Circulating dihydrotestosterone, testosterone, and free testosterone levels and dihydrotestosterone-to-testosterone ratios in healthy women across the menstrual cycle

Abstract

Objective: To characterize the circulating androgen levels across the menstrual cycle in healthy women using highly sensitive and accurate methods and report sex differences in the relative levels of dihydrotestosterone (DHT) to testosterone (T) levels.

Design: Prospective cohort study.

Setting: Research clinic, academic teaching hospital.

Patient(s): Twenty-one healthy premenopausal women, aged 19-40 years, with regular menstrual cycles.

Intervention(s): Not applicable.

Main outcome measure(s): Serum total T and DHT levels measured using liquid chromatography-tandem mass spectrometry, free T levels measured using a standardized equilibrium dialysis method coupled with measurement of the T levels in the dialysate using liquid chromatography-tandem mass spectrometry, and comparison of the DHT-to-T ratio between healthy women and age-matched healthy men.

Result(s): The serum total and free T levels increased across the follicular phase and peaked at midcycle (total T, 43.6 ± 16.2 ng/dL; free T, 15.6 ± 11.9 pg/mL) and gradually declined in the luteal phase. The DHT level did not significantly change across the menstrual cycle. The DHT-to-T ratios were 1:4 and 1:13 in women and men, respectively.

Conclusion(s): In healthy premenopausal women, the total and free T levels varied significantly across the menstrual cycle, whereas the DHT levels did not change; the peak total and free T levels in the midcycle period were higher than previously reported, underscoring the importance of establishing menstrual phase-specific reference ranges to avoid misdiagnosis of hyperandrogenism. Women have significantly higher DHT levels relative to total T than men; the significance of this sex difference in the DHT-to-T ratio needs further investigation.

Keywords: Testosterone; dihydrotestosterone; equilibrium dialysis; liquid chromatography-tandem mass spectrometry; menstrual cycle.