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 17β-estradiol (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.

KEYWORDS:

• Amenorrhea
• endometrial safety
• estradiol
• menopause
• progesterone
• vasomotor symptoms

Article Highlights

• A combined, bioidentical, oral, 17β-estradiol (E2; 1 mg)/progesterone (P4; 100 mg) capsule was approved for the treatment of moderate to severe vasomotor symptoms in postmenopausal women with a uterus

• This E2/P4 formulation is the first time the two bioidentical hormones have been combined in one capsule due to biochemical challenges

• The REPLENISH study found that combined E2/P4 statistically and clinically significantly improved menopausal vasomotor symptoms

• Continuous use of P4 contained in the TX-001HR formulation was shown to protect the endometrium from estradiol stimulation in the randomized, controlled, phase 3, REPLENISH trial; these data cannot be transferred to other E2 + P4 products

• Combined E2/P4 (TX-001HR) had a good uterine bleeding profile that improved over time

• Various doses of E2/P4 significantly improved quality of life and sleep outcomes in postmenopausal women

Acknowledgments

The authors appreciate the medical writing assistance provided by Elizabeth Jennison, MD and Kathleen Ohleth, PhD of Precise Publications, LLC.

Declaration of interest

DF Archer serves as a consultant for Abbvie, Actavis, Agile Therapeutics, Bayer Healthcare, Endoceutics, Exeltis, InnovaGyn, Merck, Pfizer, Radius Health, Sermonix, Shionogi, Teva Women’s Healthcare, and TherapeuticsMD; and has received research support from Actavis, Bayer Healthcare, Endoceutics, Glenmark, Merck, Radius Health, Shionogi, and TherapeuticsMD. B Bernick and S Mirkin are employees of TherapeuticsMD with stock/stock options. B Bernick is also a Board member of TherapeuticsMD.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

The authors have disclosed to the journal editor that a scientific accuracy check of the paper was carried out by the sponsor.

Additional information

Funding

TherapeuticsMD (Boca Raton, Florida) provided support for medical writing assistance of this manuscript.