Summary
PMOS is much more than a disorder of the ovaries. It is a complex endocrine, reproductive and metabolic syndrome that can affect health throughout a woman’s life. Early diagnosis is important not only for the treatment of menstrual disturbances, androgen-related symptoms and infertility, but also for the early detection and management of diabetes, cardiovascular risk factors and other associated disorders.
Polyendocrine Metabolic Ovarian Syndrome (PMOS), formerly known as Polycystic Ovary Syndrome (PCOS), is one of the most common endocrine and metabolic disorders in women. In May 2026, the condition was internationally renamed from PCOS to PMOS. The new terminology better reflects the fact that the disorder involves not only the ovaries but also several hormonal and metabolic systems, and that the ovarian structures traditionally described as “cysts” are actually small follicles rather than true cysts.[1]
PMOS affects approximately 10–13% of women of reproductive age. Despite its high prevalence, up to 70% of affected women worldwide may remain undiagnosed.[2,3] PMOS is an important cause of ovulatory dysfunction and infertility, but its consequences extend far beyond reproduction and include metabolic, cardiovascular, dermatological and psychological aspects.
Women with PMOS may present with a combination of the following features:
It is important to note that 17-hydroxyprogesterone is not a marker of androgen excess used to establish the diagnosis of PMOS. It is primarily measured to exclude non-classic congenital adrenal hyperplasia, an important differential diagnosis.[4]
Diagnostic criteria in adults
According to the modified Rotterdam criteria, PMOS can be diagnosed in adult women when at least two of the following three features are present, after other disorders that can produce similar symptoms have been excluded:
Table 1. Diagnostic criteria and recommended investigations in PMOS
Diagnostic area | Recommended assessment | Interpretation / practical considerations |
Ovulatory dysfunction | Menstrual history and cycle length | In adult women, repeatedly occurring cycles shorter than 21 days or longer than 35 days, or fewer than 8 menstrual cycles per year, indicate ovulatory dysfunction. If cycles appear regular but anovulation is suspected, serum progesterone may be measured in the luteal phase.[1,4] |
Clinical hyperandrogenism | Assessment for hirsutism, acne and androgen-related scalp hair loss | Hirsutism is the most specific clinical manifestation of androgen excess. Acne and female-pattern hair loss may support the diagnosis but are less specific when occurring in isolation.[4] |
Biochemical hyperandrogenism | Total testosterone and free testosterone or calculated free androgen index (FAI) | These are the preferred biochemical tests. High-quality assays, preferably LC-MS/MS for total testosterone, should be used where available. If testosterone is normal despite clinical suspicion, androstenedione and/or DHEAS may be considered.[4] |
Polycystic ovarian morphology (PCOM) | Transvaginal ultrasound in adults when required | With modern high-frequency transducers, PCOM is generally defined by ≥20 follicles measuring 2–9 mm in at least one ovary and/or an ovarian volume ≥10 mL. Thresholds depend on ultrasound technology.[1,4] |
AMH | Serum anti-Müllerian hormone in adults | AMH may be used as an alternative to ultrasound to identify PCOM in adults. AMH should not be used as a stand-alone diagnostic test and should not be combined routinely with ultrasound merely to increase the probability of diagnosis.[1,4] |
When ultrasound or AMH is unnecessary | — | If both ovulatory dysfunction and clinical/biochemical hyperandrogenism are already present in an adult woman, ultrasound or AMH is generally not required to establish the diagnosis.[4] |
Pregnancy exclusion | β-hCG when appropriate | Pregnancy should be excluded in women with amenorrhea or relevant menstrual disturbance.[1] |
Thyroid disease | TSH; free T4 when indicated | Used to exclude hypothyroidism or hyperthyroidism as causes of menstrual disturbance.[1,4] |
Hyperprolactinemia | Serum prolactin | Elevated prolactin can cause amenorrhea, oligomenorrhea and occasionally galactorrhea.[1,4] |
