A combined, bioidentical, oral, 17β-estradiol and progesterone capsule for the treatment of moderate to severe vasomotor symptoms due to menopause

Abstract

Introduction: Many women seek treatment to alleviate menopausal vasomotor symptoms (VMS). Numerous women use combination compounded hormone therapy (CHT) to achieve the benefits of estrogen/progesterone for endometrial protection. TX-001HR is a combination of bioidentical 17βestradiol (E2) and progesterone (P4) in a single capsule designed for continuous daily use to treat moderate to severe VMS. Areas covered: This drug profile describes the efficacy and safety of 4 doses of this E2/P4 (mg/mg: 1/ 100, 0.5/100, 0.5/50, 0.25/50) for treating moderate to severe VMS in menopausal woman with a uterus. Expert opinion: In REPLENISH (NCT01942668), the two highest doses of TX-001HR significantly reduced VMS frequency and severity at 4 and 12 weeks versus placebo (co-primary endpoints); all doses met the primary endpoint of endometrial safety. Rates of amenorrhea were high and improved over time; the Menopause Quality of Life and Medical Outcomes Study-Sleep instruments improved with E2/P4. TX-001HR was well tolerated and had no clinically significant impact on vital signs, metabolic or coagulation parameters, or breast safety. The combination bioidentical E2/P4 capsule (1 mg/100 mg dose was FDA-approved as Bijuva in October 2018) may provide a safe, effective, rigorously studied alternative for women with a uterus who prefer CHT for relief of VMS.

Position Statement by Experts of the Polish Menopause and Andropause Society on menopausal hormone therapy with an oral combination drug containing oestradiol 1 mg and progesterone 100 mg

“…In this context, great hopes are being pinned on the first approved oral combination drug for MHT called Bijuva®, containing a low dose of 17β-oestradiol and micronised progesterone. Both compounds, which are the active substances of this drug, are molecularly and chemically identical to the endogenous hormones oestradiol and progesterone [13].…”

“…In the REPLENISH trial, a total of 1,835 female subjects were randomised to one of four groups receiving combined E2/P4 products containing different doses of hormones (1 mg E2/100 mg P4, 0.5 mg E2/100 mg P4, 0.5 mg E2/50 mg P4, 0.25 mg E2/50 mg P4) or placebo [14]. The results of the REPLENISH trial were presented in three key publications [14][15][16] and in approximately a dozen other papers containing post-hoc analyses of the trial's outcomes [10,13,[17][18][19][20][21][22][23][24][25] This study presents the conclusions of the REPLENISH trial regarding exclusively the subjects who were treated with the product approved as Bijuva®, i.e. oestradiol 1 mg + progesterone 100 mg (E2/P4-1/100), focusing on the pharmacokinetic characteristics, clinical efficacy, and safety profile of the drug.…”

Postmenopausal Hormone Therapy—Local and Systemic: A Pharmacologic Perspective

“…32 A recent study showed 1 year of combined 17 β-estradiol plus micronized progesterone resulted in similar rates of abnormal mammograms as placebo (3.7% versus 3.1%). 33 Other Cancers. Eighteen years of follow-up from the WHI showed similar total cancer mortality rates in the pooled intervention group (8.2%) and the placebo (8.0%): HR, 1.03; 95%CI, 0.95-1.12.…”

“…At the end of the first year of the WHI study, the incidence of abnormal mammograms was 9.4% in women taking conjugated equine estrogen/MPA versus 5.4% for placebo 32 . A recent study showed 1 year of combined 17 β‐estradiol plus micronized progesterone resulted in similar rates of abnormal mammograms as placebo (3.7% versus 3.1%) 33 …”

Bioidentical Oral 17β-Estradiol and Progesterone for the Treatment of Moderate to Severe Vasomotor Symptoms of Menopause

“…4 In addition to GSM, vasomotor symptoms (VMS) such as hot flashes and night sweats are experienced by 50% to 80% of menopausal women. 5 Therefore, a need exists for effective treatment of menopausal symptoms whether it be short-term for VMS or longer term for GSM.…”