Oral bioidentical combo improved quality of life, vasomotor symptoms

An oral estradiol/ progesterone formulation significantly improved menopause-related quality of life, compared with placebo, for up to one year after beginning treatment, according to a new study.

If approved, the new formulation “may be an option for the estimated millions of women currently using less regulated and unapproved compounded bioidentical hormone therapy.

Patients receiving the combination therapy, termed TX-001HR, experienced a significant improvement in quality of life, compared with placebo and compared with baseline, at all study points.

Using the menopause-Specific Quality of Life questionnaire (MENQOL), it was found that women taking the combination therapy saw reduction in the vasomotor domain of MENQOL within 12 weeks of beginning the study. The significant symptomatic improvement persisted to the full year that patients were followed.

For the patients with particularly bothersome vasomotor symptoms, vasomotor domains scores ranged from 6.9 to 7.2 at baseline and were 2.8-3.6 with TX001HR and 4.4 with placebo at month 12.

During a top abstract session at the annual meeting of the North American Menopause Society, the TX-001HR combines the physiologic sex hormones 17-beta estradiol and progesterone (E2/P4) into a single oral soft-gel.

The phase 3 randomized, double-blind, placebocontrolled REPLENISH trial explored the safety and efficacy of one of four dose combinations of E2/P4. A total of 1,833 patients were randomized to receive E2/P4 in doses of 1.0/100 mg, 0.5/100 mg, 0.5/50 mg, or 0.25/50 mg, or to receive placebo.

An approximately equal number of patients were allocated to each study arm, except that 151 patients were allocated to receive placebo.

The MENQOL is structured so that the 29 items in the symptom inventory are grouped into four domains: vasomotor, psychosocial, physical and sexual. Significant reductions were seen at 12 weeks for all patients in overall MENQOL scores and for the four domains.

The REPLENISH investigators also performed a separate analysis of data from the subset of patients who had moderate to severe vasomotor symptoms (VMS). At the 6- and 12-month assessment points, the VMS patients on all but the lowest dose of TX-001HR had significant improvement over placebo.

Independent of treatment, the largest correlation observed was between changes in moderate to severe VMS frequency and changes in the MENQOL vasomotor symptom domain score at 12 weeks. The quality of life and moderate to severe VMS frequency were highly correlated, he added (rho=0.561, P less than .0001). Improvements in the other MENQOL domains were also highly correlated with reduction in moderate to severe frequency (P less than .0001 for all).

Among patients who reported significant improvement on the MENQOL, more of the TX-001HR patients had improvements that were judged to be clinically significant compared to those taking placebo. Women who experienced a minimal clinically important difference in their symptoms had a weekly improvement of 34 fewer VMS events. Those who had a stronger response which was judged to be clinically important had a weekly improvement of 44 fewer VMS events.