Polycystic Ovarian Syndrome Medication

Updated: Sep 19, 2019
  • Author: Richard Scott Lucidi, MD, FACOG; Chief Editor: Richard Scott Lucidi, MD, FACOG  more...
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Medication Summary

Drugs used in the treatment of polycystic ovarian syndrome (PCOS) include metformin (off-label use), spironolactone, eflornithine (topical cream to treat hirsutism), and oral contraceptives. Oral contraceptives containing a combination of estrogen and progestin increase sex hormone–binding globulin (SHBG) levels and thereby reduce the free testosterone level. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels are also suppressed. This restores cyclic exposure of the endometrium to estrogen-progestin, with the resumption of menstrual periods and decreased hirsutism. However, the use of oral contraceptives may be associated with an increased risk of thrombosis and metabolic abnormalities.

An oral contraceptive containing ethinyl estradiol and a progestin with minimal androgenic activity, such as norgestimate, norethindrone, or desogestrel, should be selected. Ethinyl estradiol combined with drospirenone (Yasmin) has a progestin that acts as an antiandrogen and thus may add antiandrogenic effects.

Withdrawal bleeding can be induced with medroxyprogesterone (Provera) given for 5-10 days before the start of oral contraceptive therapy. Pregnancy must be ruled out before oral contraceptive therapy is started.

The indications, contraindications, and adverse effects of metformin therapy should be carefully reviewed with the patient before such therapy is begun. In addition, women starting metformin therapy should be informed that such treatment may result in ovulatory menstrual cycles and increase the probability of pregnancy. It is worth noting that metformin has the potential to reduce preeclampsia and gestational diabetes in pregnant women with PCOS. [64]

Women taking spironolactone require reliable contraception. An oral contraceptive is preferable, but if that form of contraception is contraindicated, another type of contraception should be used.

FDA safety alerts


On March 1, 2012, the US Food and Drug Administration (FDA) notified health care professionals of updates to the prescribing information concerning interactions between protease inhibitors (drugs for management of human immunodeficiency virus [HIV] and hepatitis B infection) and certain statin drugs. Protease inhibitors and statins taken together may raise the blood levels of statins and increase the risk for muscle injury (myopathy). The most serious form of myopathy, called rhabdomyolysis, can damage the kidneys and lead to kidney failure, which can be fatal.

On February 28, 2012, the FDA approved important safety label changes for the class of cholesterol-lowering drugs known as statins. The changes include removal of routine monitoring of liver enzymes from drug labels. Information about the potential for generally non-serious and reversible cognitive side effects and reports of increased blood glucose and glycosylated hemoglobin (HbA1c) levels has been added to the statin labels. The lovastatin label has been extensively updated with new contraindications and dose limitations when it is taken with certain medicines that can increase the risk for muscle injury.

On June 8, 2011, the FDA notified health care professionals that it recommended limiting the use of the highest approved dose of the cholesterol-lowering medication simvastatin (80 mg) because of increased risk of muscle damage. The FDA required changes to the simvastatin label to add new contraindications (should not be used with certain medications) and dose limitations for using simvastatin with certain medicines.


On October 8, 2010, Abbott Laboratories and the FDA notified health care professionals and patients about the voluntary withdrawal of sibutramine (Meridia), an obesity drug, from the US market because of clinical trial data indicating an increased risk of heart attack and stroke.


Hypoglycemic Agents

Class Summary

These agents reduce blood glucose levels.

Metformin (Glucophage, Glumetza, Riomet, Fortamet)

Metformin reduces insulin resistance; it is an insulin sensitizer. Hepatic glucose output is decreased and peripheral, insulin-stimulated uptake is increased. Metformin may also decrease TSH levels in hypothyroidism patients with polycystic ovarian syndrome (PCOS), regardless of whether they are treated with thyroxine or not (off-label use).

Insulin isophane human/insulin regular human (Humulin 70/30, Novolin 70/30)

Insulin is effective when metformin cannot control hyperglycemia. Several short-acting and long-acting dosage forms are available. Insulin must be initiated in conjunction with dietary assessment and nutritional management by a registered clinical dietitian as part of an overall weight-management system. Insulin is seldom indicated as a first-line agent for PCOS, unless a patient also has a diagnosis of diabetes.