Non-classic congenital adrenal hyperplasia | Early-morning 17-hydroxyprogesterone; ACTH stimulation test when indicated | 17-hydroxyprogesterone is used for differential diagnosis and is not a diagnostic androgen marker for PMOS.[1,4] |
Primary ovarian insufficiency | FSH ± estradiol when clinically indicated | Particularly relevant in women with amenorrhea, vasomotor symptoms or suspected premature ovarian insufficiency.[1] |
Cushing syndrome | Appropriate cortisol testing, e.g. 1-mg overnight dexamethasone suppression test, when clinically suspected | Routine screening is not required in every woman with PMOS; testing should be guided by characteristic clinical features.[1] |
Androgen-producing ovarian/adrenal tumor | Testosterone, DHEAS and further endocrine/imaging evaluation when indicated | Consider particularly with rapid onset or rapidly progressive virilization, severe hyperandrogenism or markedly elevated androgen concentrations.[1,4] |
Glycemic status | 75-g OGTT, HbA1c and/or fasting glucose | Glycemic status should be assessed at diagnosis and reassessed every 1–3 years according to individual risk. The 75-g OGTT is the most sensitive test. It is particularly important before pregnancy/fertility treatment and should be repeated during pregnancy as recommended.[1,4] |
Insulin resistance | No routine fasting insulin, HOMA-IR or other insulin-resistance assays | Although insulin resistance is central to PMOS pathophysiology, currently available insulin assays have limited value in routine clinical care and are not recommended for routine diagnosis.[1,4] |
Cardiovascular risk | Blood pressure and fasting or non-fasting lipid profile | A lipid profile should be obtained at diagnosis irrespective of age or BMI. Blood pressure should generally be measured at least annually and when pregnancy is planned.[1,4] |
Body weight and adiposity | BMI and, where appropriate, waist circumference | Used to assess metabolic risk and guide individualized weight-management strategies. Normal body weight does not exclude PMOS or insulin resistance.[1,4] |
Associated conditions | Clinical assessment for sleep apnea, depression, anxiety, eating disorders and other relevant comorbidities | Screening should be guided by symptoms and individual risk because PMOS is associated with important psychological, metabolic and sleep-related comorbidities.[1,4] |
Adolescents | Persistent ovulatory dysfunction and hyperandrogenism | Diagnosis is more restrictive in adolescents. Ultrasound and AMH should not be used to diagnose PMOS during adolescence because physiological pubertal changes reduce specificity.[4] |
If both irregular menstrual cycles and hyperandrogenism are already present, ultrasound examination or AMH measurement is generally not required to establish the diagnosis.[4]
Other possible causes of irregular menstruation or androgen excess should be excluded. Depending on the clinical situation, investigations may include TSH, prolactin, 17-hydroxyprogesterone and FSH, with additional testing for disorders such as Cushing syndrome or androgen-producing adrenal or ovarian tumors when clinically indicated.[4]
The diagnostic approach is different in adolescents. Because irregular cycles and multifollicular ovaries may be physiological during puberty, both persistent ovulatory dysfunction and hyperandrogenism are required. Ultrasound and AMH should not be used for diagnosis in adolescents because of insufficient specificity.[4]
PMOS should not be regarded solely as a gynecological disorder. Insulin resistance and metabolic abnormalities are central components of the syndrome in many affected women.
Insulin resistance means that tissues such as skeletal muscle, adipose tissue and the liver respond less effectively to insulin. The pancreas therefore produces more insulin to maintain normal blood glucose levels. This compensatory hyperinsulinemia can stimulate ovarian androgen production and reduce hepatic production of sex hormone-binding globulin (SHBG), thereby increasing biologically active androgens. A vicious circle involving insulin resistance, androgen excess and visceral adiposity may develop.
Overweight and obesity are common but are not required for the diagnosis. According to the 2026 German guideline, approximately 38–69% of women with PMOS are affected by obesity, depending on population and ethnic background.[1] Importantly, lean women can also have PMOS and insulin resistance.
