Vaginal rings for menopausal symptom relief

Abstract

The vagina is an alternative delivery site of sex steroids for menopausal women. New ring technology provides continuous and consistent delivery of steroids for up to 3 months. Rings rest on the pelvic floor muscles in a nearly horizontal position and are usually imperceptible. Steroid is delivered directly into the systemic circulation which may result in less alteration of coagulation/fibrinolysis pathways as seen with transdermal hormone therapy. Fewer adverse effects are noted when progesterone is applied vaginally, possibly due to lower serum levels of metabolites such as alloprenanolone. Women often switch to a ring for the longer dosing interval but also appreciate the reduced messiness. Over 5700 healthy US women who evaluated an unmedicated ring as a drug delivery platform found it very acceptable independent of age or prior use of barrier contraceptives. Marketed rings in the US include: (i) a ring for systemic and vaginal menopausal therapy that provides average serum estradiol levels of 40.6 pg/mL for the 0.05 mg and 76 pg/mL for the 0.1 mg dose; (ii) a ring for urogenital menopausal symptoms only that minimally elevates serum estradiol, usually within the menopausal range, treating atrophic vaginitis and urethritis; and (iii) a ring labelled for contraception that provides ethinyl estradiol 15 microg and etonogestrel 120 microg appropriate for nonsmoking perimenopausal women. A ring for combination hormone therapy and another releasing progesterone for contraception in lactating women have been reported in the literature, but are not yet available commercially. These may offer future options for hormone therapy. Women with a uterus receiving estrogen, even in low doses, should be given progestogen to prevent endometrial hyperplasia or carcinoma. Even women who have had an endometrial ablation are likely to have some endometrial tissue remaining since long-term amenorrhoea is uncommon. Since no marketed combination ring product is available, other forms of progestogen are necessary. Vaginal rings offer a novel approach to menopausal hormone therapy producing consistent serum levels sustained for up to 3 months per unit dose with lower adverse effects than other vaginal products and high acceptability among users.