What does measuring additional hormones, such as Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH), testosterone, and Dehydroepiandrosterone Sulfate (DHEA-S), indicate about ovarian versus peripheral production of estrogen?

Distinguishing Ovarian versus Peripheral Hormone Production

Measuring FSH, LH, testosterone, and DHEA-S allows you to differentiate between ovarian and peripheral (adrenal and tissue-level) hormone production by identifying the source and regulatory patterns of sex steroids.

Understanding the Hormone Production Sources

Ovarian Production Indicators

FSH and LH levels directly reflect ovarian function and can reveal whether the ovaries are actively producing hormones or are suppressed. 1

• Elevated FSH (>35 IU/L) and LH (>11 IU/L) indicate ovarian failure, meaning the ovaries are no longer producing significant estrogen, prompting compensatory pituitary hormone increases 2
• LH:FSH ratio >2 suggests polycystic ovary syndrome with ovarian hyperandrogenism, where the ovaries are overproducing androgens 2
• Suppressed FSH and LH indicate adequate estrogen feedback from either ovarian or peripheral sources, or exogenous hormone administration 1

Peripheral (Adrenal and Tissue) Production Indicators

DHEA-S is the most reliable marker of adrenal androgen production, as it is exclusively produced by the adrenal glands. 1

• Elevated DHEA-S (accounting for age and race) indicates adrenal contribution to total androgen pool, which can then be converted peripherally to testosterone and estrogens 1
• DHEA-S levels decline 60% from age 30 to menopause, so age-adjusted interpretation is critical 3
• Normal or low DHEA-S with elevated testosterone suggests ovarian rather than adrenal androgen production 1

Testosterone as a Mixed Indicator

Testosterone measurement reveals combined ovarian and peripheral production, but cannot distinguish sources without additional hormones. 1, 4

• Testosterone is produced by both ovaries and adrenals, and can also be synthesized peripherally from DHEA and androstenedione 1, 4
• Ovarian-peripheral gradients show that ovarian testosterone levels are significantly higher than peripheral levels in 75% of postmenopausal women, confirming ongoing ovarian androgen production 5
• The postmenopausal ovary remains an androgen-secreting organ, with testosterone levels not directly influenced by menopause itself 4

Clinical Algorithm for Source Determination

Step 1: Assess Gonadotropins (FSH/LH)

• If FSH >35 IU/L and LH >11 IU/L: Ovarian failure confirmed; any circulating estrogen is from peripheral conversion of adrenal androgens 2
• If LH:FSH ratio >2: Ovarian hyperandrogenism (PCOS pattern); ovaries are primary androgen source 2
• If FSH and LH are suppressed: Either adequate ovarian function or peripheral estrogen production is providing negative feedback 1

Step 2: Measure DHEA-S for Adrenal Contribution

• Elevated DHEA-S (age-adjusted): Significant adrenal contribution to androgen pool, which undergoes peripheral conversion to testosterone and estrogens 1, 3
• Low DHEA-S with elevated testosterone: Ovarian source is dominant 1
• Both low: Consider adrenal insufficiency or chronic illness 4

Step 3: Interpret Testosterone in Context

• High testosterone + high DHEA-S + normal FSH/LH: Mixed ovarian and adrenal production with peripheral conversion 1, 4
• High testosterone + low DHEA-S + LH:FSH >2: Predominantly ovarian hyperandrogenism 1
• Low testosterone + high FSH: Ovarian failure with inadequate peripheral conversion despite adrenal precursors 4

Critical Pitfalls to Avoid

Timing and Assay Method Matter

Measure FSH and LH on cycle days 3-6 (average of three samples 20 minutes apart) for accurate baseline assessment in premenopausal women. 2

• LC-MS/MS for testosterone measurement is superior to immunoassays, particularly when testosterone levels are low, as direct immunoassays are highly inaccurate 1
• SHBG levels affect free testosterone availability; estrogen therapy increases SHBG by 160%, dramatically reducing bioavailable testosterone despite unchanged total levels 6

Medication Effects

Estrogen replacement therapy suppresses both ovarian and adrenal androgen production through multiple mechanisms. 6

• Oral estrogen decreases testosterone by 42% and DHEA-S by 23% through LH suppression (reducing ovarian production) and possible direct adrenal effects 6
• Aromatase inhibitors in premenopausal women can paradoxically increase ovarian estrogen production by stimulating FSH/LH release, requiring confirmation of ovarian suppression with estradiol measurement 1

Age-Related Considerations

DHEA-S has maximal value in premenopausal women (ages 20-30) and declines steadily thereafter, requiring age-adjusted reference ranges. 1

• Postmenopausal ovaries with stromal hyperplasia can produce significant estradiol, not just androgens, so microscopic ovarian characteristics matter 7
• Peripheral conversion efficiency varies with body weight; higher body weight correlates with increased peripheral estrone production from androgens 7, 5

Practical Integration

The combination of FSH/LH (ovarian function), DHEA-S (adrenal production), and testosterone (combined output) provides a complete picture of hormone source. 1, 2

• In premenopausal women with hyperandrogenism, this panel distinguishes PCOS (ovarian) from adrenal causes 1
• In postmenopausal women on aromatase inhibitors, measuring estradiol with FSH/LH confirms adequate ovarian suppression, as incomplete suppression leads to treatment failure 1
• In women with suspected androgen deficiency, low testosterone with low DHEA-S suggests adrenal insufficiency, while low testosterone with normal DHEA-S suggests ovarian failure or SHBG elevation 4, 6