing
  • pain or feeling of pressure in the pelvis
  • pain, redness, or swelling in the arm or leg
  • persistent crusting or scaling of the nipple
  • redness or swelling of the breast
  • slow speech
  • sore on the skin of the breast that does not heal
  • stomach discomfort, upset, or pain
  • swelling of the abdominal or stomach area
  • swelling of the fingers, hands, feet, or lower legs
  • troubled breathing at rest
  • vaginal bleeding

Some of the side effects that can occur with conjugated estrogens may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

More common
  • Burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
  • excess air or gas in the stomach or intestines
  • fear or nervousness
  • heartburn
  • increased clear or white vaginal discharge
  • indigestion
  • lack or loss of strength
  • loss of bladder control
  • nausea
  • passing gas
  • runny nose
  • sneezing
  • stuffy nose
  • vomiting
Less common
  • Back pain
  • increased appetite
Incidence not known
  • Breast pain, swelling, or tenderness
  • discouragement
  • enlarged breasts
  • feeling sad or empty
  • hair loss or thinning of the hair
  • irritability
  • lack of appetite
  • loss of interest or pleasure
  • sleepiness or unusual drowsiness
  • tiredness
  • trouble concentrating
  • trouble sleeping

For Healthcare Professionals

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


-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%): Hypertension, palpitation, vasodilation
Rare (less than 0.1%): Stroke
Postmarketing reports: Deep and superficial venous thrombosis, pulmonary embolism, thrombophlebitis, myocardial infarction, stroke[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. 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

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

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

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

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

6. 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

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

8. 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

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

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

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

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

13. 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

14. 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

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

16. 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

17. "Product Information. Premarin (conjugated estrogens)." Wyeth-Ayerst Laboratories, Philadelphia, PA.

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

19. 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

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

21. Cerner Multum, Inc. "Australian Product Information." O 0

22. "Product Information. Enjuvia (conjugated estrogens)." Barr Pharmaceuticals Inc, Pomona, NY.

23. Miller J, Chan BK, Nelson HD "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 (2002): 680-90

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

25. 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

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

27. 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

28. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0

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

30. 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

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

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

33. Wakatsuki A, Okatani Y, Ikenoue N, Fukaya T "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 (2002): 1771-6

34. Gambacciani M, Ciaponi M, Cappagli B, Genazzani AR "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 (2001): 1180-5

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

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

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

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

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

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

41. 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

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

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

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

45. 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

46. 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

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

48. 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

49. 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

50. 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

51. 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

52. 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

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

54. 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

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

56. 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

57. 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

58. 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

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

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

61. 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

62. 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

63. 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

64. 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

Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This material does not endorse drugs, diagnose patients, or recommend therapy. This information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate safety, effectiveness, or appropriateness for any given patient. does not assume any responsibility for any aspect of healthcare administered with the aid of materials provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the substances you are taking, check with your doctor, nurse, or pharmacist.