Uterine bleeding with hormone therapies in menopausal women: a systematic review.

Uterine bleeding is a common reason why women discontinue menopausal hormone therapy (HT). This systematic review compared bleeding profiles reported in studies for continuous-combined HT approved in North America and Europe for moderate to severe vasomotor symptoms in postmenopausal women with a uterus. Non-head-to-head studies showed that uterine bleeding varies by formulation and administration route, with oral having a better bleeding profile than transdermal formulations.

Endometrial safety and bleeding profile of a 17β-estradiol/progesterone oral softgel capsule (TX-001HR).

Objective: The aim of the study was to evaluate the effect of a single-capsule 17β-estradiol/progesterone (E2/P4), TX-001HR, on endometrial safety, to report on amenorrhea and bleeding patterns of users, and to identify predictors of amenorrhea.

Methods: The REPLENISH trial (NCT01942668) evaluated use of TX-001HR in menopausal women (40-65 y) with vasomotor symptoms (VMS) and a uterus. Women were randomized to daily E2/P4 (mg/mg: 1/100, 0.

Physical characteristics and properties of estradiol softgel vaginal inserts.

Objective: TX-004HR is a low-dose estradiol (E2) softgel vaginal insert designed to be rapidly dissolving and mucoadhesive. This report describes the physical attributes and pharmacokinetic parameters of the softgel vaginal insert evaluated for the treatment of moderate to severe dyspareunia due to menopausal vulvar and vaginal atrophy.

Methods: In vitro dissolution studies with 25-μg E2 inserts were performed and media samples were analyzed for E2 by high-performance liquid chromatography.

Estradiol and progesterone bioavailability for moderate to severe vasomotor symptom treatment and endometrial protection with the continuous-combined regimen of TX-001HR (oral estradiol and progesterone capsules).

Objective: In the REPLENISH trial, women receiving TX-001HR-an oral, softgel capsule, combining 17β-estradiol (E2) and progesterone (E2 mg/P4 mg 1/100, 0.5/100), had significantly improved vasomotor symptoms, while having their endometrium protected from hyperplasia. The objective here was to describe P4 levels sufficient to counteract the potential endometrial effects of 1 or 0.

Estradiol vaginal inserts (4 µg and 10 µg) for treating moderate to severe vulvar and vaginal atrophy: a review of phase 3 safety, efficacy and pharmacokinetic data.

Objective: To review safety, efficacy and pharmacokinetic (PK) data from the phase 3 REJOICE trial, which evaluated a 17β-estradiol (E2) softgel vaginal insert approved in 2018 for moderate to severe dyspareunia associated with menopausal vulvar and vaginal atrophy (VVA).

Methods: REJOICE (Clinicaltrials.gov: NCT02253173) was a randomized, double-blind, placebo-controlled trial in which women with moderate to severe dyspareunia due to menopausal VVA received 4 µg, 10 µg or 25 µg of an E2 vaginal insert or placebo for 12 weeks.

A 17β-Estradiol-Progesterone Oral Capsule for Vasomotor Symptoms in Postmenopausal Women: A Randomized Controlled Trial.

Objective: To evaluate efficacy, endometrial safety, and overall safety of a single-capsule 17β-estradiol-progesterone (TX-001HR) for treating menopausal moderate-to-severe vasomotor symptoms.

Methods: REPLENISH was a phase 3, 12-month, randomized, double-blind, placebo-controlled, multicenter trial. Women (aged 40-65 years) with vasomotor symptoms and a uterus were randomized to daily estradiol (mg)-progesterone (mg) (1/100, 0.

Tissue selective estrogen complex (TSEC): a review.

Objective: This review describes historical development of selective estrogen receptor modulators (SERMs) and their combination with estrogens, termed a tissue selective estrogen complex (TSEC), and considers the potential for future TSEC development.

Methods: This narrative review is based on literature identified on PubMed and the TSEC research and development experience of the authors.

Results: SERMs have estrogenic and antiestrogenic effects in various tissues; however, no single agent has achieved an optimal balance of agonist and antagonist effects for the treatment of menopausal symptoms.

Initial investigation into the optimal dose ratio of conjugated estrogens and bazedoxifene: a double-blind, randomized, placebo-controlled phase 2 dose-finding study.

Objective: The aim of the study was to explore dose-related endometrial effects of conjugated estrogens/bazedoxifene (CE/BZA).

Methods: In this randomized, double-blind, phase 2 study, 408 nonhysterectomized, symptomatic (with hot flushes [HFs]) postmenopausal women received ≥1 dose of CE 0.3 or 0.

Menopausal hormone therapy for primary prevention: why the USPSTF is wrong.

