Sex differences in serum levels of 5α-androstane-3β, 17β-diol, and androstenediol in the young adults: A liquid chromatography-tandem mass spectrometry study

Animal experiments have consistently shown that estrogen receptor beta (ER beta)-selective ligands have antidepressant and anxiolytic effects. In humans, endogenous ligands for ER beta include 5 alpha-androstane-3 beta, 17 beta-diol (3 beta Adiol) and androstenediol (Delta 5-diol). We determined, for the first time, the exact serum levels of 3 beta Adiol and Delta 5-diol in young healthy volunteers using liquid chromatography-tandem mass spectrometry (LC-MS/MS). We investigated the effect of the menstrual cycle on the levels of these steroids in women; then, we performed a gender comparison. Blood samples were collected from 48 subjects: 23 women (mean age = 28.4 +/- 7.8 years) and 25 men (mean age = 31.4 +/- 7.8 years). We collected the blood samples of women at three time-points in the menstrual cycle: the early follicular phase, ovulatory or mid-cycle phase, and mid-luteal phase. A total of 92 blood samples were analyzed using LC-MS/MS. The levels of two well-studied steroids, namely dehydroepiandrosterone (DHEA) and 17 beta-estradiol (E2), were simultaneously measured. Depression rating scale (Hamilton Rating Scale for Depression, Beck Depression Inventory-II and Quick Inventory of Depressive Symptomatology) scores were also recorded at the time of blood sampling. Significant differences in the levels of 3 beta Adiol and E2 and in the depression rating scale scores were observed over the duration of the menstrual cycle of the women. The levels of 3 beta Adiol and Delta 5-diol were significantly lower in women than in men. E2 levels were higher in women than in men, and DHEA levels did not differ significantly between men and women. Further, women had higher scores than men on the Hamilton Rating Scale for Depression. Sex differences in depressive symptoms can be explained by 3 beta Adiol and Delta 5-diol levels, and the effect of the menstrual cycle on mood can be explained by 3 beta Adiol and E2 levels, not by Delta 5-diol level.

Automated summary

The study found significant differences in 3 beta Adiol and E2 levels, as well as depression scores, over the menstrual cycle in women. Women had lower levels of 3 beta Adiol and Delta 5-diol compared to men, while E2 levels were higher in women. DHEA levels did not differ significantly between genders.