Class Summary

Antiandrogen agents block androgen receptors, thereby inhibiting the effects of male sex hormones. These agents may be used to treat hirsutism in women with PCOS.

Spironolactone (Aldactone)

Spironolactone is an antiandrogen agent that is a nonspecific androgen-receptor blocker. It may be used in conjunction with oral contraceptive pills to treat hirsutism by reducing hair diameter. Initiate oral contraceptive pills first to avoid worsening of menstrual irregularities and to prevent pregnancy, because spironolactone may have feminizing effects on the male fetus. Periodically assess adverse effects (eg, fluid and electrolyte abnormalities). Spironolactone is also used as a potassium-sparing diuretic.

Leuprolide (Lupron, Eligard)

Leuprolide is not a first-line agent in PCOS and therefore is not used often for this syndrome. This agent suppresses ovarian and testicular steroidogenesis by decreasing luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. Gonadotropin-releasing hormone (GnRH) analogs with oral contraceptive pills are an option to consider for hirsutism in women who fail to respond to combined therapy with spironolactone and oral contraceptive pills. Anatomic effects of androgens (eg, clitoromegaly and deepening of the voice) are not responsive to GnRH analogs.

Finasteride (Proscar, Propecia)

Finasteride is a 5-alpha-reductase inhibitor that is approved for use in benign prostatic hypertrophy and in male-pattern alopecia. This agent blocks conversion of testosterone to its more active metabolite, dihydrotestosterone. Finasteride tends to be a second-line agent for hirsutism in PCOS, when hirsutism persists despite the use of first-line agents (ie, oral contraceptives). This agent is more effective when used in combination with oral contraceptive pills. Due to the potential for teratogenic effects (eg, risk of genital ambiguity in male fetuses), finasteride therapy must be used in conjunction with a reliable form of contraception in sexually active women.


Topical Hair-Removal Agents

Class Summary

Eflornithine cream can be used to treat androgen excess.

Eflornithine (Veniqa)

Eflornithine is indicated for the reduction of unwanted facial hair in women. It interferes with ornithine decarboxylase (needed for hair growth) in skin hair follicles. Eflornithine does not have a depilatory action; instead, it appears to retard hair growth and improve appearance where applied. Improvement may be seen in as short a period as 4-8 weeks, although 6 months of treatment may be required. Keep in mind that in clinical studies, hair returned to its previous condition 8 weeks after discontinuation of eflornithine (ie, hirsutism may return following discontinuation of eflornithine).

Note: The use of eflornithine has been studied only on the face and adjacent involved areas under the chin of individuals with hypertrichosis; therefore, limit use of this drug to these areas. Patients will likely need other hair-removal methods in conjunction with eflornithine therapy.


Oral Contraceptives

Class Summary

Oral contraceptive agents reduce the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary gland by decreasing the amount of gonadotropin-releasing hormone (GnRH). All oral contraceptives decrease ovarian androgen production. By inhibiting gonadotropin secretion and, therefore, tertiary follicle development, ovarian secretion of testosterone and androstenedione is decreased. All oral contraceptives increase sex hormone-binding globulin (SHBG) and, therefore, reduce free testosterone. Evidence indicates that high doses of contraceptive progestins may inhibit 5-alpha reductase. Oral contraceptives also decrease the production of adrenal androgens, particularly dehydroepiandrosterone sulfate (DHEA-S).

Different contraceptive preparations have different effects on ovarian androgen production and SHBG. However, they all reduce levels of free testosterone equally (by approximately 50%). Free testosterone levels achieved with oral contraceptive preparations are unrelated to the increased levels of SHBG. Preparations that result in higher SHBG levels also result in higher total testosterone levels. That is, a decrease in free testosterone level is the same for all oral contraceptives and, although some of these preparations increase SHBG levels more than others, this is off-set by a concomitant increase in total testosterone level.

Restoration of regular menstrual cycles prevents endometrial hyperplasia associated with anovulation. Oral contraceptives also improve acne and hirsutism.