The US Preventive Services Task Force (USPSTF) Draft Recommendation statement on Menopausal Hormone Therapy: Primary Prevention for Chronic Diseases, released in May 2017, perpetuates a major disconnect between the primary population affected, women within roughly 10 years of menopause, and the data cited. Furthermore, major elements of the evidence relied upon have been misinterpreted or misstated, particularly in regard to coronary heart disease and breast cancer, for which there is no statistically significant evidence of harm. As currently drafted, the recommendations reiterate the USPSTF statements of 2012, 2005 and 2002, and will perpetuate egregious harm to the public health.

Safety and benefit considerations for menopausal hormone therapy.

While benefits and risks of hormone therapy (HT) have been shown in rigorous randomized, controlled trials, clinical use and further study have discovered effects of age, time of HT initiation, and differential effects of various regimens and administration routes on its safety profile. Areas covered: The safety of HT with regard to cardiovascular disease, thrombosis, the endometrium, the breast, and cognition was reviewed. Differential safety effects of estradiol versus conjugated equine estrogens, and progesterone versus synthetic progestins are reported.

Characteristics of Paraspinal Muscle Spindle Response to Mechanically Assisted Spinal Manipulation: A Preliminary Report.

Objectives: The purpose of this preliminary study is to determine muscle spindle response characteristics related to the use of 2 solenoid powered clinical mechanically assisted manipulation (MAM) devices.

Methods: L6 muscle spindle afferents with receptive fields in paraspinal muscles were isolated in 6 cats. Neural recordings were made during L7 MAM thrusts using the Activator V (Activator Methods Int.

A vaginal estradiol softgel capsule, TX-004HR, has negligible to very low systemic absorption of estradiol: Efficacy and pharmacokinetic data review.

This paper reviews the efficacy, safety, and systemic absorption of estradiol with TX-004HR, an investigational, low-dose 17β-estradiol vaginal softgel capsule, designed to treat vulvar and vaginal atrophy (VVA) in postmenopausal women, with an improved user experience. In phase 2 (NCT02449902) and phase 3 REJOICE (NCT02253173) studies, TX-004HR significantly improved the proportions of vaginal superficial and parabasal cells and vaginal pH, and in the phase 3 study decreased the severity of dyspareunia, vaginal dryness, and vulvar and/or vaginal itching or irritation. In two randomized, phase 1 trials, estradiol C and AUC were significantly lower with 10μg and 25μg TX-004HR than with the same doses of an approved vaginal estradiol tablet.

Consistency of Effect with a Low-Dose, Estradiol Vaginal Capsule (TX-004HR): Evaluating Improvement in Vaginal Physiology and Moderate-to-Severe Dyspareunia in Subgroups of Postmenopausal Women.

Background: The 12-week, randomized, double-blind, placebo-controlled, multicenter, phase 3 REJOICE trial demonstrated that TX-004HR, an investigational, applicator-free, low-dose vaginal softgel capsule containing solubilized 17β-estradiol, effectively and rapidly treats symptoms of vulvar and vaginal atrophy (VVA) with negligible to very low systemic absorption. The aim of this analysis was to assess whether the efficacy of TX-004HR varies with age, body mass index (BMI), uterine status, pregnancy status, and vaginal delivery.

Methods: The REJOICE trial evaluated the efficacy of 4-, 10-, and 25-μg doses of TX-004HR in postmenopausal women (40-75 years) with VVA and a self-identified most bothersome symptom of moderate-to-severe dyspareunia.

The REJOICE trial: a phase 3 randomized, controlled trial evaluating the safety and efficacy of a novel vaginal estradiol soft-gel capsule for symptomatic vulvar and vaginal atrophy.

Objective: To evaluate the safety and efficacy of TX-004HR vaginal estradiol soft-gel capsules for moderate-to-severe dyspareunia associated with postmenopausal vulvar and vaginal atrophy.

Methods: In this randomized, double-blind, placebo-controlled, phase 3 study, postmenopausal women with a self-identified most bothersome symptom of dyspareunia received 4, 10, or 25 μg TX-004HR or placebo for 12 weeks. Four co-primary efficacy endpoints were change from baseline to week 12 in percentages of superficial and parabasal cells, vaginal pH, and severity of dyspareunia.

Back to the future: Hormone replacement therapy as part of a prevention strategy for women at the onset of menopause.

In the late 1980s, several observational studies and meta-analyses suggested that hormone replacement therapy (HRT) was beneficial for prevention of osteoporosis, coronary heart disease, dementia and decreased all-cause mortality. In 1992, the American College of Physicians recommended HRT for prevention of coronary disease. In the late 1990s and early 2000s, several randomized trials in older women suggested coronary harm and that the risks, including breast cancer, outweighed any benefit.