What hormones should be tested in a 33-year-old female patient on birth control (hormonal contraception) with secondary amenorrhea, hot flashes, fatigue, brain fog, irritability, and weight gain, despite normal thyroid function tests?

Hormonal Testing for Secondary Amenorrhea in a 33-Year-Old on Birth Control

In a 33-year-old woman on hormonal contraception with secondary amenorrhea and symptoms of hot flashes, fatigue, brain fog, irritability, and weight gain, you should test FSH, LH, estradiol, prolactin, and consider DHEA-S and testosterone to rule out premature ovarian insufficiency, hyperprolactinemia, and hyperandrogenism, despite the confounding effect of exogenous hormones. 1, 2, 3

Critical Context: Birth Control Complicates Interpretation

• Hormonal contraceptives suppress the hypothalamic-pituitary-ovarian axis, making interpretation of sex hormone levels challenging while on treatment. 4
• Amenorrhea on birth control is expected and typically benign, but her constellation of symptoms (hot flashes, fatigue, brain fog) suggests possible underlying pathology that predated or exists independently of contraceptive use. 4
• The key question is whether she has true ovarian insufficiency or another endocrine disorder that the birth control is masking. 1, 3

Recommended Hormonal Panel

Essential First-Line Tests (While Still on Birth Control):

• Prolactin: Hyperprolactinemia accounts for 20% of secondary amenorrhea cases and can cause all her symptoms. The threshold for abnormal is >20 μg/L. 5, 6
• FSH and LH: Ideally measured as an average of three samples taken 20 minutes apart. FSH >40 mIU/mL indicates primary ovarian insufficiency, which can occur even at age 33. 7, 5
• Estradiol: Low levels suggest ovarian insufficiency; this helps distinguish true premature ovarian failure from contraceptive-induced suppression. 7, 2

Additional Tests to Consider:

• DHEA-S and total/free testosterone: Elevated androgens suggest PCOS or adrenal pathology. DHEA-S is primarily adrenal in origin, and marked elevation warrants further adrenal evaluation. 5, 6
• Morning cortisol or 24-hour urine cortisol: Her symptom cluster (weight gain, fatigue, irritability) could suggest Cushing's syndrome, which can present with amenorrhea and central hypogonadism. 8

Optimal Testing Strategy

The most accurate approach is to have her discontinue hormonal contraception for 6-8 weeks before testing, then repeat the hormonal panel. 1, 9, 3

• If she cannot or will not stop contraception, proceed with testing now, but interpret results cautiously knowing that exogenous hormones will suppress FSH, LH, and estradiol. 4
• If prolactin is elevated (>20 μg/L), repeat as a morning resting sample to confirm, as stress can cause spurious elevation. 5, 6
• If prolactin remains elevated on repeat testing, order pituitary MRI to exclude prolactinoma. Prolactin >4,000 mU/L typically indicates prolactinoma. 5, 6

Critical Pitfalls to Avoid

• Do not assume amenorrhea on birth control is benign without investigating her systemic symptoms. Hot flashes at age 33 are particularly concerning for premature ovarian insufficiency. 7, 3
• Amenorrhea following oral contraceptive use does not imply causation—investigation should aim at determining the underlying cause, not attributing it to "post-pill amenorrhea." 9
• Hyperprolactinemia itself causes anovulation by suppressing kisspeptin and gonadotropin secretion, making it difficult to distinguish from PCOS initially. 5, 6
• If FSH is elevated suggesting ovarian insufficiency, patients can maintain unpredictable ovarian function and should not be presumed infertile—they may still need contraception. 1, 3

ICD-10 Coding

Use N91.1 (Secondary amenorrhea) as the primary diagnosis. 1, 3

Additional codes to consider based on symptoms:

• R61 (Generalized hyperhidrosis) for hot flashes
• R53.83 (Fatigue)
• R41.840 (Attention and concentration deficit) for brain fog
• R45.4 (Irritability and anger)
• E66.9 (Obesity, unspecified) or R63.5 (Abnormal weight gain) if applicable

If testing reveals specific pathology:

• E28.310 (Symptomatic premature menopause) if FSH >40 mIU/mL
• E22.1 (Hyperprolactinemia) if prolactin elevated
• E28.2 (Polycystic ovarian syndrome) if criteria met after stopping contraception

Follow-Up Algorithm

1. If prolactin >20 μg/L: Repeat morning resting sample → If confirmed elevated, order pituitary MRI. 5, 6
2. If FSH >40 mIU/mL: Diagnose premature ovarian insufficiency → Consider hormone replacement therapy for bone and cardiovascular protection. 7, 3
3. If androgens elevated: Evaluate for PCOS (after stopping contraception) or adrenal pathology. 5, 6
4. If all hormones normal on contraception: Have her stop birth control for 6-8 weeks and reassess to determine if she has spontaneous menses. 1, 3