Androgen Excess Medication
- Author: Mohamed Yahya Abdel-Rahman, MD, MSc; Chief Editor: Richard Scott Lucidi, MD more...
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.
Combined 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.
Combined oral contraceptives
Any combination COC can be prescribed. No preparation has any advantage over the others.
Drospirenone and ethinyl estradiol (Yasmin)
Drospirenone 3 mg and ethinyl estradiol 30 µg
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.[79] Concurrent use of spironolactone with OC pills has been shown to significantly improve hirsutism and reduce serum androgen levels.[80] 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.[81] 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.[82] Hepatic cell damage, the major complication of flutamide, may be fatal.[83] 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.[82] 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.[84, 85] 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 (Androcur, Diane-35, Diane-50)
Available in combination with ethinyl estradiol:
Diane-35, 2 mg cyproterone acetate and 35 µg ethinyl estradiol, reverse sequential.
Diane-50, 2 mg cyproterone acetate and 50 µg ethinyl estradiol, reverse sequential.
Powerful antiandrogen usually administered with estrogens to maintain regular menstruation and to prevent conception. Not available in United States.
Finasteride (Proscar, Propecia)
Predominantly a type 2, 5 α -reductase inhibitor. Inhibits the production of DHT. Efficacy in hirsutism is similar to that of spironolactone.
GnRH agonists/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.
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 (Decadron, AK-Dex, Alba-Dex, Baldex, Dexone, Dexasone)
May reduce steroid hormone production. Decreases immune reactions.
Prednisone (Sterapred)
May reduce steroid hormone production. Decreases immune reactions.
Insulin-sensitizing drugs
Class Summary
Hyperinsulinemia has been shown to increase ovarian androgen production[86] and decrease SHBG production[87] . 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.[88, 89, 90, 91] One systematic review and one meta-analysis of 8 trials collectively found no significant difference in hirsutism scores between COCs and metformin.[92, 93] 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.[93]
Metformin (Glucophage)
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.
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.
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)
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 (Dostinex)
Semisynthetic ergot alkaloid derivative; strong dopamine D2-receptor agonist with low affinity for D1 receptors.
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| 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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