Premenopausal Lab Work for Irregular Cycles, Hot Flashes, and Mood Changes
For a premenopausal woman aged 35-50 presenting with irregular menstrual cycles, hot flashes, and mood changes, begin with FSH, LH, estradiol, prolactin, TSH, and mid-luteal progesterone to identify treatable endocrine causes of menstrual irregularity. 1
Initial Hormonal Panel
The core evaluation should include:
FSH and LH: Measure serum levels between cycle days 3-6, ideally using three samples taken 20 minutes apart for accuracy 2, 1. An LH/FSH ratio >2 suggests polycystic ovary syndrome (PCOS), while FSH >35 IU/L indicates premature ovarian insufficiency 2
Estradiol: Obtain during the early follicular phase (days 3-6) to establish baseline ovarian function 1. Low estradiol with elevated FSH confirms ovarian insufficiency 2
Prolactin: Measure as a morning resting sample (not post-stress or postictal) 2, 1. Levels >20 μg/L are abnormal and require exclusion of hypothyroidism or pituitary pathology 2. Hyperprolactinemia can mimic PCOS by suppressing GnRH pulsatility and causing anovulation 3
TSH and free T4: Critical first-line test as hypothyroidism causes both fatigue and menstrual irregularity, and occurs in 43% of women with hyperprolactinemia 1, 3. Primary hypothyroidism should be treated first, as this alone may normalize prolactin and restore menses 3
Mid-luteal progesterone: Obtain during the mid-luteal phase according to the menstrual cycle 2, 1. Levels <6 nmol/L indicate anovulation, commonly caused by PCOS, hypothalamic amenorrhea, or hyperprolactinemia 2
Additional Testing Based on Clinical Features
If hirsutism, acne, obesity (BMI >25), or truncal obesity (waist-hip ratio >0.9) are present:
Testosterone: Measure total testosterone on cycle days 3-6 2, 1. Levels >2.5 nmol/l suggest PCOS or non-classical adrenal hyperplasia 2
DHEAS: Markedly elevated levels (>3800 ng/ml for ages 20-29, >2700 ng/ml for ages 30-39) suggest non-classical congenital adrenal hyperplasia or adrenal/ovarian tumor 2, 1
Androstenedione: Levels >10.0 nmol/l warrant exclusion of adrenal or ovarian tumor 2
Fasting glucose and insulin: Obtain fasting morning levels with glucose/insulin ratio calculation 2, 1. Fasting glucose >7.8 mmol/l suggests diabetes, and glucose/insulin ratio >4 indicates reduced insulin sensitivity associated with PCOS 2, 3
Imaging and Specialized Testing
Pelvic ultrasound: Perform transvaginal or transabdominal ultrasound between cycle days 3-9 if initial labs suggest PCOS or to exclude ovarian pathology 2, 1. Findings of >10 peripheral cysts (2-8 mm diameter) with thickening of ovarian stroma indicate polycystic ovaries 2
Anti-Müllerian hormone (AMH): May provide information on ovarian reserve, though interpretation requires caution in women <25 years due to significant fluctuations 2, 1. Low AMH levels indicate incipient ovarian insufficiency 2
Common Pitfalls to Avoid
Do not confuse isolated polycystic ovaries (17-22% of general population) with PCOS, which requires both polycystic ovaries AND symptoms/hormonal abnormalities. 2 PCOS affects 4-6% of the general population and requires hyperandrogenism, chronic anovulation, and metabolic dysregulation 2.
Always start with TSH/free T4 before attributing symptoms to other causes, as thyroid dysfunction is highly prevalent and treatable 1, 3. If prolactin is elevated, repeat testing and rule out hypothyroidism before pursuing pituitary imaging 2, 3.
Menstrual charting for at least 6 months is essential to document patterns: <23 days indicates polymenorrhea, >35 days indicates oligomenorrhea, and >6 months without bleeding indicates amenorrhea 2.
When to Refer
Refer to endocrinology and/or gynecology if: