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. 2012 Jun;19(6):650-7.
doi: 10.1097/gme.0b013e31823df577.

Androstenediol complements estrogenic bioactivity during the menopausal transition

Bill L Lasley  1 , Jiangang Chen, Frank Z Stanczyk, Samar R El Khoudary, Nancy A Gee, Sybil Crawford, Daniel S McConnell
Affiliations

Androstenediol complements estrogenic bioactivity during the menopausal transition

Bill L Lasley et al. Menopause. 2012 Jun.

Abstract

Objective: The perimenopausal increase in circulating dehydroepiandrosterone sulfate (DHEAS) levels during the menopausal transition (MT) is accompanied by other adrenal steroids that have the potential to alter estrogen/androgen balance and explain the wide interwoman range of estrogen-related symptoms experienced during the MT.

Methods: Annual serum samples from the Study of Women's Health Across the Nation, which had previously been analyzed for immunoreactive estradiol (E2), testosterone, DHEAS, and sex hormone-binding globulin, were selected based on DHEAS concentration and analyzed for immunoreactive and bioactive estrogens and androgens, including immunoreactive androstenedione, dehydroepiandrosterone, and 5-androstene-3β,17β-diol (androstenediol [Adiol]).

Results: A two-fold increase in circulating androstenedione and testosterone was found to rise in parallel with the rise in circulating DHEAS, whereas dehydroepiandrosterone and Adiol concentrations rose seven- to eight-fold. Circulating Adiol, which has both androgenic and estrogenic biological activity, was significantly associated (P < 0.02) with circulating estrogen bioactivity only when E2 concentrations were low and Adiol levels were high.

Conclusions: The wide range of circulating levels of Adiol and its contribution to total circulating estrogenicity during the MT is consistent with the observed interwoman difference in symptoms at this time. Therefore, we conclude that Adiol contributes to circulating estrogenicity when E2 production falls at menopause and may contribute significantly to the endocrine changes experienced by midlife women.

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Conflict of interest statement

The author have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Selection of Samples. Box plot display depicting the distribution of serum samples selected for hormone analysis. The selection was based on serum DHEAS concentration chosen from the full SWAN Sample cohort.
Figure 2
Figure 2
The dose-response curves and molecular structures for estradiol (E2), androstenediol (ADIOL), dehydroepiandrosterone (DHEA) and testosterone (T) using a stably transfected cell line. Relative biological activity of each steroid was assessed using a cell-base signal transduction assay for estrogen receptor-alpha ligand load (ERLL). The concentration for each steroid is shown on the abscissa (M) and the signal transduction strength is shown on the ordinate in relative light units (RLUs).
Figure 3
Figure 3. Linear regression analysis for DHEAS, AR ligands and ER ligands
Upper Panel: Linear regression analysis of log transforms of circulating concentrations of testosterone (T, closed circles), androstenedione (Adione, closed squares) and androstenediol (Adiol, open triangles) versus the log transform of dehydroepiandrosterone sulfate (DHEAS). Compared to T, both Adione and Adiol are more strongly related to DHEAS. Lower panel: The log transform of all circulating Adiol concentrations are highly associated with the estimate of circulating androgenicity (open circles) while there is no relationship between the log transform of Adiol and circulating estrogenicity when all Adiol measurements are included.
See this image and copyright information in PMC

References

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