Version May 2024
INTRODUCTION — Polycystic ovary syndrome (PCOS) should be considered in any adolescent girl with a chief complaint of hirsutism or menstrual irregularity. Acanthosis nigricans, treatment-resistant acne, scalp hair loss, or hyperhidrosis may alternatively be the chief complaint, although these features are not always present. Obesity is a common co-complaint. PCOS is diagnosed in adolescents with otherwise unexplained persistent hyperandrogenic anovulatory symptoms that are inappropriate for age and stage of adolescence [1]. (See "Definition, clinical features, and differential diagnosis of polycystic ovary syndrome in adolescents", section on 'Clinical features'.)
The diagnosis of PCOS has lifelong implications, with increased risk for infertility, metabolic syndrome, type 2 diabetes mellitus, cardiovascular events, and endometrial carcinoma [2-7].
Treatment for PCOS in adolescents is directed at the major clinical manifestations, which are:
●Abnormal uterine bleeding – Oligo-amenorrhea or excessive bleeding
●Cutaneous hyperandrogenism – Primarily hirsutism and persistent acne
●Obesity and insulin resistance
Several treatment options have been developed for each of these in adults, and some options address more than one symptom [1,3,8,9]. Few clinical trials focus on treatment of PCOS in adolescents. Recommendations for the management of PCOS in adolescents were presented by two international expert groups representing diverse professional stakeholder organizations in 2017 and 2018 [10-13]. Strategies for managing PCOS and associated symptoms in adolescents are discussed in this topic review.
Other aspects of PCOS in adolescents are discussed separately:
●(See "Diagnostic evaluation of polycystic ovary syndrome in adolescents".)
●(See "Etiology and pathophysiology of polycystic ovary syndrome in adolescents".)
MANAGEMENT OVERVIEW — The choice of therapy for PCOS depends upon the individual adolescent's clinical presentation and their goals and preferences [11]. If possible, treatment is initiated only after evaluating for PCOS (algorithm 1) [1,14]. Persistent hyperandrogenemia and anovulation are required to confirm the diagnosis of PCOS; however, in some cases, the symptoms are sufficiently severe (eg, excessive uterine bleeding) to require prompt empiric treatment with combined oral contraceptive pills (COCs) before persistent hyperandrogenic anovulation can be documented. Because this treatment masks hyperandrogenemia and anovulatory symptoms, pretreatment diagnostic screening should be initiated to the extent possible. In this way, a provisional diagnosis of PCOS can be made. (See "Diagnostic evaluation of polycystic ovary syndrome in adolescents".)
After the patient reaches gynecologic maturity, the diagnosis of PCOS can be confirmed by demonstrating hyperandrogenic menstrual abnormality during a trial off COC treatment for at least three months [11,15].
If a trial off of COC is attempted, it should be coupled with contraceptive counseling because the infertility of PCOS is relative, not absolute.
Goals of treatment include addressing each of the following major symptoms:
●Abnormal uterine bleeding – First-line treatment for PCOS is ordinarily estrogen-progestin COCs since these treat both menstrual abnormalities and hyperandrogenemia (table 1) [9,11,16,17]. Anovulatory symptoms manifest as oligo-amenorrhea and/or excessive menstrual bleeding. The thresholds for defining these abnormal uterine bleeding patterns in adolescents are discussed separately (table 2). (See "Definition, clinical features, and differential diagnosis of polycystic ovary syndrome in adolescents", section on 'Anovulation'.)
•Oligo-amenorrhea – Oligo-amenorrhea should be treated in adolescents with PCOS, not only for psychosocial reasons, but because chronic anovulation increases the risk of developing endometrial hyperplasia, which is associated with endometrial carcinoma. Progestin is the critical ingredient in COCs that inhibits endometrial proliferation; it prevents the hyperplasia that results from unopposed estrogen action. (See "Endometrial hyperplasia: Clinical features, diagnosis, and differential diagnosis" and "Endometrial carcinoma: Epidemiology, risk factors, and prevention", section on 'Risk factors'.)
•Excessive menstrual bleeding – Excessive menstrual bleeding due to ovulatory dysfunction is a common manifestation of PCOS and often is the initial presenting complaint (table 2). If the bleeding puts the patient at risk for anemia, higher doses of estrogen are sometimes needed. Heavy uterine bleeding can cause severe anemia requiring hospital admission. COCs or progestin-only regimens are usually effective in managing this symptom. However, transfusion, antifibrinolytic, or invasive treatment occasionally may be required [18]. (See "Definition, clinical features, and differential diagnosis of polycystic ovary syndrome in adolescents", section on 'Anovulation' and "Abnormal uterine bleeding in adolescents: Management".)
Prior to initiation of a COC, side effects and risks should be discussed, including the small but increased risk of venous thromboembolism (VTE) (table 1). For most patients with PCOS, the benefits of COCs outweigh the potential risks of VTE. A detailed discussion of the risks and side effects of COCs is presented separately. (See "Combined estrogen-progestin contraception: Side effects and health concerns".)
Although PCOS is a risk factor for thromboembolism in adults [19], VTE is rare in adolescents (1 per 4000 patient-years of contraceptive use or 3.3 per 1000 hospital discharges) [20,21]. Risk factors include a family history of VTE, a history of migraine headaches with aura, obesity, smoking, autoimmune disease, immobilization, or hospitalization for surgery or infection [22-24].
While progestin-only treatments may be used to control menstrual irregularity, they are generally less effective in PCOS than COCs because they do not reduce serum free testosterone as well as COCs do, and the androgen excess of PCOS interferes with progesterone-mediated slowing of the gonadotropin-releasing hormone pulse generator [25,26]. The side effects and risks of progestin-only methods are presented separately. (See "Contraception: Progestin-only pills (POPs)", section on 'Counseling points' and "Contraception: Etonogestrel implant" and "Intrauterine contraception: Background and device types", section on 'Levonorgestrel IUD' and "Depot medroxyprogesterone acetate (DMPA): Efficacy, side effects, metabolic impact, and benefits", section on 'Weight changes'.)
