The effectiveness of vitamin D as an alternative to FDA-approved treatment and other therapies for managing vulvovaginal atrophy and sexual inactivity in postmenopausal women. A systematic review and meta-analysis.

Eman Youssef, Mostafa Saad Badie, Doaa Ismail, Aliaa Gamal, Hala Mohamed Eldamanhoury

Journal: International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 2025;170(1):64-81

PMID: 39950755

Abstract

BACKGROUND

Vulvovaginal atrophy (VVA) and sexual inactivity (SI) are prevalent among postmenopausal women (PMW). While hormonal therapies show significant improvement, non-hormonal therapies are considered the first-line for breast cancer women. However, vaginal hormonal therapies are unavailable in all countries, particularly developing countries such as the middle east, and there are no studies that have tested these therapies in women either with a history of breast cancer or those taking endocrine therapies for their cancer.

OBJECTIVE

We conducted this meta-analysis to evaluate the effectiveness of vitamin D (VD), whether alone or in combination with other therapies, in managing VVA and SI in PMW.

SEARCH STRATEGY

A systematic literature search was undertaken on four electronic databases (Web of Science, PubMed, Cochrane, and Scopus) from inception until June 2023.

SELECTION CRITERIA

The randomized controlled trials (RCTs) that used the vaginal maturation index (VMI) and vaginal pH to measure VVA and vaginal dryness and the female sexual function index (FSFI) to measure SI were included in the meta-analysis.

MAIN RESULTS

Eight RCTs (608 PMW) were included, and 222 were assigned to the VD arm. For the oral VD subgroup, there was no statistically significant improvement in the mean difference (MD) of VMI (MD -7.62, 95% confidence interval [CI]: -23.84, 8.59). However, VMI's topical VD subgroup was statistically significant (25.16; 95% CI: 18.74, 31.59). For topical form, the total FSFI score (0.24; 95% CI: -1.72, 2.20) and all FSFI domains did not demonstrate statistically significant improvement except arousal (0.56; 95% CI: 0.12, 1.00). Vaginal pH's oral VD subgroup showed statistically significant improvement (-0.27, 95% CI: -0.50, -0.05) compared to the topical VD. Topical VD subgroup (24.45; 95% CI: 7.14, 41.77) showed a statistically significant increase of vaginal superficial cells, in contrast to the oral VD subgroup (3.25; 95% CI: -5.44, 11.96).

CONCLUSION

Topical VD showed significant improvements in VMI and the arousal subscale of FSFI, whereas oral VD had no substantial improvement except in vaginal pH. VD alone is not a sufficient alternative to other available treatments, and further RCTs are needed to evaluate its effectiveness without any combination with other drugs.

© 2025 International Federation of Gynecology and Obstetrics.

Address: Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.; Faculty of Medicine, Al-Azhar University, Cairo, Egypt.; Faculty of Medicine, Zagazig University, Zagazig, Egypt.; Clinical Pharmacy Department, Faculty of Deraya University, Minia, Egypt.; Consultant Gynecology, New Cairo Hospital, Cairo, Egypt.
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