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Depo-Estradiol Side Effects

Generic Name: estradiol

Medically reviewed on June 7, 2018

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ConsumerProfessional Managing Side Effects

Note: This document contains side effect information about estradiol. Some of the dosage forms listed on this page may not apply to the brand name Depo-Estradiol.

For the Consumer

Applies to estradiol: vaginal cream, vaginal insert extended release, vaginal tablet

Other dosage forms:

Along with its needed effects, estradiol (the active ingredient contained in Depo-Estradiol) 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 estradiol:

Less Common

Incidence Not Known

  • Change in vaginal discharge
  • clear or bloody discharge from the nipple
  • decrease in the amount of urine
  • dimpling of the breast skin
  • fast heartbeat
  • fever
  • hives, itching, or rash
  • hoarseness
  • inverted nipple
  • irritation
  • joint pain, stiffness, or swelling
  • 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 of the skin
  • redness or swelling of the breast
  • sore on the skin of the breast that does not heal
  • swelling of the eyelids, face, fingers, lips, hands, feet, or lower legs
  • tightness in the chest
  • troubled breathing at rest
  • troubled breathing or swallowing
  • vaginal bleeding

Get emergency help immediately if any of the following symptoms of overdose occur while taking estradiol:

Symptoms of Overdose

Some side effects of estradiol 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

  • Back pain
  • headache
  • itching or pain of the vagina or genital area
  • thick, white vaginal discharge with mild or no odor
  • weight gain

Less Common

Incidence Not Known

  • Feeling sad or empty
  • headache, severe and throbbing
  • irritability
  • lack of appetite
  • tiredness
  • trouble concentrating
  • trouble sleeping
  • welts

For Healthcare Professionals

Applies to estradiol: compounding powder, intramuscular solution, oral tablet, transdermal emulsion, transdermal film extended release, transdermal gel, transdermal spray, vaginal ring

Genitourinary

Very common (10% or more): Breast pain (29%)

Common (1% to 10%): Vulvovaginal pruritus, leukorrhea, vaginal hemorrhage, vaginal discharge, vaginal discomfort, menopause symptoms, breakthrough bleeding or spotting, dysmenorrhea, breast swelling, menorrhagia, metrorrhagia, endometrial hyperplasia

Uncommon (0.1% to 1%): Urinary problems

Rare (less than 0.1%): Galactorrhea

Postmarketing reports: Vaginal irritation, vaginal pain, genital pruritus, changes in bleeding pattern, pelvic pain, breast tenderness, vaginal ulceration, uterine fibroids[Ref]

Gastrointestinal

Very common (10% or more): Abdominal pain (16%),

Common (1% to 10%): Flatulence, nausea, diarrhea

Uncommon (0.1% to 1%): Vomiting

Postmarketing reports: Abdominal distension[Ref]

Musculoskeletal

Very common (10% or more): Back pain (11%), arthralgia (11%)

Common (1% to 10%): Leg cramps[Ref]

Cardiovascular

Common (1% to 10%): Varicose veins, cardiac symptoms (e.g. palpitations)

Uncommon (0.1% to 1%): Hot flush, hypertension, venous thromboembolic disease

Rare (less than 0.1%): Arterial hypertension

Postmarketing reports: Deep vein thrombosis, changes in blood pressure[Ref]

Nervous system

Very common (10% or more): Headache (18%)

Uncommon (0.1% to 1%): Vertigo, migraine

Rare (less than 0.1%): Aggravation of epilepsy

Postmarketing reports: Migraine aggravated, paresthesia, dizziness[Ref]

Oncologic

Uncommon (0.1% to 1%): Benign breast neoplasm, increased volume of uterine leiomyoma

Postmarketing reports: Endometrial cancer, breast cancer[Ref]

Other

Very common (10% or more): Pain (11%)

Common (1% to 10%): Edema

Uncommon (0.1% to 1%): Weight increased, asthenia

Postmarketing reports: Drug ineffectiveness, blood estrogen increase, fatigue, exacerbation of hereditary angioedema[Ref]

Psychiatric

Common (1% to 10%): Depression

Uncommon (0.1% to 1%): Sleep disorders, nervousness, mood swings

Rare (less than 0.1%): Change in libido

Postmarketing reports: Vaginismus, insomnia, anxiety, irritability[Ref]

Dermatologic

Common (1% to 10%): Pruritus

Uncommon (0.1% to 1%): Rash

Rare (less than 0.1%): Skin discoloration, acne

Postmarketing reports: Urticaria, erythematous or pruritic rash, alopecia, hyperhidrosis, night sweats, contact dermatitis, eczema[Ref]

Ocular

Uncommon (0.1% to 1%): Vision abnormal NOS

Postmarketing reports: Visual disturbances, contact lens intolerance[Ref]

Hepatic

Rare (less than 0.1%): Liver function tests abnormalities

Postmarketing reports: Cholestatic jaundice[Ref]

Metabolic

Rare (less than 0.1%): Glucose intolerance

Postmarketing reports: Fluid retention[Ref]

Hypersensitivity

Rare (less than 0.1%): Anaphylactic reaction (with a past history of allergic reaction)

Postmarketing reports: Anaphylactic reactions, hypersensitivity[Ref]

Immunologic

Very common (10% or more): Upper respiratory tract infection (17%)

Common (1% to 10%): Vulvovaginal mycotic infection, pharyngitis, rhinitis, sinusitis, moniliasis genital

Uncommon (0.1% to 1%): Vaginitis/vaginal candidosis[Ref]

Local

Common (1% to 10%): Skin irritation (topical gel)

Postmarketing reports: Application site reaction[Ref]

References

1. "Product Information. Estradiol Vaginal Insert (estradiol topical)." Teva Pharmaceuticals USA, North Wales, PA.

2. Auerbach R, Mittal K, Schwartz PE "Estrogen and progestin receptors in an ovarian ependymoma." Obstet Gynecol 71 (1988): 1043-5

3. "Product Information. Yuvafem (estradiol topical)." AvKare Inc, Pulaski, TN.

4. Nash HA, AlvarezSanchez F, Mishell DR, Fraser IS, Maruo T, Harmon TM "Estradiol-delivering vaginal rings for hormone replacement therapy." Am J Obstet Gynecol 181 (1999): 1400-6

5. "Product Information. Estrace (estradiol)." Warner Chilcott Laboratories, Rockaway, NJ.

6. Julian TM "Pseudoincontinence secondary to unopposed estrogen replacement in the surgically castrate premenopausal female." Obstet Gynecol 70 (1987): 382-3

7. "Product Information. Climara (estradiol)." Berlex, Richmond, CA.

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

9. 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

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

13. 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

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

15. 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

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17. 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

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

19. 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

20. 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

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22. Bui MN, Arai AE, Hathaway L, Waclawiw MA, Csako G, Cannon RO 3rd "Effect of hormone replacement therapy on carotid arterial compliance in healthy postmenopausal women." Am J Cardiol 90 (2002): 82-5

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

24. Cohen L, Coxwell WL, Melchione T, Koltun W, Gibson E, Gupta N, Roberts M "Low-dose 17-beta estradiol matrix transdermal system in the treatment of moderate-to-severe hot flushes in postmenopausal women." Curr Ther Res Clin Exp 60 (1999): 534-47

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

26. 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

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28. 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

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

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

31. 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

32. 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

33. 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

34. 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

35. 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

36. 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

37. 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

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

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

40. 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

41. Molitch ME, Oill P, Odell WD "Massive hyperlipemia during estrogen therapy." JAMA 227 (1974): 522-5

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.

Medical Disclaimer

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