What is the recommended evaluation and treatment approach for premenopausal women experiencing symptoms such as menstrual irregularities, mood changes, and physical discomforts, with a history of conditions like polycystic ovary syndrome (PCOS), endometriosis, or thyroid disorders?

Evaluation and Management of Premenopausal Women with Symptoms

For premenopausal women experiencing menstrual irregularities, mood changes, and physical discomforts, begin with targeted laboratory testing to exclude thyroid disorders, hyperprolactinemia, and PCOS before attributing symptoms to hormonal fluctuations, as these conditions require specific treatment approaches that differ fundamentally from general symptom management. 1, 2

Initial Laboratory Evaluation

The diagnostic workup must include specific tests to identify treatable underlying conditions:

• Measure thyroid-stimulating hormone (TSH) and free T4 to exclude thyroid dysfunction, which commonly presents with menstrual irregularity and mood changes 1, 2
• Measure prolactin using morning resting serum levels to exclude hyperprolactinemia, with confirmation requiring 2-3 samples taken 20-60 minutes apart if elevated, as prolactin suppresses GnRH pulsatility and causes anovulation 1, 2
• Measure total testosterone or free testosterone using liquid chromatography-tandem mass spectrometry (LC-MS/MS) as the first-line test for biochemical hyperandrogenism, with total testosterone showing 74% sensitivity and 86% specificity, and free testosterone demonstrating superior sensitivity of 89% with 83% specificity 1
• Measure LH and FSH between cycle days 3-6, with three estimations 20 minutes apart for accuracy, as an LH/FSH ratio >2 suggests PCOS (though this is abnormal in only 35-44% of PCOS cases) 1, 2

Critical Diagnostic Consideration for PCOS

A woman can be diagnosed with PCOS based solely on clinical hyperandrogenism (hirsutism, acne, or alopecia) plus irregular menstrual cycles, without any abnormal laboratory values, as the Rotterdam criteria require only two of three features: oligo/anovulation, clinical and/or biochemical hyperandrogenism, and polycystic ovarian morphology 1. This is crucial because:

• Total testosterone is abnormal in only 70% of women with confirmed PCOS, meaning 30% have normal testosterone levels despite having the condition 1
• If the patient has both irregular menstrual cycles AND clinical/biochemical hyperandrogenism, ultrasound is not necessary for PCOS diagnosis 1
• Clinical assessment including menstrual pattern and physical signs of hyperandrogenism remains paramount and can establish the diagnosis even when all laboratory tests return normal 1

Metabolic Screening for PCOS and Cardiovascular Risk

When PCOS is suspected or confirmed, comprehensive metabolic screening is mandatory:

• Perform a two-hour oral glucose tolerance test with 75g glucose load to screen for glucose intolerance and type 2 diabetes 1
• Obtain fasting lipid panel including total cholesterol, LDL, HDL, and triglycerides, with target LDL <100 mg/dL, HDL >35 mg/dL, and triglycerides <150 mg/dL 1
• Calculate body mass index (BMI) and measure waist-hip ratio, with WHR >0.9 indicating truncal obesity and increased cardiovascular risk 1
• Monitor cardiovascular risk factors every 6-12 months, including weight changes and blood pressure, as women with PCOS have significantly elevated cardiovascular risk 3, 1

The 2020 American College of Cardiology guidelines emphasize that PCOS confers increased cardiovascular risk through associated cardiometabolic features of abdominal obesity, diabetes, dyslipidemia, and hypertension 3.

Treatment Approach Based on Diagnosis

For PCOS with Metabolic Features:

• Use metformin for patients with cardiometabolic features such as abdominal obesity and insulin resistance (fasting glucose/insulin ratio >4) 3, 2
• Prescribe combined hormonal contraception or progestin-only contraception for menstrual irregularities and abnormal uterine bleeding 2

For Menopausal Symptoms in Premenopausal Women:

• For vasomotor symptoms (hot flashes, night sweats), prefer nonhormonal pharmacologic options as first-line therapy, including low-dose antidepressants (SSRIs/SNRIs), anticonvulsants, or certain antihypertensives 3
• Menopausal hormone therapy (MHT) can be used after consideration of risks and benefits, with combination estrogen and progestins for women with intact uterus, or estrogen alone for those without a uterus 3
• MHT is contraindicated in women with history of hormone-related cancers, abnormal vaginal bleeding, active liver disease, or active/recent history of thromboembolism 3

For Endometriosis:

Women with known endometriosis experiencing symptoms require gynecologic evaluation and may benefit from hormonal suppression or surgical management depending on symptom severity and fertility goals.

Common Pitfalls to Avoid

• Do not attribute all symptoms to PCOS without first screening for thyroid disorders and hyperprolactinemia, as these conditions require different treatment approaches 1, 2
• Do not use AMH levels as an alternative for detecting polycystic ovarian morphology or as a single test for PCOS diagnosis due to lack of standardization and significant overlap between women with and without PCOS 1
• Do not use ultrasound for PCOS diagnosis in those with gynecological age <8 years (<8 years after menarche) due to high incidence of multifollicular ovaries in this life stage 1
• Do not overlook medication effects on menstrual patterns, such as antipsychotics and depot medroxyprogesterone acetate 2
• Do not fail to account for premature menopause (age <40 years), which increases cardiovascular disease risk (HR: 1.55) and requires different management than typical premenopausal symptoms 3

Special Considerations for Iron Deficiency Anemia

If premenopausal women present with iron deficiency anemia alongside their symptoms:

• Consider bidirectional endoscopy over iron replacement therapy alone for asymptomatic premenopausal women with IDA, as studies show detection of lower gastrointestinal malignancy in 0.9% and upper gastrointestinal malignancy in 0.2% of cases 3
• This recommendation assumes no other unequivocal explanation for IDA after thorough history and physical examination, particularly considering menstrual blood loss, frequent blood donation, malabsorption syndromes, and nutritional deficiencies 3