Intravaginal Administration of Conjugated Estrogens in Premenopausal and Postmenopausal Women

Abstract

Daily doses of 0.625 mg of conjugated estrogens were administered intravaginally for 14 days to 12 postmenopausal women (six with highly atrophic and six with slightly atrophic vaginal mucosa), resulting in vaginal mucosae similar to those found in premenopausal women in all 12 subjects. In a second experiment, serum estrogens, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were determined before and hourly for six hours after a single intravaginal dose of 0.625 mg of conjugated estrogens was given to five postmenopausal women and to five premenopausal women on cycle days 6-8. Serum levels of unconjugated immunoreactive estrogens and total estrone increased rapidly in four of five postmenopausal women. Luteal phase values were found after only two hours, but there were no effects on serum FSH and LH. One of the postmenopausal women who had an unatrophied vaginal mucosa, showed a considerable lower resorption of estrogens. There were no significant changes in the serum estrogen levels of the premenopausal women. Thus, we conclude that daily vaginal administration of 0.625 mg of conjugated estrogens for 14 days is sufficient to restore an atrophic vaginal mucosa to a premenopausal condition. Furthermore, the condition of the vaginal mucosa seems to influence the resorption, thus indicating an inbuilt mechanism of protection against overdosage of intravaginally applied estrogens.

Topical KGF treatment as a therapeutic strategy for vaginal atrophy in a model of ovariectomized mice

“…Up to now, no consensus has been achieved with regard to appropriate therapy: HRT should be given to women with menopausal complaints to meet their needs, taking into account their individual risk profile and the overall therapeutic objectives. Intravaginal oestrogen formulations have been introduced to avoid systemic exposure to oestrogens and are now preferred in women with no other menopausal symptoms requiring systemic treatment . However, the safety of local oestrogen treatment has been discussed, as data about the potential increase in serum levels of oestradiol with the use of vaginal tablets and creams are controversial.…”

Pelvic floor sex steroid hormone receptors, distribution and expression in pre‐ and postmenopausal stress urinary incontinent women

“…Para‐urethral punch biopsies, 6 mm in diameter and 10 mm in depth, were obtained from the SUI women during the TVT procedure, as described earlier (13). Corresponding biopsies were collected from the control patients during gynecological examination (1), or the respective operation (hysterectomy (5), laparoscopic operation of benign ovarian cysts (3), dilatation and curettage (2)).…”

“…The patients and controls were selected as above. The controls underwent hysterectomy (5), laparoscopic operation of ovarian cysts (3), and dilatation and curettage (2). See Table II regarding age, parity and hormonal use.…”

“…Since these events coincide, many SUI patients are treated with, at the least, low dose locally administered estrogens. A beneficial effect of estrogens on vaginal epithelial atrophy after menopause has been well established, but the effects and their mechanisms concerning SUI are unclear (2). A few clinical and experimental studies have been performed on this subject showing beneficial effects of estrogen (3, 4).…”

Hormonal treatment of vulvar vaginal atrophy (VVA): Are there options to reduce or avoid systemic adverse effects and risks?

“…The observation that serum levels of other sex hormones and their binding proteins were not influenced can lead to the conclusion that there are no systemic actions at all, since especially the hepatic production of binding proteins is very sensitive to any estrogen effect. The decrease in E3-level after repeated vaginal application presumably is caused because of increased local metabolism within epithelial maturation, improved during the initial therapy: E3 absorption via a well-proliferated vaginal epithelium is markedly lower than that via an atrophic one [54,[84][85][86]. Derived from those pharmacokinetic studies it was suggested, that the use of 0.03-E3/L is safe without risk of endometrial or other systemic effects and may be considered for patients with a history of breast cancer and treated with aromatase inhibitors [84,87].…”