Is hormone testing beneficial for a female patient of reproductive age with amenorrhea who is currently on birth control (Combined Oral Contraceptive (COC))?

Hormone Testing in Amenorrhea While on Birth Control

Hormone testing provides no clinically useful information for a patient on combined oral contraceptives (COCs) for amenorrhea, as the exogenous hormones suppress and mask the hypothalamic-pituitary-ovarian axis, making interpretation impossible. 1

Why Hormone Testing is Not Beneficial

Suppression of Normal Hormonal Patterns

• COCs suppress gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) through negative feedback, preventing accurate assessment of the underlying cause of amenorrhea. 2

• Exogenous estrogen and progesterone from COCs mask baseline reproductive hormone levels, making it impossible to determine whether the patient has hypothalamic dysfunction, ovarian failure, or polycystic ovary syndrome. 3

• The hormonal contraceptive creates an artificial hormonal environment that bears no relationship to the patient's endogenous reproductive function. 1

Guidelines Do Not Recommend Testing While on COCs

• CDC guidelines classify hormone testing (glucose, lipids, liver enzymes, hemoglobin, thrombogenic mutations) as "Class C" for combined hormonal contraception initiation, meaning these tests "do not contribute substantially to safe and effective use of the contraceptive method." 1

• No examinations or laboratory tests beyond blood pressure measurement are considered essential for safe COC use in healthy women. 1

• Ovarian function cannot be reliably assessed during hormonal replacement therapy for contraception or gonadal failure. 1

When Hormone Testing IS Appropriate

After Discontinuing COCs

• Women should stop hormonal contraceptives at least 2 months before testing if assessing baseline reproductive function. 3

• For patients who remain amenorrheic after discontinuing COCs for one year, or who develop symptoms of gonadal failure, hormone testing becomes clinically useful. 1

• Initial workup after COC discontinuation should include FSH, LH, prolactin, and thyroid-stimulating hormone levels, along with a pregnancy test. 4

Specific Hormone Testing Protocols Off COCs

• FSH and LH: Measure between cycle days 3-6 (or if amenorrheic, at any time after 2 months off COCs), with accurate assessment calculated as the average of three estimations taken 20 minutes apart. 3

• Progesterone: Mid-luteal phase measurement (approximately 7 days after suspected ovulation) is the most reliable indicator of ovulation, with levels <6 nmol/L indicating anovulation. 3

• Diagnostic patterns: FSH >35 IU/L and LH >11 IU/L suggest ovarian failure; LH:FSH ratio >2 suggests polycystic ovary syndrome; LH <7 IU/mL may indicate hypothalamic dysfunction. 3

Clinical Algorithm for Managing Amenorrhea on COCs

If Patient Desires Continued Contraception

• Continue COCs without hormone testing, as the amenorrhea is expected and the COC is providing appropriate treatment. 2

• Monitor blood pressure regularly as the only essential safety parameter. 1, 2

• Prescribe up to one year's supply of COCs at a time. 2

If Patient Desires Fertility Assessment

• Discontinue COCs and wait at least 2 months before any hormone testing. 3

• Monitor for return of spontaneous menses for up to one year. 1

• If amenorrhea persists beyond one year off COCs, or if symptoms of gonadal failure develop, proceed with comprehensive hormone evaluation including FSH, LH, prolactin, TSH, and pregnancy test. 4

If Underlying Diagnosis is Unknown

• If the original cause of amenorrhea was never established before starting COCs, discontinue the COC for 2 months and perform comprehensive evaluation. 3

• Consider anti-Müllerian hormone (AMH) testing for patients with irregular cycles, as AMH does not vary by menstrual day and is not affected by exogenous estrogen or progesterone. 3

Common Pitfalls to Avoid

• Do not order FSH, LH, estradiol, or progesterone levels while the patient is actively taking COCs – these results will be artificially suppressed and uninterpretable. 1, 3

• Do not assume amenorrhea on COCs indicates treatment failure – withdrawal bleeding on COCs is not true menstruation and its absence does not indicate pathology. 2

• Do not confuse COC-induced amenorrhea with pathological amenorrhea – the COC itself causes endometrial suppression that may result in no withdrawal bleeding, which is a benign side effect, not a medical concern. 2

• Do not test prolactin levels while on COCs if hyperprolactinemia is suspected – estrogen in COCs can elevate prolactin levels by 28% (median), confounding interpretation. 5