●Cutaneous hyperandrogenism – Over one-half of adolescents with PCOS have hirsutism or moderate-to-severe acne vulgaris. Medical endocrine therapy improves these manifestations, decreasing the effect of excess androgens by:
•Reducing androgen production
•Reducing serum free androgen levels
•Blocking androgen action at the level of target organs (eg, hair follicle)
COCs also treat hyperandrogenemia, accomplishing the first two of these goals (table 1) [16,17]. They lower serum free testosterone levels by decreasing ovarian production of total testosterone and by increasing serum sex hormone-binding globulin levels. They also modestly lower dehydroepiandrosterone sulfate (DHEAS) levels. Reducing androgen levels hinders the further transformation of vellus to terminal hairs, which occurs with androgen exposure. In most patients with PCOS, treatment with COCs can be expected to arrest progression of hirsutism, reduce the need for shaving by approximately one-half, and improve acne within three months.
Antiandrogenic therapy, which inhibits binding of androgen to its receptor, is indicated for patients with hirsutism that does not respond sufficiently to COC treatment or for patients who are on progestin-only contraception [16]. If this is not successful, direct hair removal is the next step.
●Acne – The treatment of acne in patients with PCOS is the same as in patients without PCOS and is discussed separately. (See "Acne vulgaris: Overview of management".)
Adolescents with acne resistant to topical treatments should be evaluated for androgen excess before the initiation of hormonal treatment [1]. Hyperandrogenemia would, in most cases, be due to PCOS and be an indication for COC treatment. Patients with refractory acne may also benefit from antiandrogens. (See 'Hirsutism without abnormal uterine bleeding' below.)
●Obesity and insulin resistance – Obesity aggravates the insulin resistance and menstrual dysfunction of PCOS. Approved treatments that reduce insulin resistance improve ovulation moderately and hyperandrogenemia slightly. Diet and exercise are first-line treatment to address obesity in adolescents with PCOS [10,27]. If the abnormal glucose tolerance cannot be normalized by lifestyle modification, the addition of metformin may be helpful. Glucagon-like peptide 1 agonists that are markedly superior to medications previously available for the induction of weight loss are approved for the treatment of adolescent obesity. These hold promise for the management of the obesity in PCOS. (See 'Treatment of obesity and insulin resistance' below.)
TREATMENT OF ABNORMAL UTERINE BLEEDING AND HIRSUTISM — Combination oral contraceptives (COCs), which contain estrogen and progestin, are usually the first-line treatment for adolescents with PCOS associated abnormal menstrual bleeding and/or cutaneous signs of androgen excess (table 1) [8,9,16]. The estrogen-progestin combination suppresses the hypothalamic-pituitary-ovarian axis and reduces excess androgen production by the ovary, which improves menstrual regularity and decreases anovulatory uterine bleeding, hirsutism, and acne. The progestin component also inhibits gonadotropin secretion. This prevents endometrial proliferation, preventing hyperplasia and the associated risk of carcinoma.
Metformin alone may be considered if the main objective is menstrual cycle regulation, although evidence of efficacy is limited [9]. Rarely, alternative interventions such as gonadotropin-releasing hormone agonist therapy or glucocorticoid therapy are used instead of COCs or progestin-only plus antiandrogen treatment. This should be done in collaboration with an endocrinologist.
Abnormal uterine bleeding
Oligo-amenorrhea with hirsutism — Our approach in patients who have oligo-amenorrhea with hirsutism depends upon whether the patient has any estrogen contraindications. These contraindications are rare in the absence of a family history of venous thromboembolism (VTE), a history of migraine headaches with aura, or obesity associated with the comorbidities discussed above. A complete list of contraindications is discussed separately. (See 'Management overview' above and "Combined estrogen-progestin contraception: Side effects and health concerns", section on 'Contraindications' and "Combined estrogen-progestin oral contraceptives: Patient selection, counseling, and use", section on 'Eligibility'.)
●Estrogen not contraindicated – In these patients, we use a combined estrogen-progestin method such as a combination oral contraceptive (COC) (table 1); however, a combined estrogen-progestin contraceptive vaginal ring or transdermal patch are acceptable alternatives. Our choice is in line with International and Endocrine Society guidelines that suggest COCs as first-line pharmacologic therapy for menstrual irregularity [8,9,11] and hirsutism [11,16].
We suggest selecting a COC that contains 30 to 35 mcg of ethinyl estradiol because COCs containing ≤20 mcg may be less effective in controlling irregular menstrual bleeding, particularly in obese hyperandrogenic adolescents, and may limit bone accrual (table 1) [28,29]. All COCs are effective for treating hirsutism and acne [16,30].
In our experience, menstrual abnormalities are usually well controlled within one to two months of starting COC treatment. COC therapy will normalize androgen levels within 18 to 21 days. We suggest rechecking serum free testosterone in the third week of COC treatment (note that an unchanged or increased total testosterone level can be misleading due to the expected elevation of sex hormone-binding globulin [SHBG] caused by estrogen). Other experts do not recheck androgen levels [9]. Due to escape from ovarian suppression during the pill-free interval, occasional patients require an extended-cycle COC to control severe hyperandrogenemia [31].
If treatment is not successful in reducing androgen levels, the patient's PCOS either has an unusually prominent component of functional adrenal hyperandrogenism or the diagnosis of PCOS should be questioned. For such patients, we suggest referral to an endocrinologist for further evaluation. (See "Diagnostic evaluation of polycystic ovary syndrome in adolescents", section on 'Further evaluation by endocrinology subspecialists for rare disorders mimicking PCOS'.)
If the patient's hirsutism does not improve, we suggest the addition of an antiandrogen, such as spironolactone (table 3). Spironolactone in combination with a COC substantially reduces hirsutism (on average the score is reduced by one-third) (figure 1), although there is considerable individual variation [32]. The decision to add an antiandrogen to a COC depends on the severity of the hirsutism and considerations of efficacy, side effects, and costs. (See "Management of hirsutism in premenopausal women".)
●Estrogen contraindicated – In these patients, we treat with a progestin-only contraceptive to prevent endometrial hyperplasia and an antiandrogen to treat hirsutism (table 3). Unlike COCs, oral progestins have no therapeutic effect on hirsutism; therefore, these patients will likely need the addition of an antiandrogen, such as spironolactone. Because antiandrogens have the potential to feminize a male fetus, the progestin-only contraceptive provides the added benefit of reducing the likelihood of an unintended pregnancy while the patient is taking a teratogenic agent.
Any progestin-only contraceptive can be prescribed; however, the levonorgestrel intrauterine device (IUD) and the etonogestrel implant have the advantage of providing long-acting reversible contraception. (See "Contraception: Etonogestrel implant" and "Intrauterine contraception: Background and device types", section on 'Levonorgestrel IUD' and "Contraception: Progestin-only pills (POPs)" and "Depot medroxyprogesterone acetate (DMPA): Formulations, patient selection and drug administration".)
