Introduction to INTRAROSA, an Endoceutics Discovery
Data developed by Endoceutics has demonstrated the presence of another very important, but previously unrecognized, source of sex steroids in women, dehydroepiandrosterone (DHEA), a compound inactive in itself but the precursor of all intracellular sex steroids.
In fact, after menopause, a time when the secretion of estrogens by the ovaries stops, the only source of estrogens and androgens becomes DHEA which is transformed intracellularly into estrogens and androgens in peripheral target tissues without biologically significant release of active estrogens or androgens in the blood. This achievement is due to the intracellular inactivation of the estrogens and androgens made from DHEA in the same cells where they are synthesized.
And the serum concentrations are highly variable between women, with levels ranging from barely detectable in some women to relatively high values or concentrations, similar to those seen before menopause, in other women.
The cessation of estrogen secretion by the ovaries at menopause is a normal phenomenon present in all women. Consequently, the biologically inactive concentration of estradiol in the circulation observed after menopause cannot explain why some women have menopausal symptoms, while others do not suffer from such symptoms. In fact, cessation of estrogen secretion by the ovaries is the same in all women and the serum concentration of estradiol is very low and biologically inactive in all women.
Consequently, since DHEA is the exclusive source of sex steroids after menopause, women with high serum DHEA can have no or minimal menopausal symptoms, while women with low DHEA are more likely to suffer from menopausal symptoms -- the lack of DHEA is thus the cause of the symptoms of menopause.
DHEA is secreted mostly by the adrenal glands into the general circulation which distribute the inactive precursor molecule to all tissues where it is locally transformed intracellularly into precise and very small quantities of androgens and estrogens which permit a local control of cellular activity according to local needs. Since estrogens and androgens made intracellularly from DHEA are degraded locally, only the inactive degradation products are released in the blood for elimination by the liver and kidneys.
Endoceutics has developed a non-estrogenic treatment for vulvovaginal atrophy. This treatment uses prasterone (DHEA), a compound without intrinsic estrogenic or androgenic activity which is transformed intracellularly into androgens and estrogens only in the cells and vaginal layers physiologically in need of these sex steroids. This innovative treatment provides a replacement for the local deficiency in sex steroids with no significant increase in circulating estrogens or androgens.
In addition, positive effects have been observed on the four domains of sexual dysfunction, namely desire, arousal, orgasm and pleasure, an effect secondary to local androgen formation and not found with estrogens. These observations are under evaluation by Endoceutics.
Pre-clinical studies have demonstrated that prasterone, through its local conversion into both estrogens and androgens, affects all three layers of the vaginal wall, thus permitting beneficial effects on vulvovaginal atrophy and possibly sexual dysfunction (to be confirmed in future clinical trials).