Histological and Gene Expression Analysis of the Effects of Menopause Status and Hormone Therapy on the Vaginal Introitus and Labia Majora.

BACKGROUND: The study aimed to determine the effect of menopausal status and hormone therapy on the introitus and labia majora at the levels of histology and gene expression. METHODS: Three cohorts of 10 women each (pre-menopause, post-menopause and post-menopause + hormone therapy) were selected based on the presentation of clinical atrophy and vaginal pH. Biopsies were obtained from the introitus (fourchette) and labia majora and processed for histology and gene expression analyses with microarrays. Other data collected included self-assessed symptoms, serum estradiol, testosterone, serum hormone binding globulin and the pH of the vagina and labia majora. RESULTS: The introitus appears exquisitely sensitive to hormone status. Dramatic changes were observed in histology including a thinning of the epithelium in post-menopausal subjects with vaginal atrophy. Furthermore, there was differential expression of many genes that may contribute to tissue remodeling in the atrophic introitus. Levels of expression of genes associated with wound healing, angiogenesis, cell migration/locomotion, dermal structure, apoptosis, inflammation, epithelial cell differentiation, fatty acid, carbohydrate and steroid metabolism were significantly different in the cohort exhibiting atrophy of the introitus. While changes were also observed at the labia, that site was considerably less sensitive to hormone status. The gene expression changes observed at the introitus in this study were very similar to those reported previously in the atrophic vagina providing further evidence that these changes are associated with atrophy. CONCLUSIONS: The histological and gene expression changes occurring within the introitus after menopause may contribute to the constellation of symptoms that constitute the genitourinary syndrome of menopause.

Emollients on the genital area.

Emollients are known to lubricate, moisturize and soothe the skin. Prior to their incorporation into feminine hygiene pads, thorough premarket toxicological testing is conducted to evaluate their safety and effectiveness via in-use clinical settings. Product testing has been conducted on various body sites proven previously to be valid and reliable, such as the arm and popliteal fossa and, more recently, the genital area. Several clinical studies have confirmed the safety and efficacy of emollient-containing feminine hygiene products, which have also been shown to provide dermatological benefits in the genital area.

The vulva is relatively insensitive to menses-induced irritation.

Skin patch testing of menses and venous blood on the vulva (labia majora) and the upper arm was performed to assess the potential contribution of these biological fluids to vulvar irritation during menstruation. After 24 and 48 hours of occlusive exposure, the skin of the labia majora was relatively unaffected by these fluids compared to the skin of the upper arm: no significant irritation was observed on the labia at either exposure time, but discernible irritation was elicited on the upper arm after 48 hours of exposure. Pre-treatment of the upper arm with a petrolatum-based emollient attenuated the upper arm response. Semi-occlusive conditions also reduced the degree of upper-arm irritation elicited test materials and an irritant control, sodium lauryl sulfate. The relative insensitivity of the vulva to irritation by menses or blood was not predictable a priori because some irritants elicit heightened responses on the vulva relative to the arm (3). These results suggest that the vulva (labia majora) may be adapted to be less sensitive to menses-induced skin irritation than other anatomical sites.