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Androgen Excess Medication

  • Author: Mohamed Yahya Abdel-Rahman, MD, MSc; Chief Editor: Richard Scott Lucidi, MD, FACOG  more...
 
Updated: Jul 26, 2015
 

Medication Summary

Medical treatment of androgen excess is aimed at lowering ovarian or adrenal androgen production, reducing the free androgen level, and blocking the peripheral androgen action. However, patients with androgen excess typically seek medical attention for the treatment of primary symptoms, such as hirsutism, acne, and menstrual disorders.

Hirsutism is best treated by a combination of mechanical and chemical methods. The mechanical methods remove hair immediately, and the chemical methods prevent further differentiation of vellus to terminal hairs.

PCOS associated with insulin resistance can be treated with metformin and/or an OC with or without an added antiandrogen (spironolactone). PCOS not associated with insulin resistance is best treated with an OC with or without added spironolactone.

Acne treatment is aimed at decreasing skin sloughing and proliferation of P acnes through the use of topical and systemic agents. Suppression of androgen production decreases production of sebum and reduces acne.

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Oral contraceptives

Class Summary

Oral contraceptives (OCs) decrease ovarian androgen production and increase SHBG, therefore reducing free testosterone by approximately 50%. OCs also decrease adrenal androgen production, particularly DHEAS. The reduction in ovarian androgens is in relation to the OCs capacity to inhibit ovulation. Low-strength preparations (20 µg ethinyl estradiol) are less efficient than standard or high-strength preparations in inhibiting ovulation. The presence of less androgenic progestin (desogestrel, norgestimate) in third-generation OCs is not associated with better outcome compared with older OCs. By promoting regular bleeding, OCs reduce the incidence of endometrial hyperplasia and cancer.

OCs alone or in combination with antiandrogens are the first choice for the treatment of hirsutism in women needing contraception. All strengths of OC pills have been shown to improve acne. The choice of an OC should be based solely on personal preference of the health care provider and patient. The new OC containing the antiandrogens drospirenone and ethinyl estradiol (Yasmin) has not shown advantages over other preparations.

Ethinyl estradiol

 

Ethinyl estradiol reduces the secretion of LH and FSH from the pituitary by decreasing the amount of GnRH. Use ethinyl estradiol 30-35 mg combined with any form of progesterone. Improvements of hyperandrogenic effects are seen in 60-100% of women but usually require a least 6-12 months of use. Perform a pregnancy test before therapy. If the patient has had no menstrual period for 3 months, induce withdrawal bleeding with medroxyprogesterone acetate (Provera) 5-10 mg/day for 10 days, then begin therapy with oral contraceptives.

Drospirenone and ethinyl estradiol (Yasmin)

 

Combination of estrogen and progestin treats hirsutism in adult women. Suppresses ovarian production of androgens.

Ethinyl Estradiol, drospirenone, and levomefolate (Beyaz)

 

Combination of estrogen and progestin treats hirsutism in adult women. Suppresses ovarian production of androgens.

Ethinyl estradiol and norethindrone (Estrostep Fe)

 

Combination of estrogen and progestin treats hirsutism in adult women. Suppresses ovarian production of androgens.

Ethinyl estradiol and norgestimate (Ortho Tri-Cyclen)

 

Combination of estrogen and progestin treats hirsutism in adult women. Suppresses ovarian production of androgens.

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Antiandrogens

Class Summary

Antiandrogens are another group of agents used as a first-line therapy for hirsutism. However, the teratogenic potential of these drugs means that they should be used in conjunction with adequate contraception in women of reproductive age. Spironolactone, an aldosterone antagonist, competes with testosterone and dihydrotestosterone at the androgen receptor. Although its primary indication is as a diuretic, a dose of 50-200 mg/d will reduce facial hair growth in most patients after 6 cycles of treatment.[74] Concurrent use of spironolactone with OC pills has been shown to significantly improve hirsutism and reduce serum androgen levels.[75] For patients with hirsutism that is refractory to OCs after 6 months, adding spironolactone may be effective.

