Estetrol effective in alleviating vasomotor symptoms in postmenopausal women

Key takeaways:

• Women receiving estetrol 15 mg had decreased vaginal atrophy assessed by vaginal epithelial cells.
• Estetrol 15 mg also decreased the intensity score for vaginal dryness and dyspareunia.

Use of the hormone estetrol 15 mg once daily had estrogenic effects in the vagina while decreasing atrophy signs and may be a promising treatment option for menopausal symptoms other than vasomotor symptoms, according to researchers.

“We previously published data on the treatment effect of [estetrol] 2.5, 5, 10 or 15 mg on [vasomotor symptoms] and on endometrial and overall safety,” Ulysse Gaspard, MD, PhD, from the department of obstetrics and gynecology at the University of Liège, Belgium, and colleagues wrote. “Here, we report the effects of [estetrol] on the vaginal epithelial cell maturation index and maturation value, [genitourinary syndrome of menopause] and [health-related quality of life] scored by the Menopause Rating Scale, with special attention on the effect of [estetrol] 15 mg, which is an effective dose for the treatment of [vasomotor symptoms] as documented by the phase 2b study and is the dose studied in two ongoing phase 3 trials.”

This multicenter, double-blind, placebo-controlled, randomized, phase 2 study included 257 postmenopausal women aged 40 to 65 years (mean age, 54.2 years). All women were randomly assigned to estetrol (Nextstellis, Mayne Pharma) 2.5 mg (n = 52), 5 mg (n = 47), 10 mg (n = 54) or 15 mg (n = 49) or placebo (n = 55) once daily for 12 weeks.

The study outcomes were the vaginal maturation index and maturation value, genitourinary syndrome of menopause score and the Menopause Rating Scale to assess health-related quality of life.

Researchers observed decreased parabasal and intermediate vaginal epithelial cells among women who received estetrol 2.5 mg (–12.3 and –7.6, respectively), 5 mg (–20.7 and –11.9, respectively), 10 mg (–15.6 and –21.8, respectively) and 15 mg (–23.4 and –13.4, respectively). All groups also experienced an increase in superficial cells (19.9, 32.6, 37.4, and 36.8, respectively). Women who received estetrol 15 mg experienced a least square mean change of –10.81% in parabasal cells, –20.96% change in intermediate cells and an increase of 34.17% for superficial cells.

In addition, estetrol 15 mg was associated with decreased least square mean intensity score for vaginal dryness (–0.4; P = .03) and dyspareunia (–0.47; P = .0006). Researchers also noted that estetrol 15 mg was associated with fewer reports of vaginal dryness by 41% and reports of dyspareunia by 50%.

The overall Menopause Rating Scale score decreased by a least square mean of –3.1 with estetrol 15 mg and across other estetrol doses was associated with a decreased frequency and severity of vasomotor symptoms (P < .001).

“Overall, estetrol 15 mg had a beneficial effect on most of the reported endpoints and therefore is a promising treatment option for all the symptoms noted previously, which are a major source of distress for many postmenopausal women,” the researchers wrote.