Available antiandrogens include the following (table 3):
•Spironolactone – We generally prescribe spironolactone, the most widely used antiandrogen for this purpose, because it is safer than flutamide and cyproterone and probably more effective than finasteride [16,33,34]. The randomized controlled trials and meta-analyses demonstrating the benefit of spironolactone are discussed separately. (See "Management of hirsutism in premenopausal women", section on 'Antiandrogens'.)
Guidelines suggest that a dose at the upper end of the therapeutic range (ie, 100 to 200 mg given in two divided doses daily) is required to treat hirsutism; however, we suggest starting at a dose of 25 to 50 mg daily and titrating upward as tolerated and based on patient response [16]. Approximately 9 to 12 months of therapy is required to achieve the maximal effect because of the long growth cycles of sexual hair follicles. After one year of therapy, the dose can be reduced gradually for maintenance therapy. We suggest halving the dose and re-evaluating for change every six months. Spironolactone must be administered as long as the patient wishes to maintain improvement in hirsutism, and 100 mg daily is probably the minimally effective dose for maintenance.
Spironolactone is usually well tolerated at these doses, but fatigue and hyperkalemia rarely limit its usefulness in some patients. Laboratory testing for electrolytes and creatinine should be performed two to four weeks after initiation of spironolactone therapy to determine whether the spironolactone dose should be lowered.
•Second-line antiandrogens – Second-line antiandrogens include finasteride, flutamide, and cyproterone acetate.
-Finasteride – Finasteride interferes with androgen action by competitively inhibiting 5 alpha-reductase type 1, which converts testosterone to its active form, dihydrotestosterone. Finasteride was slightly less effective than spironolactone in some studies on the treatment of patients with hirsutism. However, meta-analysis of the limited available data has not shown a significant difference in efficacy between these treatments [16]. The usual dose is 2.5 to 5 mg daily but can be increased to 7.5 mg.
-Cyproterone acetate – Cyproterone acetate is a progestin with antiandrogenic activity that is sometimes used for the treatment of hirsutism. It is not available in the United States but is available in Canada and Mexico as a COC containing ethinyl estradiol and low-dose cyproterone acetate (5 mg; Diane [brand name]). It also is available in Europe in this form and as a high-dose (50 mg) progestin tablet that is combined with any form of estrogen. Drug regulatory agencies in Europe have recommended limiting its use to "second-line" therapy because of a perceived increase in risk of hepatotoxicity compared with other available progestins [35,36]. In addition, high-dose cyproterone acetate is associated with a small increase in the risk of meningioma and is contraindicated in people with a history of meningioma. (See "Management of hirsutism in premenopausal women", section on 'Suggested drug: spironolactone' and "Epidemiology, pathology, clinical features, and diagnosis of meningioma", section on 'High-dose cyproterone'.)
-Flutamide – Flutamide is another competitive inhibitor of androgen-receptor action. Its use has been limited by expense and the rare risk of fatal hepatocellular toxicity [37]. Flutamide may permit ovulation in patients with PCOS; however, its utility for patients who wish to conceive is limited by the potential risk of feminization of the male fetus. The Endocrine Society hirsutism guidelines recommend against the routine use of flutamide because of its potential hepatotoxicity, expense, and the availability of other effective antiandrogens [16]. While it has been argued that low-dose flutamide is safe [38], the population studied is too small to be certain. There is less experience with newer, more potent and selective antiandrogens [39,40]. (See "Management of hirsutism in premenopausal women".)
A more detailed discussion of these antiandrogens in the treatment of hirsutism is discussed separately. (See "Management of hirsutism in premenopausal women", section on 'Antiandrogens'.)
If the patient's hirsutism persists, the patient's PCOS either has an unusually prominent component of functional adrenal hyperandrogenism or the diagnosis of PCOS should be questioned. For such patients, we suggest referral to an endocrinologist for further evaluation. (See "Diagnostic evaluation of polycystic ovary syndrome in adolescents", section on 'Further evaluation by endocrinology subspecialists for rare disorders mimicking PCOS'.)
The optimal duration of treatment has not been determined. Whereas PCOS ordinarily persists, little is known about the natural history of PCOS diagnosed in adolescence, particularly in mild cases. We advise continuing treatment until the patient is gynecologically mature (five years following menarche) or has lost a substantial amount of excess weight if obesity is a coexisting condition. We then consider a trial off of treatment for a few months. If the patient does not resume a normal menstrual cycle, restarting treatment is appropriate. If a trial off of hormonal contraception is attempted, it should be coupled with contraceptive counseling because the infertility of PCOS is relative, not absolute.
Oligo-amenorrhea without hirsutism — Our approach in patients who have oligo-amenorrhea without hirsutism is based upon whether the patient desires contraception and whether the patient has any estrogen contraindications. The primary goal for treatment of this group is to prevent endometrial hyperplasia, which can lead to endometrial carcinoma.
●Contraception needed – Patients who have contraindications to estrogen are limited to progestin-only methods, while patients without estrogen contraindications may choose any hormonal method. These contraindications are rare in the absence of a family history of VTE, a history of migraine headaches with aura, or obesity associated with the comorbidities discussed above. A complete list of contraindications is discussed separately. (See 'Management overview' above and "Combined estrogen-progestin contraception: Side effects and health concerns", section on 'Contraindications' and "Combined estrogen-progestin oral contraceptives: Patient selection, counseling, and use", section on 'Eligibility'.)
•Estrogen not contraindicated – In these patients, we use a combined estrogen-progestin method such as a COC (table 3); however, a combined estrogen-progestin contraceptive vaginal ring or transdermal patch are acceptable alternatives. Our choice is in line with International and Endocrine Society guidelines that suggest COCs as first-line pharmacologic therapy for menstrual irregularity [8,9,11].
We suggest selecting a COC that contains 30 or 35 mcg of ethinyl estradiol because COCs containing ≤20 mcg ethinyl estradiol may be less effective in controlling irregular menstrual bleeding, particularly in obese hyperandrogenic girls, and may limit bone accrual (table 1).
