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Clinical Trial
. 2020 May;27(5):526-534.
doi: 10.1097/GME.0000000000001497.

Efficacy and safety of ultra-low dose 0.005% estriol vaginal gel for the treatment of vulvovaginal atrophy in postmenopausal women with early breast cancer treated with nonsteroidal aromatase inhibitors: a phase II, randomized, double-blind, placebo-controlled trial

Angelica Lindén Hirschberg  1 , Pedro Sánchez-Rovira  2 , Jesús Presa-Lorite  3 , Miriam Campos-Delgado  4 , Miguel Gil-Gil  5 , Elisabet Lidbrink  6 , Javier Suárez-Almarza  7 , Concepción Nieto-Magro  7
Affiliations
Clinical Trial

Efficacy and safety of ultra-low dose 0.005% estriol vaginal gel for the treatment of vulvovaginal atrophy in postmenopausal women with early breast cancer treated with nonsteroidal aromatase inhibitors: a phase II, randomized, double-blind, placebo-controlled trial

Angelica Lindén Hirschberg et al. Menopause. 2020 May.

Abstract

Objective: To assess the efficacy and safety of ultra-low dose 0.005% estriol vaginal gel in women with breast cancer receiving nonsteroidal aromatase inhibitors (NSAIs) and experiencing treatment-related vulvovaginal symptoms and signs.

Methods: Women with hormone receptor-positive early breast cancer receiving NSAIs were randomized to either estriol vaginal gel or placebo for 12 weeks. Vaginal maturation, vaginal pH, and total and individual scores of symptoms and signs of vulvovaginal atrophy were assessed at baseline and at weeks 3 and 12; sexual functioning was also evaluated using the Female Sexual Functioning Index (FSFI) questionnaire, as well as circulating estrogens, follicle-stimulating hormone (FSH) and luteinizing hormone (LH).

Results: Sixty-one women with a mean age of 59 years were included: 50 received 0.005% estriol vaginal gel and 11 received placebo. Active treatment significantly improved maturation value and pH, vaginal dryness and global scores of symptoms and signs. Active treatment also increased the total FSFI score and all the FSFI domains, with the exception of pain. Small oscillations were observed in FSH and LH, which remained within the postmenopausal range. Estriol levels increased initially and normalized by week 12, and estradiol and estrone remained mostly undetectable throughout the study.

Conclusions: Ultra-low dose 0.005% estriol vaginal gel showed efficacy in improving the symptoms and signs of vulvovaginal atrophy. These results, together with minimal oscillations in hormonal levels throughout the treatment, support the use of ultra-low dose 0.005% estriol vaginal gel as a treatment option for vulvovaginal atrophy in women with breast cancer receiving NSAIs with an indication for treatment with vaginal estrogens. : Video Summary:http://links.lww.com/MENO/A531.

Plain language summary

Video Summary:http://links.lww.com/MENO/A531.

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Conflict of interest statement

Financial disclosure/conflicts of interest: PS-R has participated in educational activities sponsored by Roche, Kern-Pharma, Pfizer, Novartis, and Astra Zeneca; has received research support from Roche, BMS, and Merck; fees as consultant or advisory board member from Roche, Pfizer, Novartis, and Daiichi; and grants for attending conferences from Roche, Kern-Pharma, and Pfizer. MG-G has received fees as consultant or advisory board member from Pfizer, Novartis, Roche, and Eisai, and grants for attending conferences from Pfizer and Roche. AL-H has received a grant from ITF Research Pharma for attending a conference. M C-D, EL, and JP-L report no conflicts of interest. JS and CN are full time employees of ITF Research Pharma.

Figures

FIG. 1
FIG. 1
Flow diagram of the patients included in the study.
FIG. 2
FIG. 2
Boxplot of the vaginal maturation (A) and vaginal pH (B) values determined at each of the indicated visits in the active treatment and placebo groups (ITT population). ITT, intent-to-treat.
FIG. 3
FIG. 3
Individual scores of each symptom (A) and signs (B) of vulvovaginal atrophy throughout treatment. Columns and error bars represent median and IQR, respectively. Symptoms/signs severity are presented on a 0-3 scale: 0 = lack of symptoms/signs, 1 = mild, 2 = moderate, and 3 = severe. BL, baseline; IQR, interquartile range; w, week. ∗∗P < 0.001, ∗P < 0.05 for differences between baseline and the given visit.
FIG. 4
FIG. 4
Total scores of symptoms (A) and signs (B) of vulvovaginal atrophy throughout treatment. Columns and error bars represent median and IQR, respectively. BL, baseline; IQR, interquartile range; w, week. ∗∗P < 0.001, ∗P < 0.05 for differences between baseline and the given visit.
See this image and copyright information in PMC

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