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. Restoration of the regular menstrual cycles prevents endometrial hyperplasia associated with anovulation. Improvement of hyperandrogenic effects are seen in 60-100% of women, but usually, at least 6-12 months of use are required. 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.

Medroxyprogesterone (Depo-Provera, Provera)

Medroxyprogesterone has no effect on androgen production. Progestins stop the proliferation of endometrial cells, allowing organized sloughing of cells after withdrawal.


Selective Estrogen Receptor Modulators

Class Summary

Clomiphene citrate, a selective estrogen receptor modulator, binds to estrogen receptors, inducing ovulation by increasing the output of pituitary gonadotropins.

Clomiphene citrate (Clomid, Serophene)

Clomiphene acts directly by producing a surge of luteinizing hormone and could cause ovulation within days.


Acne Agents, Topical

Class Summary

Various topical over-the-counter (OTC) and prescription agents are available to treat acne occurring with polycystic ovarian syndrome (PCOS).

Benzoyl peroxide (Benzac AC Gel, Desquam-X, Benzac AC Wash, BenzEFoam, BPO Creamy Wash Complete Pack, BPO Foaming Cloth, BPO Gel, Clean and Clear Advantage 3-in-1 Exfoliating Cleanser, Clean and Clear Continuous Control Acne Cleanser, Clean and Clear Gel, Clearasil Vanishing Acne Treatment Cream, Lavoclen-4 Creamy Wash, Lavoclen-8 Creamy Wash, NeoBenz Micro, NeoBenz Micro SD, NeoBenz Micro Wash, Neutrogena Benzoyl Peroxide Lotion, Neutrogena Clear Pore Acne Treatment, Neutrogena On-The-Spot Acne Treatment, Neutrogena Clear Pore Daily Scrub, PanOxyl Acne Cleansing Bar, PanOxyl Acne Creamy Wash, PanOxyl Acne Foaming Wash, Proactiv, Proactiv Advanced Blemish Treatment, Proactiv Renewing Cleanser, Proactiv Repairing, Zapzyt Acne Treatment Gel)

Benzoyl peroxide elicits action by releasing active oxygen; this agent is effective in vitro against Propionibacterium acnes, an anaerobe found in sebaceous follicles and comedones. Benzoyl peroxide also elicits a keratolytic and desquamative effect, which may also contribute to its efficacy.

Tretinoin topical cream 0.02–0.1%; topical gel 0.01–0.1%; topical solution 0.05% (Retin A, Renova, Atralin, Avita, Refissa, Retin-A Micro, Tretin-X)

The exact mechanism of tretinoin is unknown. It appears to decrease cohesiveness of follicular epithelial cells with a decrease microcomedo formation. This agent also increases turnover of follicular cells to cause extrusion of comedones.

Adapalene topical cream 0.1%; gel 0.1 and 0.3%; lotion 0.1% (Differin)

Adapalene binds to specific retinoic acid nuclear receptors and modulates cellular differentiation, keratinization, and inflammatory processes. Its exact mechanism of action for treatment of acne is unknown.

Erythromycin topical 2% (AkneMycin, Ery)

Although its exact mechanism of action is unknown, erythromycin inhibits protein synthesis in susceptible organisms by reversibly binding to 50S ribosomal subunits, thereby inhibiting translocation of aminoacyl transfer-RNA and inhibiting polypeptide synthesis.

Clindamycin topical 1% (Cleocin T, ClindaReach, ClindaDerm, Clindagel, ClindaMax, Clindets, Evoclin)

Clindamycin is an antibacterial agent that binds to the 50S ribosomal subunits of susceptible bacteria and prevents elongation of peptide chains by interfering with peptidyl transfer, thereby suppressing protein synthesis. This agent reduces surface fatty acids on the skin; however, its exact mechanism of action in treating acne is unknown.

Sodium Sulfacetamide topical 10% (Klaron)

Sodium sulfacetamide is a para-aminobenzoic acid (PABA) inhibitor. This agent restricts folic acid synthesis that is required for bacterial growth.