•Estrogen contraindicated – In these patients, we treat with a progestin-only contraceptive to prevent endometrial hyperplasia (table 3). Any progestin-only contraceptive can be prescribed; however, the levonorgestrel IUD and the etonogestrel implant have the advantage of providing long-acting reversible contraception. (See "Contraception: Etonogestrel implant" and "Intrauterine contraception: Background and device types", section on 'Levonorgestrel IUD' and "Contraception: Progestin-only pills (POPs)" and "Depot medroxyprogesterone acetate (DMPA): Formulations, patient selection and drug administration".)
●Contraception not needed – Even when contraception is not needed, a COC is still recommended as a first-line treatment to control endometrial cycling. An alternative is to prescribe a progestin-only pill for the first 7 to 10 days of each month or of every other month (table 3). Treatment with cyclic oral progestins relies on their direct inhibitory effects on endometrial proliferation. Withdrawal bleeding can be expected to occur within a few days of the last progestin dose. Although these patients may prefer to have long intervals between their menses, it is essential that they have a withdrawal bleed at least every two months to prevent endometrial hyperplasia.
Patients must be informed that oral progestin prescribed to regulate menstrual cyclicity (ie, 7 to 10 days each month) is not a means of contraception.
•Medroxyprogesterone acetate (Provera [brand name]; 10 mg given orally at bedtime to reduce nausea)
•Norethindrone acetate (Aygestin [brand name]; 2.5 to 10 mg given orally daily)
•Micronized progesterone (Prometrium [brand name]; 100 to 200 mg given orally at bedtime to reduce nausea)
Cyclic progestin therapy on an every-other-month cycle can also permit the detection of an emerging normal menstrual cycle. The optimal duration of treatment has not been determined. Whereas PCOS ordinarily persists, little is known about the natural history of PCOS diagnosed in adolescence, particularly in mild cases. We advise continuing treatment until the patient is gynecologically mature (five years following menarche) or has lost a substantial amount of excess weight if obesity is a coexisting condition. We then consider a trial off of treatment for a few months. If the patient does not resume a normal menstrual cycle, restarting treatment is appropriate. If a trial off of hormonal contraception is attempted, it should be coupled with contraceptive counseling because the infertility of PCOS is relative, not absolute.
Metformin alone is another option if the main objective is menstrual cycle regulation, although evidence is limited [9]. In two small trials that compared metformin with lifestyle counseling for three to six months in adolescents with PCOS, metformin increased the likelihood of menses, although the effect was not statistically significant in one of the trials [41,42].
The metformin starting dose is 500 mg daily and is gradually increased by 500 mg per week as tolerated, to a maximum dose of 1000 to 2000 mg daily. Metformin should be taken with the evening meal to minimize nausea, which is the cause of an approximately 15 percent discontinuation rate. Higher doses are often better tolerated when divided into two daily doses or when given in an extended-release form [43].
Excessive bleeding with hirsutism — Our approach in patients who have excessive bleeding with hirsutism depends upon whether the patient has any estrogen contraindications. These contraindications are rare in the absence of a family history of VTE, a history of migraine headaches with aura, or obesity associated with the comorbidities discussed above. A complete list of contraindications is discussed separately. (See 'Management overview' above and "Combined estrogen-progestin contraception: Side effects and health concerns", section on 'Contraindications' and "Combined estrogen-progestin oral contraceptives: Patient selection, counseling, and use", section on 'Eligibility'.)
●Estrogen not contraindicated – In these patients, we use a combined estrogen-progestin method such as a combined COC (table 1). Although a combined estrogen-progestin contraceptive vaginal ring or transdermal patch are acceptable alternatives, the estrogen doses required to treat acute, excessive abnormal uterine bleeding may be three- to fourfold higher than the doses needed to treat oligo-amenorrhea. Management of acute excessive uterine bleeding is discussed separately. (See "Abnormal uterine bleeding in adolescents: Management".)
After control is achieved, maintenance should be attempted at a lower estrogen dose because higher doses of estrogen increase the risk of VTE, particularly in patients who are overweight or obese [44]. We suggest selecting a COC that contains 30 or 35 mcg of ethinyl estradiol because COCs containing ≤20 mcg ethinyl estradiol may be less effective in controlling heavy menstrual bleeding, particularly in obese hyperandrogenic adolescents, and may limit bone accrual (table 1). All COCs are effective for treating hirsutism and acne [16,30].
In our experience, menstrual abnormalities are usually well controlled within one to two months of starting COC treatment. COC therapy will normalize androgen levels within 18 to 21 days. We suggest rechecking serum free testosterone late in the third week of COC treatment (note that an unchanged or increased total testosterone level can be misleading due to the elevation of SHBG by estrogen). Other experts do not recheck androgen levels [9]. Due to escape from ovarian suppression during the pill-free interval, occasional patients require an extended-cycle COC to control severe hyperandrogenemia [31].
If treatment is not successful in reducing androgen levels, the patient's PCOS either has an unusually prominent component of functional adrenal hyperandrogenism or the diagnosis of PCOS should be questioned. For such patients, we suggest referral to an endocrinologist for further evaluation. (See "Diagnostic evaluation of polycystic ovary syndrome in adolescents", section on 'Further evaluation by endocrinology subspecialists for rare disorders mimicking PCOS'.)
If the patient's hirsutism does not improve, we suggest the addition of an antiandrogen, such as spironolactone (table 3). Spironolactone in combination with a COC substantially reduces hirsutism (on average the score is reduced by one-third) (figure 1), although there is considerable individual variation [32]. The decision to add an antiandrogen to a COC depends on the severity of the hirsutism and considerations of efficacy, side effects, and costs. (See "Management of hirsutism in premenopausal women".)
●Estrogen contraindicated – For patients with acute heavy bleeding and estrogen contraindications, several progestin-only regimens are available (table 3). Among the available oral progestin-only alternatives, we typically use norethindrone acetate because it is a potent menstrual-suppressive agent. However, since it is partially metabolized to ethinyl estradiol, a history of VTE is a contraindication to its use. Dosing and tapering regimens for norethindrone acetate are discussed separately. (See "Abnormal uterine bleeding in adolescents: Management", section on 'Progestin-only pills'.)
Once the acute bleeding has been controlled, any progestin-only contraceptive can be prescribed; however, the 52 mg levonorgestrel IUD is not only approved for treatment of heavy menstrual bleeding, but it also, like the etonogestrel implant, has the advantage of providing long-acting reversible contraception. (See "Contraception: Etonogestrel implant" and "Intrauterine contraception: Background and device types", section on 'Levonorgestrel IUD' and "Contraception: Progestin-only pills (POPs)" and "Depot medroxyprogesterone acetate (DMPA): Formulations, patient selection and drug administration".)
