The associations between the use of any antihypertensive medications, as well as angiotensin II receptor antagonists, and bleeding were evaluated
The associations between the use of any antihypertensive medications, as well as angiotensin II receptor antagonists, and bleeding were evaluated. bleeding/spotting) rates increased over time and were relatively high from cycle 1 to 13 with TX-001HR (56%-73%; placebo 79%; em P /em ? ?0.05 except with 0.25/50 dose). Few vaginal bleeding adverse events (1.0%-4.6% TX-001HR vs 0.7% placebo) were reported and discontinuations due to bleeding were low (0.4%-1.4% vs 0%). Cumulative amenorrhea was significantly more frequent in older ladies, those further using their last menstrual period, and those with lower baseline E2 concentrations (all; em P /em ? ?0.01). Conclusions: All doses of TX-001HR offered endometrial safety and were associated with an improved bleeding profile over time; older age, further last menstrual period, or lower baseline E2 may forecast amenorrhea with TX-001HR. strong class=”kwd-title” Keywords: Darapladib Amenorrhea, Bleeding, Endometrial hyperplasia, Estradiol, Progesterone Estrogens are the pharmacologic treatment of choice for most postmenopausal ladies with moderate to severe vasomotor symptoms (VMS). Unopposed estrogen therapy is definitely, however, well known to be associated with an increased incidence of endometrial malignancy in postmenopausal ladies having a uterus.1 This effect is mitigated by adding a progestogen to estrogen therapy, with progesterone (P4) as one of the more common progestogens used. The REPLENISH trial evaluated TX-001HR (TherapeuticsMD, Boca Raton, FL), a once-daily, oral capsule comprising bioidentical E2 and P4 as active ingredients, biochemically identical to their endogenous counterparts. This is the first time that E2 and P4 have been analyzed collectively and combined in one, oral capsule for the treatment of moderate to severe VMS in postmenopausal ladies having a uterus. One of the main objectives of the REPLENISH trial was to determine whether TX-001HR would guard the endometrium by having a yearly hyperplasia incidence rate of less than 1%, as required by the US Food and Drug Administration (FDA) guidance and much like an untreated populace.2 The efficacy and overall safety of TX-001HR for the treatment of moderate to severe VMS in postmenopausal ladies with an intact uterus were recently reported,3 and the 1?mg E2/100?mg P4 dose (Bijuva) H3FL was approved by the FDA in October 2018 for the treatment of moderate to severe VMS in postmenopausal women.4 We statement here the effect of TX-001HR used daily for 1 year on endometrial safety (Sera), evaluate amenorrhea and bleeding patterns of users, and identify predictors of amenorrhea with its use. METHODS Study design REPLENISH (“type”:”clinical-trial”,”attrs”:”text”:”NCT01942668″,”term_id”:”NCT01942668″NCT01942668) was a phase 3, randomized, double-blind, placebo-controlled, multicenter trial that evaluated TX-001HR in postmenopausal ladies having a uterus. The Darapladib study was conducted in accordance with Good Clinical Practice and the protocol was authorized by an institutional review table; all women offered written educated consent before participation. Study design details have been published elsewhere.3 Ladies with moderate to severe sizzling flushes (7/day time or 50/wk) were included in a VMS substudy and were randomized 1:1:1:1:1 to daily E2/P4 (mg/mg) of 1/100, 0.5/100, 0.5/50, or 0.25/50, or placebo for 12 months. Women not meeting VMS substudy eligibility were randomized 1:1:1:1 to the same active E2/P4 doses only. Women randomized either way could be eligible to be part of the primary security endpoint analysis of endometrial hyperplasia, as explained below.3 Per study protocol, treatments were taken orally at bedtime with food as it has been shown that concomitant food ingestion increases the bioavailability of progesterone.4 Randomization was Darapladib performed at each site using a reproducible, computer-generated, block randomization schedule, and all study investigators and participants were blinded to treatment. Study participants Complete eligibility criteria for study participation were explained previously.3 Women were required to be between the ages of 40 and 65 years, postmenopausal (defined Darapladib as 12 mo of spontaneous amenorrhea, or at least 6 mo of spontaneous amenorrhea with testing serum follicle-stimulating hormone level of 40?mIU/mL, or 6 wk postsurgical bilateral oophorectomy),.