Flutamide is an antiandrogen used for the treatment of prostate cancer. It is more effective in treating hirsutism than spironolactone.[76] However, a recent study concluded that although flutamide is very effective in treating hirsutism, it is associated with frequent side effects and low long-term compliance.[77] Hepatic cell damage, the major complication of flutamide, may be fatal.[78] Consequently, flutamide is not approved by the FDA for treatment of hirsutism.

Cyproterone acetate is an antiandrogen as well as a progestin. In one systematic review, cyproterone acetate (2 mg) was more effective than placebo, but not better than any other antiandrogen in the treatment of hirsutism.[77] It is also available in an OC pill as cyproterone acetate (2 mg) with 35 u ethinyl estradiol, which has been shown to be well tolerated. This drug is not currently available in the United States.

Finasteride, another antiandrogen, inhibits only the type 2 isoenzyme of 5 α-reductase. It is anticipated that the effect of finasteride may be partial. Whether it is equally effective or less effective than spironolactone is controversial.[79, 80] The FDA has not approved finasteride for treatment of hirsutism.

Spironolactone (Aldactone)

 

Used most effectively in combination with an OC. First choice because of few adverse effects, cost, and clinical experience.

Flutamide (Eulexin)

 

Nonsteroidal antiandrogen that inhibits androgen uptake or binding of androgen to target tissues.

Cyproterone acetate

 

Powerful antiandrogen usually administered with estrogens to maintain regular menstruation and to prevent conception. Not available in United States.

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Aldosterone Antagonists, Selective

Class Summary

Aldosterone antagonists may reduce free testosterone levels and compete with androgens binding at receptor sites.

Spironolactone (Aldactone)

 

Aldosterone antagonist that competes with testosterone and dihydrotestosterone receptor sites. It also reduces free testosterone levels as more is bound by the increased quantity of SHBG. Used most effectively in combination with an OC.

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5-Alpha-Reductase Inhibitors

Class Summary

Agents in this class can markedly suppress serum dihydrotestosterone (DHT) levels.

Finasteride (Proscar, Propecia)

 

Predominantly a type 2, 5α-reductase inhibitor. Inhibits the production of DHT. Efficacy in hirsutism is similar to that of spironolactone.

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Gonadotropin Releasing Hormone Antagonists

Class Summary

These agents, which suppress pituitary LH and FSH secretion, suppress ovarian hormone secretion to a greater degree than COCs. Examples of GnRH agonists in the United States include Lupron, Synarel, and Zoladex. The endometriosis doses are the ones used for hirsutism. Significant osteoporosis may occur if treatment lasts longer than 6 months; in these cases, estrogen add back with HRT or COC pills should be given.

Leuprolide acetate (Lupron, Lupron Depot)

 

Suppresses ovarian and testicular steroidogenesis by decreasing LH and FSH levels.

Nafarelin acetate (Synarel)

 

Suppresses secretion of LH and FSH, which in turn reduces ovarian and testicular steroid production. Available as nasal solution (2 mg/mL).

Goserelin (Zoladex)

 

Suppresses ovarian and testicular steroidogenesis by decreasing LH and FSH levels.

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Corticosteroids

Class Summary

Adrenal hyperandrogenism responds well to low-dose glucocorticoid therapy with dexamethasone or prednisolone. These agents are used with variable success in women with adrenal hirsutism, CAH, and idiopathic adrenal hyperandrogenism. Glucocorticoids have anti-inflammatory properties and cause profound and varied metabolic effects. Changes suggesting Cushing disease may develop in patients receiving long-term therapy.

Dexamethasone (Baycadron)

 

May reduce steroid hormone production. Decreases immune reactions.

Prednisone

 

May reduce steroid hormone production. Decreases immune reactions.

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Insulin-sensitizing drugs

Class Summary

Hyperinsulinemia has been shown to increase ovarian androgen production[81] and decrease SHBG production[82] . Consequently, reducing insulin levels with insulin-sensitizing agents such as metformin should lower total and free androgen levels. However, the effects on hirsutism are not clearly better than if OCs are used; some studies have shown insulin-sensitizing agents to improve hirsutism and others have not.[83, 84, 85, 86] One systematic review and one meta-analysis of 8 trials collectively found no significant difference in hirsutism scores between COCs and metformin.[87, 88] On the other hand, antiandrogen drugs (spironolactone, cyproterone acetate, and flutamide) have been found to significantly reduce hirsutism scores when compared to metformin in a recent meta-analysis.[88]

Metformin (Glucophage, Riomet, Fortamet, Glumetza)

 

Reduces hepatic glucose output, decreases intestinal absorption of glucose, and increases glucose uptake in the peripheral tissues (muscle and adipocytes). Major drug used in patients who are obese and have type 2 diabetes. Effective in inducing ovulation in PCOS anovulatory women.