Unlike COCs, progestin-only methods have no therapeutic effect on hirsutism; therefore, these patients will likely need the addition of an antiandrogen, such as spironolactone. Because antiandrogens have the potential to feminize a male fetus, progestin-only contraceptives provide the added benefit of reducing the likelihood of an unintended pregnancy while the patient is taking a teratogenic agent.
Available antiandrogens include the following (table 3):
•Spironolactone – We generally prescribe spironolactone, the most widely used antiandrogen for this purpose, because it is safer than flutamide and cyproterone and probably more effective than finasteride [16,34]. The randomized controlled trials and meta-analysis demonstrating the benefit of spironolactone are discussed separately. (See "Management of hirsutism in premenopausal women", section on 'Antiandrogens'.)
Guidelines suggest that a dose at the upper end of the therapeutic range (ie, 100 to 200 mg given in two divided doses daily) is required to treat hirsutism; however, we suggest starting at a dose of 25 to 50 mg daily and titrating upward as tolerated and based on patient response [16]. Approximately 9 to 12 months of therapy is required to achieve the maximal effect because of the long growth cycles of sexual hair follicles. After one year of therapy, the dose can be reduced gradually for maintenance therapy. We suggest halving the dose and re-evaluating for change every six months. Spironolactone must be administered as long as the patient wishes to maintain improvement in hirsutism, and 100 mg daily is probably the minimally effective dose for maintenance.
Spironolactone is usually well tolerated at these doses, but fatigue and hyperkalemia rarely limit its usefulness in some patients. Laboratory testing of electrolytes and creatinine should be performed two to four weeks after initiation of spironolactone therapy to determine whether the spironolactone dose should be lowered.
•Second-line antiandrogens – Second-line antiandrogens include finasteride, flutamide, and cyproterone acetate.
-Finasteride – Finasteride interferes with androgen action by competitively inhibiting 5 alpha-reductase type 1, which converts testosterone to its active form, dihydrotestosterone. Finasteride was slightly less effective than spironolactone in some studies on the treatment of patients with hirsutism. However, meta-analysis of the limited available data has not shown a significant difference in efficacy between these treatments [16]. The usual dose is 2.5 to 5 mg daily but can be increased to 7.5 mg.
-Cyproterone acetate – Cyproterone acetate is a progestin with antiandrogenic activity that is sometimes used for the treatment of hirsutism. It is not available in the United States but is available in Canada and Mexico as a COC containing ethinyl estradiol and low-dose cyproterone acetate (5 mg; Diane [brand name]). It also is available in Europe in this form and as a high-dose (50 mg) progestin tablet that is combined with any form of estrogen. Drug regulatory agencies in Europe have recommended limiting its use to "second-line" therapy because of a perceived increase in risk of hepatotoxicity compared with other available progestins [35,36]. In addition, high-dose cyproterone acetate is associated with a small increase in the risk of meningioma and is contraindicated in people with a history of meningioma. (See "Management of hirsutism in premenopausal women", section on 'Suggested drug: spironolactone' and "Epidemiology, pathology, clinical features, and diagnosis of meningioma", section on 'High-dose cyproterone'.)
-Flutamide – Flutamide is another competitive inhibitor of androgen-receptor action. Its use has been limited by expense and the rare risk of fatal hepatocellular toxicity [37]. Flutamide may permit ovulation in patients with PCOS; however, its utility for patients who wish to conceive is limited by the potential risk of feminization of the male fetus. The Endocrine Society hirsutism guidelines recommend against the routine use of flutamide because of its potential hepatotoxicity, expense, and the availability of other effective antiandrogens [16]. While it has been argued that low-dose flutamide is safe [38], the population studied is too small to be certain. There is less experience with newer, more potent and selective antiandrogens [39,40]. (See "Management of hirsutism in premenopausal women".)
A more detailed discussion of these antiandrogens in the treatment of hirsutism is discussed separately. (See "Management of hirsutism in premenopausal women", section on 'Antiandrogens'.)
If the patient's hirsutism persists, the patient's PCOS either has an unusually prominent component of functional adrenal hyperandrogenism or the diagnosis of PCOS should be questioned. For such patients, we suggest referral to an endocrinologist for further evaluation. (See "Diagnostic evaluation of polycystic ovary syndrome in adolescents", section on 'Further evaluation by endocrinology subspecialists for rare disorders mimicking PCOS'.)
Gynecologic referral is indicated for patients who have uncontrollable abnormal bleeding despite COC therapy or whose bleeding cannot be controlled medically.
The optimal duration of treatment has not been determined. Whereas PCOS ordinarily persists, little is known about the natural history of PCOS diagnosed in adolescence, particularly in mild cases. We advise continuing treatment until the patient is gynecologically mature (five years following menarche) or has lost a substantial amount of excess weight if obesity is a coexisting condition. We then consider a trial off of treatment for a few months. If the patient does not resume a normal menstrual cycle, restarting treatment is appropriate. If a trial off of hormonal contraception is attempted, it should be coupled with contraceptive counseling because the infertility of PCOS is relative, not absolute.
Excessive bleeding without hirsutism — Our approach in patients who have excessive bleeding without hirsutism depends upon whether the patient has any estrogen contraindications. These contraindications are rare in the absence of a family history of VTE, a history of migraine headaches with aura, or obesity associated with the comorbidities discussed above. A complete list of contraindications is discussed separately. (See 'Management overview' above and "Combined estrogen-progestin contraception: Side effects and health concerns", section on 'Contraindications' and "Combined estrogen-progestin oral contraceptives: Patient selection, counseling, and use", section on 'Eligibility'.)
●Estrogen not contraindicated – In these patients, we use a combined estrogen-progestin method such as a combined COC (table 1). Although a combined estrogen-progestin contraceptive vaginal ring or transdermal patch are acceptable alternatives, the estrogen doses required to treat acute, excessive abnormal uterine bleeding may be three- to fourfold higher than the doses needed to treat oligo-amenorrhea. (See "Abnormal uterine bleeding in adolescents: Management".)
