A new solubilized vaginal estradiol in a VagiCap™ for the treatment of vaginal atrophy

Abstract

approved by regulatory agencies worldwide for these indications. The use of HT has declined during the past 12 years in response to the Women’s Health Initiative (WHI) trials. Paradoxically, the use of non-FDAapproved compoundedhormone therapy (CHT) has increased. Recent studies reported that up to 2.5millionUSwomen use non-FDA approved compounded HT containing 17 -estradiol and progesterone annually [1]. The use of compounded HT in the European Union (EU) is not well characterized but is also likely increasing. Non FDA-approved compounded 17 -estradiol and progesterone are often used in varying combinations without the benefit of adequate testing for safety, efficacy and quality of manufacturing. This is a public health issue of great proportion and is often occurringwithout the recognitionofhealth careproviders and their patients as many of them lack knowledge about the differences in testing and oversight of FDA approved and regulated products versus compounded products [1,2]. Up to now, no single product combining natural 17 -estradiol and progesterone has been approved by the US Food and Drug Administration (FDA) or the European Medicines Agency (EMA). The phase 3 REPLENISH trial is underway to study a novel oral formulation of solubilized 17 -estradiol and natural progesterone combined in a single softgel capsule (TX-001HR; TherapeuticsMD) for treating vasomotor symptoms (VMS) in postmenopausal women. The REPLENISH trial evaluates the efficacy and safety of 4 doses of TX-001HR versus placebo for the reduction of moderate to severeVMS frequency and severity at 4 and12weeks andevaluates the endometrial safety of the combinations at 1 year. TX-001HR contains hormones that are molecularly identical to endogenous estradiol and progesterone and is intended as an option for women who prefer bioidentical hormones; further, it does not contain peanut oil, a common allergen. Published data suggest a safer profile of estradiol and natural progesterone compared with HT containing conjugated equine estrogens and progestins [3]. The type of progestogen included in HT may influence the incidence of breast cancer [4]. Observational studies have reported that oral estrogens natural and progesterone has no effect on increasing breast cancer risk as opposed to oral estrogens combined with various progestins [4].