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Topical skin products

Class Summary

May be used to reduce hair growth on the face and adjacent areas under the chin.

Eflornithine 13.9% cream (Vaniqa)

 

Prescription topical cream that acts as a growth inhibitor of hair. Takes up to 2 mo to work in approximately 30% of patients. Apply to skin bid at least 8 h apart, and area of application should not be washed for at least 4 h

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Antiparkinson Agents, Dopamine agonists

Class Summary

Women with hyperandrogenism who also have hyperprolactinemia may benefit from therapy with a dopamine receptor agonist (bromocriptine, cabergoline). These agents improve menstrual cycle, ovulation, and hirsutism in women with PCOS and hyperprolactinemia.

Bromocriptine (Parlodel, Cycloset)

 

Semisynthetic ergot alkaloid derivative; strong dopamine D2-receptor agonist; partial dopamine D1-receptor agonist. Inhibits prolactin secretion with no effect on other pituitary hormones. May be given with food to minimize possibility of GI irritation.

Cabergoline

 

Semisynthetic ergot alkaloid derivative; strong dopamine D2-receptor agonist with low affinity for D1 receptors.

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Contributor Information and Disclosures
Author

Mohamed Yahya Abdel-Rahman, MD, MSc Research Fellow, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University Hospitals, Case Western Reserve University School of Medicine; Assistant Lecturer, Sohag University School of Medicine, Egypt

Mohamed Yahya Abdel-Rahman, MD, MSc is a member of the following medical societies: American Institute of Ultrasound in Medicine, American Society for Reproductive Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

William W Hurd, MD, MSc, MPH Professor and Director, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Duke University Medical Center

William W Hurd, MD, MSc, MPH is a member of the following medical societies: American College of Surgeons, American Gynecological and Obstetrical Society, AAGL, Society of Reproductive Surgeons, Alpha Omega Alpha, American College of Obstetricians and Gynecologists, American Medical Association, American Society for Reproductive Medicine, Society for Reproductive Investigation

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Steven R Feldman, MD, PhD Professor, Departments of Dermatology, Pathology and Public Health Sciences, and Molecular Medicine and Translational Science, Wake Forest Baptist Health; Director, Center for Dermatology Research, Director of Industry Relations, Department of Dermatology, Wake Forest University School of Medicine

Steven R Feldman, MD, PhD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, North Carolina Medical Society, Society for Investigative Dermatology

Disclosure: Received honoraria from Amgen for consulting; Received honoraria from Abbvie for consulting; Received honoraria from Galderma for speaking and teaching; Received consulting fee from Lilly for consulting; Received ownership interest from www.DrScore.com for management position; Received ownership interest from Causa Reseasrch for management position; Received grant/research funds from Janssen for consulting; Received honoraria from Pfizer for speaking and teaching; Received consulting fee from No.

Chief Editor

Richard Scott Lucidi, MD, FACOG Associate Professor of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Virginia Commonwealth University School of Medicine

Richard Scott Lucidi, MD, FACOG is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Society for Reproductive Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Arash Taheri, MD Research Fellow, Center for Dermatology Research, Department of Dermatology, Wake Forest University School of Medicine

Disclosure: Nothing to disclose.

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Androgen secretion pathway in adrenal glands and ovaries.
Chemical structures of spironolactone and drospirenone. The testosterone core is in black.
Table. Ferriman-Gallwey Scoring System
Body Area Evaluated Score



(Graded from 0-4*)



Upper lip  
Chin  
Upper abdomen  
Lower abdomen  
Upper arm  
Thighs  
Upper back  
Lower back/buttocks  
*0 = No hirsutism, 4 = Severe hirsutism
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