Women with PMOS have an increased risk of:
The German guideline states that disorders of glucose metabolism, including prediabetes, type 2 diabetes and gestational diabetes, occur approximately three times more frequently in women with PMOS than in women without the disorder. This increased risk exists independently of body weight but rises further in the presence of obesity.[1]
For this reason, glucose metabolism should be assessed when PMOS is diagnosed and subsequently at intervals of approximately one to three years, depending on individual risk. Assessment may include fasting glucose, HbA1c and, particularly in women at increased risk or planning pregnancy, a 75-g oral glucose tolerance test (OGTT).[1]
A lipid profile should also be obtained irrespective of age or BMI, and blood pressure should be checked regularly, generally at least annually.[1]
Treatment should be individualized according to the predominant symptoms, metabolic risk, body weight, cardiovascular risk and whether pregnancy is currently desired. PMOS is therefore best managed through an interdisciplinary approach involving gynecology, endocrinology and, where appropriate, diabetology, reproductive medicine, dermatology, nutritional medicine and psychological support.[1]
Table 2. Treatment of PMOS according to the predominant clinical problem
Clinical problem | Preferred management | Additional options and important considerations |
Cycle disturbance / chronic anovulation | Healthy lifestyle measures for all women. In women not currently seeking pregnancy, combined hormonal contraceptives are generally first-line treatment for irregular menstrual cycles when no contraindications are present.[1,4] | Endometrial protection is important when prolonged anovulation is present. Cyclic progestogens, progestogen-only contraception or a levonorgestrel-releasing intrauterine system may be used when combined hormonal contraception is unsuitable. Metformin can improve cycle regularity but is generally less effective for this purpose than hormonal contraception.[1] |
Hyperandrogenism: hirsutism, acne, androgen-related hair loss | Combined hormonal contraceptives are generally first-line pharmacological treatment in women who are not trying to conceive and have no contraindications.[1,4] | Cosmetic hair-removal methods, laser/light therapies and topical treatments may be added. Antiandrogens such as spironolactone can be considered when symptoms remain inadequately controlled or hormonal contraception is unsuitable; reliable contraception is essential because of potential fetal effects. Metformin may modestly improve androgen-related symptoms but is generally less effective than hormonal or specific antiandrogen therapy.[1,4] |
Insulin resistance / metabolic risk / prediabetes / type 2 diabetes risk | Lifestyle intervention including healthy nutrition, physical activity and prevention of excess weight gain is fundamental. Cardiovascular risk factors, hypertension, dyslipidemia and diabetes should be treated according to the relevant disease-specific guidelines.[1,4] | Metformin may be considered particularly in women with BMI ≥25 kg/m², impaired glucose metabolism, high metabolic risk or type 2 diabetes. It may also be used in selected women irrespective of BMI. Glycemic status should be reassessed every 1–3 years according to risk. Routine measurement of insulin concentrations or HOMA-IR is not recommended for clinical management.[1,4] |
Overweight / obesity | Individualized nutrition, physical activity and behavioral interventions are first-line therapy. A 5–10% reduction in body weight can improve metabolic health and may improve ovulatory function and fertility in women with overweight or obesity.[1,4] | Anti-obesity pharmacotherapy may be considered according to approved indications and general obesity guidelines. Incretin-based therapies such as liraglutide, semaglutide or tirzepatide may be appropriate in selected patients. Reliable contraception is required during treatment when pregnancy is possible, and drug-specific discontinuation periods should be observed before conception. Bariatric/metabolic surgery may be considered according to obesity guidelines in women with severe obesity.[1] |
Infertility due to anovulation | Letrozole is the preferred first-line pharmacological treatment for ovulation induction in women with anovulatory PMOS and no other major infertility factors.[1,4] | Clomiphene citrate and/or gonadotropins are alternatives when letrozole is ineffective, contraindicated or unavailable. Metformin may improve ovulation and pregnancy rates in some women, particularly when metabolic abnormalities coexist, but more effective ovulation-induction agents are available. IVF/ICSI may be considered when first- and second-line approaches fail or when additional infertility factors are present. Preconception weight, glucose metabolism, blood pressure, folate intake and other risk factors should be optimized.[1,4] |
Lifestyle intervention
Healthy nutrition, regular physical activity and behavioral interventions form the foundation of treatment for all women with PMOS, irrespective of body weight. Exercise and dietary modification can improve insulin sensitivity, cardiovascular risk factors and general well-being even when substantial weight loss does not occur.[1,4]
In women with overweight or obesity, even a moderate reduction in body weight can improve metabolic parameters, menstrual regularity and fertility. For women with overweight who wish to become pregnant, the German guideline recommends aiming for a weight reduction of approximately 5–10% before conception when appropriate.[1]
Combined hormonal contraceptives
For women who are not currently trying to conceive, combined hormonal contraceptives are an important treatment option for irregular menstrual cycles and symptoms of androgen excess. They can regulate menstrual bleeding and improve acne and hirsutism by reducing ovarian androgen production and increasing SHBG.