After control is achieved, maintenance should be attempted at a lower estrogen dose because higher doses of estrogen increase the risk of VTE, particularly in patients who are overweight or obese [44]. We suggest selecting a COC that contains 30 to 35 mcg of ethinyl estradiol because COCs containing ≤20 mcg ethinyl estradiol may be less effective in controlling heavy menstrual bleeding, particularly in obese hyperandrogenic adolescents (table 1).
●Estrogen contraindicated – For patients with acute heavy bleeding and estrogen contraindications, several progestin-only regimens are available (table 3). Among the available oral progestin-only alternatives, we typically use norethindrone acetate because it is a potent menstrual suppressive agent. However, since it is partially metabolized to ethinyl estradiol, a history of VTE is a contraindication to use. Dosing and tapering regimens for norethindrone acetate are discussed separately. (See "Abnormal uterine bleeding in adolescents: Management", section on 'Progestin-only pills'.)
Once the acute bleeding has been controlled, any progestin-only contraceptive can be prescribed; however, the 52 mg levonorgestrel IUD is not only approved for treatment of heavy menstrual bleeding, but it also, like the etonogestrel implant, has the advantage of providing long-acting reversible contraception. (See "Contraception: Etonogestrel implant" and "Intrauterine contraception: Background and device types", section on 'Levonorgestrel IUD' and "Contraception: Progestin-only pills (POPs)" and "Depot medroxyprogesterone acetate (DMPA): Formulations, patient selection and drug administration".)
Metformin alone is another option if the main objective is to maintain menstrual cycle regulation, although evidence is limited [9]. In two small trials that compared metformin with lifestyle counseling for three to six months in adolescents with PCOS, metformin increased the likelihood of menses, although the effect was not statistically significant in one of the trials [41,42].
The metformin starting dose is 500 mg daily and is gradually increased by 500 mg per week, as tolerated, to a maximum dose of 1000 to 2000 mg daily. Metformin should be taken with the evening meal to minimize nausea, which is the cause of an approximately 15 percent discontinuation rate. Higher doses are often better tolerated when divided into two daily doses or when given in an extended-release form [43].
Gynecologic referral is indicated for patients who have uncontrollable abnormal bleeding despite COC therapy or whose bleeding cannot be controlled medically.
The optimal duration of treatment has not been determined. Whereas PCOS ordinarily persists, little is known about the natural history of PCOS diagnosed in adolescence, particularly in mild cases. We advise continuing treatment until the patient is gynecologically mature (five years following menarche) or has lost a substantial amount of excess weight if obesity is a coexisting condition. We then consider a trial off of treatment for a few months. If the patient does not resume a normal menstrual cycle, restarting treatment is appropriate. If a trial off of hormonal contraception is attempted, it should be coupled with contraceptive counseling because the infertility of PCOS is relative, not absolute.
Hirsutism without abnormal uterine bleeding — Our approach in patients who have hirsutism depends upon whether the patient has any estrogen contraindications. These contraindications are rare in the absence of a family history of VTE, a history of migraine headaches with aura, or obesity associated with the comorbidities discussed above. A complete list of contraindications is discussed separately. (See 'Management overview' above and "Combined estrogen-progestin contraception: Side effects and health concerns", section on 'Contraindications' and "Combined estrogen-progestin oral contraceptives: Patient selection, counseling, and use", section on 'Eligibility'.)
●Estrogen not contraindicated – In these patients, we use a combined estrogen-progestin method such as a COC (table 1); however, the combined estrogen-progestin contraceptive vaginal ring or transdermal patch are acceptable alternatives. Although all hormonal treatment for hirsutism is off-label in the United States [16,45], our choice is in line with International and Endocrine Society guidelines that suggest COCs as first-line pharmacologic therapy for hirsutism [9,11,16].
We suggest selecting a COC that contains 30 to 35 mcg of ethinyl estradiol because COCs containing ≤20 mcg ethinyl estradiol may limit bone accrual (table 1). All COCs are effective for treating hirsutism [16,30].
In our experience, COC therapy will normalize androgen levels within 18 to 21 days. We suggest rechecking serum free testosterone late in the third week of COC treatment (note that an unchanged or increased total testosterone level can be misleading due to the elevation of SHBG by estrogen). Other experts do not recheck androgen levels [9]. Due to escape from ovarian suppression during the pill-free interval, occasional patients require an extended-cycle COC to control severe hyperandrogenemia [31].
If treatment is not successful in reducing androgen levels, the patient's PCOS either has an unusually prominent component of functional adrenal hyperandrogenism or the diagnosis of PCOS should be questioned. For such patients, we suggest referral to an endocrinologist for further evaluation. (See "Diagnostic evaluation of polycystic ovary syndrome in adolescents", section on 'Further evaluation by endocrinology subspecialists for rare disorders mimicking PCOS'.)
If the patient's hirsutism does not improve, we suggest the addition of an antiandrogen, such as spironolactone (table 3). Spironolactone in combination with a COC substantially reduces hirsutism (on average the score is reduced by one-third) (figure 1), although there is considerable individual variation [32]. The decision to add an antiandrogen to a COC depends on the severity of the hirsutism and considerations of efficacy, side effects, and costs. (See "Management of hirsutism in premenopausal women".)
●Estrogen contraindicated – In these patients, we treat with an antiandrogen such as spironolactone (table 3). Because antiandrogens have the potential to feminize a male fetus, a progestin-only contraceptive should be added to reduce the likelihood of an unintended pregnancy while the patient is taking a teratogenic agent (table 3).
Any progestin-only contraceptive can be prescribed; however, the levonorgestrel IUD and the etonogestrel implant have the advantage of providing long-acting reversible contraception. (See "Contraception: Etonogestrel implant" and "Intrauterine contraception: Background and device types", section on 'Levonorgestrel IUD' and "Contraception: Progestin-only pills (POPs)" and "Depot medroxyprogesterone acetate (DMPA): Formulations, patient selection and drug administration".)
Available antiandrogens include the following (table 3):
•Spironolactone – We generally prescribe spironolactone, the most widely used antiandrogen for this purpose, because it is safer than flutamide and cyproterone and probably more effective than finasteride [16,34]. The randomized controlled trials and meta-analysis demonstrating the benefit of spironolactone are discussed separately. (See "Management of hirsutism in premenopausal women", section on 'Antiandrogens'.)
