Molecular mass: 288.424 g/mol PubChem compound: 5881
Prasterone i.e. dehydroepiandrosterone (DHEA), biochemically and biologically identical to the endogenous human DHEA, is a precursor steroid which is inactive by itself and it is converted into oestrogens and androgens. Prasterone is thus different from the oestrogens preparations since it delivers also androgen metabolites.
An oestrogen-mediated increase in the number of superficial and intermediate cells and decrease in the number of parabasal cells in the vaginal mucosa is noted. In addition, the vaginal pH decreased towards the normal range, thus facilitating the growth of the normal bacterial flora.
Prasterone administered in the vagina is an inactive precursor that enters the vaginal cells and is converted intracellularly into cell-specific small amounts of both oestrogens and androgens depending upon the level of enzymes expressed in each cell type. The beneficial effects on the symptoms and signs of vulvar and vaginal atrophy are exerted through activation of the vaginal oestrogen and androgen receptors.
In a study conducted in postmenopausal women, administration of the prasterone pessary once daily for 7 days resulted in a mean prasterone Cmax and area under the curve from 0 to 24 hours (AUC0-24) at day 7 of 4.4 ng/mL and 56.2 ng h/mL, respectively, which were significantly higher than those in the group treated with placebo (Table; Figure). The Cmax and AUC0-24 of the metabolites testosterone and estradiol were also slightly higher in women treated with the prasterone pessary compared to those receiving placebo but all remained within normal values of postmenopausal women (<10 pg estradiol/mL; <0.26 ng testosterone/mL) as measured by validated mass spectrometry-based assays for both the study samples and reference values.
Cmax and AUC0-24 of Prasterone, Testosterone, and Estradiol on Day 7 Following Daily Administration of Placebo or Prasterone (mean ± S.D.):
| Placebo (N=9) | Prasterone (N=10) | ||
|---|---|---|---|
| Prasterone | Cmax (ng/ml) | 1.60 (±0.95) | 4.42 (±1.49) |
| AUC0-24 (ng⋅h/ml) | 24.82 (±14.31) | 56.17 (±28.27) | |
| Testosterone | Cmax (ng/ml) | 0.12 (±0.04)1 | 0.15 (±0.05) |
| AUC0-24 (ng⋅h/ml) | 2.58 (±0.94)1 | 2.79 (±0.94) | |
| Estradiol | Cmax (pg/ml) | 3.33 (±1.31) | 5.04 (±2.68) |
| AUC0-24 (pg⋅h/ml) | 66.49 (±20.70) | 96.93 (±52.06) | |
1 N=8
Figure 1. Serum Concentrations of Prasterone (A), Testosterone (B), and Estradiol (C) Measured Over a 24h Period on Day 7 Following Daily Administration of Placebo or Prasterone (mean ± S.D.):
The distribution of intravaginal (exogenous) prasterone is mainly local but some increase in systemic exposure is observed especially for the metabolites but within normal values.
Exogenous prasterone is metabolized in the same manner as endogenous prasterone. Systemic metabolism has not been studied in this application.
Systemic elimination has not been studied specifically for this application.
Prasterone was not mutagenic or clastogenic in a standard battery of in vitro and in vivo studies.
Carcinogenic and reproductive and development toxicity studies were not performed.
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