However, combined hormonal contraceptives primarily treat reproductive and androgen-related symptoms and should not be regarded as treatment for the underlying insulin resistance. The preparation should be selected according to the woman’s individual cardiovascular, thromboembolic and metabolic risk.[1,4]
In women with chronic anovulation, adequate endometrial protection is particularly important. Depending on the individual situation, this may be achieved with combined hormonal contraception, cyclic progestogens, progestogen-only contraception or a levonorgestrel-releasing intrauterine system.[1]
Metformin
Metformin has been used for decades in the treatment of type 2 diabetes and improves insulin sensitivity, particularly in the liver. It can also be used in women with PMOS, especially when metabolic abnormalities, insulin resistance, impaired glucose tolerance, an increased risk of type 2 diabetes or overweight/obesity are present.[1,4]
According to the 2026 German guideline, metformin may be considered in women with PMOS and a BMI of 25 kg/m² or higher to support weight and metabolic management, even in the absence of type 2 diabetes. It may also reduce the risk of progression toward type 2 diabetes.[1]
Metformin can modestly reduce androgen levels and may improve menstrual regularity, acne or hirsutism. However, for androgen-related symptoms and cycle regulation it is generally less effective than combined hormonal contraceptives or specific antiandrogen treatment.[1]
Metformin usually produces only modest weight loss; lifestyle intervention remains essential. Gastrointestinal adverse effects such as nausea, abdominal discomfort and diarrhea are common, particularly at the beginning of treatment. Gradual dose escalation improves tolerability. Long-term treatment can also be associated with vitamin B12 deficiency, so vitamin B12 measurement should be considered when clinical risk factors or symptoms are present.[4]
In Germany, use of metformin specifically for PMOS in the absence of another approved indication is generally an off-label use. Patients should be informed about the expected benefits, potential adverse effects, alternatives and the off-label status, and the discussion and consent should be documented. Reimbursement cannot be assumed solely on the basis of a PMOS diagnosis and depends on the indication and individual payer arrangements.[1]
Weight-loss medication
For women with overweight or obesity, pharmacological obesity treatment may also be considered according to the approved indications and current obesity guidelines. The 2026 German PMOS guideline specifically discusses incretin-based therapies such as liraglutide, semaglutide and tirzepatide. These drugs should not be regarded as PMOS-specific therapies but can be valuable for treating coexisting obesity or type 2 diabetes.[1]
Reliable contraception is required during treatment with incretin-based weight-loss medication when pregnancy is possible, and appropriate discontinuation intervals must be observed before a planned pregnancy depending on the drug.[1]
PMOS is one of the most common causes of anovulatory infertility. Nevertheless, most women with PMOS can become pregnant either spontaneously or with appropriate treatment.[2]
If infertility is caused by absent or infrequent ovulation, letrozole is currently the preferred first-line pharmacological treatment for ovulation induction. Clomiphene and gonadotropins are alternatives when letrozole is ineffective or unsuitable.[1,4]
Metformin can improve ovulation in some women and may support fertility treatment, particularly when metabolic abnormalities are also present. However, metformin should not generally replace letrozole as first-line ovulation-induction therapy.[1,4]
Women with PMOS who become pregnant have an increased risk of several pregnancy complications, including gestational diabetes, hypertensive disorders and pre-eclampsia, and therefore require appropriate obstetric monitoring.[1,4]