Guidelines suggest that a dose at the upper end of the therapeutic range (ie, 100 to 200 mg given in two divided doses daily) is required to treat hirsutism; however, we recommend starting at a lower dose of 25 to 50 mg daily and titrating upward as tolerated and based on patient response [16]. Approximately 9 to 12 months of therapy is required to achieve the maximal effect because of the long growth cycles of sexual hair follicles. After one year of therapy, the dose can be reduced gradually for maintenance therapy. We suggest halving the dose and re-evaluating for change every six months. Spironolactone must be administered as long as the patient wishes to maintain improvement in hirsutism, and 100 mg daily is probably the minimally effective dose for maintenance.
Spironolactone is usually well tolerated at these doses, but fatigue and hyperkalemia rarely limit its usefulness in some patients. Laboratory testing of electrolytes and creatinine should be performed two to four weeks after initiation of spironolactone therapy to determine whether the spironolactone dose should be lowered.
•Second-line antiandrogens – Second-line antiandrogens include finasteride, cyproterone acetate, and flutamide.
-Finasteride – Finasteride interferes with androgen action by competitively inhibiting 5 alpha-reductase type 1, which converts testosterone to its active form, dihydrotestosterone. Finasteride was slightly less effective than spironolactone in some studies on the treatment of patients with hirsutism. However, meta-analysis of the limited available data has not shown a significant difference in efficacy between these treatments [16]. The usual dose is 2.5 to 5 mg daily but can be increased to 7.5 mg.
-Cyproterone acetate – Cyproterone acetate is a progestin with antiandrogenic activity that is sometimes used for the treatment of hirsutism. It is not available in the United States but is available in Canada and Mexico as a COC containing ethinyl estradiol and low-dose cyproterone acetate (5 mg; Diane [brand name]). It also is available in Europe in this form and as a high-dose (50 mg) progestin tablet that is combined with any form of estrogen. Drug regulatory agencies in Europe have recommended limiting its use to "second-line" therapy because of a perceived increase in risk of hepatotoxicity compared with other available progestins [35,36]. In addition, high-dose cyproterone acetate is associated with a small increase in the risk of meningioma and is contraindicated in people with a history of meningioma. (See "Management of hirsutism in premenopausal women", section on 'Suggested drug: spironolactone' and "Epidemiology, pathology, clinical features, and diagnosis of meningioma", section on 'High-dose cyproterone'.)
-Flutamide – Flutamide is another competitive inhibitor of androgen receptor action. Its use has been limited by expense and the rare risk of fatal hepatocellular toxicity [37]. Flutamide may permit ovulation in patients with PCOS; however, its utility for patients who wish to conceive is limited by the potential risk of feminization of the male fetus. The Endocrine Society hirsutism guidelines recommend against the routine use of flutamide because of its potential hepatotoxicity, expense, and the availability of other effective antiandrogens [16]. While it has been argued that low-dose flutamide is safe [38], the population studied is too small to be certain. There is less experience with newer, more potent and selective antiandrogens [39,40]. (See "Management of hirsutism in premenopausal women".)
A more detailed discussion of these antiandrogens in the treatment of hirsutism is discussed separately. (See "Management of hirsutism in premenopausal women", section on 'Antiandrogens'.)
If the patient's hirsutism persists, the patient's PCOS either has an unusually prominent component of functional adrenal hyperandrogenism or the diagnosis of PCOS should be questioned. For such patients, we suggest referral to an endocrinologist for further evaluation. (See "Diagnostic evaluation of polycystic ovary syndrome in adolescents", section on 'Further evaluation by endocrinology subspecialists for rare disorders mimicking PCOS'.)
If hirsutism is not controlled satisfactorily within six months, then direct hair removal measures can be added [17]. The costs of these treatments are not covered by third-party payers. The decision among these options depends upon patient preference, including cost of the measure, tolerance of discomfort/pain, risk of complications, and outcome. The 2018 Endocrine Society clinical guidelines for the treatment of hirsutism suggest supplementing antiandrogen therapy with direct hair removal therapy if necessary in hyperandrogenic women, such as those with PCOS [16]. More detailed discussions and options for direct hair removal are found separately. (See "Management of hirsutism in premenopausal women", section on 'Antiandrogens' and "Removal of unwanted hair", section on 'Temporary methods'.)
The natural history of PCOS (ie, untreated) is a slow decrease of androgens over the reproductive lifespan. Consequently, hirsutism is unlikely to resolve, and some form of ongoing therapy is needed to minimize hair growth.
TREATMENT OF OBESITY AND INSULIN RESISTANCE
Obesity — For overweight and obese patients with PCOS, weight management is a major treatment goal [10,27]. Healthy lifestyle interventions are essential and often require attention to psychosocial and behavioral factors [10,12]. Nevertheless, substantial and sustained improvements in weight or glycemic control are difficult to achieve, even when a lifestyle intervention program with family involvement is undertaken [27] or when metformin is combined with behavior modification [41,46]. (See "Prevention and management of childhood obesity in the primary care setting".)
As with the treatment of any individual with obesity, there seems to be no advantage to a low glycemic index or low-carbohydrate diet over a low-fat diet [47,48]; rather, a reduction of both carbohydrate and fat intake in the context of a high-quality diet of natural foods is indicated [27,49]. Patients with obesity typically experience improvement in their anovulatory symptoms roughly in proportion to the amount of weight lost [47]. Improvement in hyperandrogenism is minimal, however [16,48].
Bariatric surgery is indicated for adolescent patients with body mass index (BMI) ≥35 or 120 percent of the 95th percentile for age and sex with comorbid conditions and BMI ≥40 or 140 percent of the 95th percentile for age and sex without comorbid conditions and access to centers that specialize in bariatric surgery in this age group for patients who have failed medical therapy [27,50]. (See "Obesity in adults: Behavioral therapy" and "Obesity in adults: Role of physical activity and exercise" and "Obesity in adults: Dietary therapy" and "Surgical management of severe obesity in adolescents".)
Impaired glucose tolerance — Patients with PCOS, obesity, and impaired glucose tolerance who have not responded to diet and exercise may benefit from adjunctive treatment with metformin [11,51,52] or glucagon-like peptide 1 (GLP-1) receptor agonists. There are several methods to assess for impaired glucose tolerance. A hemoglobin A1c result of 5.7 to 6.5 percent or a two-hour blood glucose result of 140 to 199 mg/dL on an oral glucose tolerance test is diagnostic of impaired glucose tolerance. In patients with PCOS and impaired glucose tolerance, we suggest treatment with metformin.
●Metformin – Metformin is an insulin sensitizer with many additional actions; however, treatment of impaired glucose tolerance is an off-label use. Type 2 diabetes is the only indication for which metformin is approved by the US Food and Drug Administration. Metformin primarily lowers insulin levels by reducing hepatic glucose production [53-57]. It also promotes ovulation and lowers androgen levels modestly (by approximately 20 percent) [42,58-60]. (See "Etiology and pathophysiology of polycystic ovary syndrome in adolescents", section on 'Insulin-resistant hyperinsulinism'.)
•Metformin dose and monitoring – The metformin starting dose is 500 mg daily. It should be taken with the evening meal to minimize nausea, which is the cause of an approximately 15 percent discontinuation rate. The dose is gradually increased by 500 mg per week, as tolerated, to a maximum dose of 1000 to 2000 mg daily. Higher doses are often better tolerated when divided into two daily doses or when given in an extended-release form [43].
We suggest obtaining a comprehensive metabolic panel at baseline because of the rare complication of lactic acidosis [37]. Metformin is contraindicated in patients with impaired hepatic or renal function, alcoholism, or cardiopulmonary insufficiency because it can cause lactic acidosis in these settings.
•Clinical effectiveness – Metformin is minimally effective for PCOS in the absence of weight control [61]; variability in weight control may explain the inconsistent effects of metformin treatment on insulin levels [42,62,63]. (See "Metformin for treatment of the polycystic ovary syndrome".)
●Promising therapies
•GLP-1 receptor agonists – GLP-1 receptor agonists are approved for the treatment of obesity (semaglutide, liraglutide) or type 2 diabetes (liraglutide, exenatide) in adolescents.
The most effective of these agents, semaglutide, holds potential for the treatment of impaired glucose tolerance; however, this is an off-label use and may not be covered by insurance. This agent may be best used in collaboration with a pediatric endocrinologist. (See "Prevention and management of childhood obesity in the primary care setting", section on 'Pharmacotherapy' and "Management of type 2 diabetes mellitus in children and adolescents", section on 'Trials of GLP-1 agonists'.)
•Myo-inositol – Some dieticians recommend myo-inositol, a dietary supplement, for the treatment of obesity and/or impaired glucose tolerance. The dose is 2 g twice daily for eight weeks.
Myo-inositol appears to be safe. In the one trial of women with PCOS, myo-inositol improved ovulatory frequency by approximately twofold compared with placebo [64,65].
OTHER RESOURCES — The following online resources are available to patients with PCOS and their families:
●PCOS Resources for a Healthier You – From the Center for Young Women's Health of Boston Children's Hospital [66]
●Polycystic Ovary Syndrome: A Guide for Families – From the Pediatric Endocrine Society and the American Academy of Pediatrics [67]
●ASK PCOS – Evidence-based information for women with PCOS (website and app) [68]
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Polycystic ovary syndrome" and "Society guideline links: Hirsutism".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Polycystic ovary syndrome (The Basics)")
●Beyond the Basics topic (see "Patient education: Polycystic ovary syndrome (PCOS) (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Overview – Several treatment options are available for adolescents with polycystic ovary syndrome (PCOS) (table 1 and table 3). The choice of therapy depends on the individual adolescent's symptoms, goal for treatment, and preferences (eg, cost).
●Treatment of abnormal uterine bleeding with or without hirsutism – In adolescents who experience the menstrual and/or cutaneous symptoms of PCOS, we suggest the use of estrogen-progestin combination oral contraceptives (COCs) as first-line treatment rather than other therapies (table 1) (Grade 2C).
•Oligo-amenorrhea with hirsutism
-Patients without a contraindication to estrogen – We prescribe a combined estrogen-progestin contraceptive.
-Patients with a contraindication to estrogen – We prescribe a progestin-only contraceptive with an antiandrogen (table 3); among antiandrogens, we suggest spironolactone rather than other antiandrogens (Grade 2C).
(See 'Oligo-amenorrhea with hirsutism' above.)
•Oligo-amenorrhea without hirsutism
-Patients interested in contraception without an estrogen contraindication – We prescribe a COC (table 1).
-Patients interested in contraception with an estrogen contraindication – We prescribe a progestin-only contraceptive (table 3).
-Patients not interested in contraception – We prescribe cyclic progestin or a cyclic combined estrogen-progestin contraceptive (the latter is not an option if there is an estrogen contraindication).
(See 'Oligo-amenorrhea without hirsutism' above.)
•Excessive bleeding with hirsutism
-Patients without a contraindication to estrogen – We prescribe a combined estrogen-progestin contraceptive (table 1). If the bleeding puts the patient at risk for anemia, higher doses of estrogen are sometimes needed.
-Patients with a contraindication to estrogen – We prescribe a progestin-only contraceptive with an antiandrogen (typically spironolactone as above) (table 3).
(See 'Excessive bleeding with hirsutism' above.)
•Excessive bleeding without hirsutism
-Patients without a contraindication to estrogen – We prescribe a combined estrogen-progestin contraceptive (table 1). If the bleeding puts the patient at risk for anemia, higher doses of estrogen are sometimes needed.
-Patients with a contraindication to estrogen – We prescribe a progestin-only contraceptive (table 3).
(See 'Excessive bleeding without hirsutism' above.)
●Treatment of hirsutism without abnormal uterine bleeding
•Patients without a contraindication to estrogen – We prescribe a combined estrogen-progestin contraceptive (table 1). The effects of hormone treatments on hirsutism are maximal after 9 to 12 months of therapy. If the response to a combined hormonal method is not adequate, we add an antiandrogen (spironolactone as above).
•Patients with a contraindication to estrogen – We prescribe a progestin-only contraceptive with an antiandrogen (spironolactone as above) (table 3).
(See 'Hirsutism without abnormal uterine bleeding' above.)
●Treatment of obesity and impaired glucose tolerance
•Weight loss improves menstrual regularity, acanthosis nigricans, and hyperandrogenemia. Lifestyle recommendations (eg, exercise and diet) are the same as in patients without PCOS.
•In patients for whom weight loss does not occur despite lifestyle recommendations, we test for impaired glucose tolerance. If impaired glucose tolerance is diagnosed (hemoglobin A1c result of 5.7 to 6.5 percent or a two-hour blood glucose result of 140 to 199 mg/dL on an oral glucose tolerance test), we suggest treatment with metformin (Grade 2C). (See 'Treatment of obesity and insulin resistance' above.)
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