Genitourinary Syndrome of Menopause: An Overview and Hormonal Treatment Insights

Introduction to GSM

Genitourinary syndrome of menopause (GSM) is a progressive and chronic condition caused by the depletion of levels of estrogen and androgens during the menopause transition, and encompasses a range of vulvovaginal, urinary and sexual symptoms. Common presentations include dyspareunia, dryness and irritation of the vagina, urinary urgency, dysuria, and frequent urinary tract infection (UTI). The term GSM is a more encompassing term to describe all the systems that are affected by lack of hormones in women. The term was first adopted in 2014. (1)

Current Management Guidelines

Management of GSM is centered on symptom relief, improvement of tissue health and prevention of recurrence, all while considering patient preferences, comorbidities and safety profiles of available therapies. The 2025 joint guidelines from the American Urological Association (AUA), Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction (SUFU) and the American Urogynecologic Society (AUGS) emphasize an individualized, patient-centered approach grounded in shared decision-making. This process involves discussing the full spectrum of treatment options, potential benefits, risks, costs and ease of use, ensuring alignment with each woman’s lifestyle and health goals. (2)

A recent study looked at how topical vaginal estrogens are a cost-conscious way to improve the burden of UTI on postmenopausal women with the potential for saving billions of dollars in Medicare. The authors concluded that these therapies should be made available as prophylaxes for postmenopausal patients. Over the course of the study, 38% of patients randomized to topical estrogen experienced UTI compared to 75% of placebo patients. Despite recommendations from many organizations for use in postmenopausal patients with recurrent UTI, vaginal estrogen remains underprescribed. Barriers include: provider prescribing habits, lack of education, patient hesitancy, cost, and ease of use.  In addition, the black box warning featured on topical hormonal therapies generates significant concern by the general population. Both topical and oral hormonal therapies feature this warning as a result of the 2002 Women’s Health Initiative (WHI). However, the risks published in the WHI are associated with oral estrogen and progestin supplementation while topical estrogens have demonstrated an excellent safety profile despite the black box warning, exhibiting limited systemic absorption and limiting the risk of breast or endometrial cancer, stroke, pulmonary embolism or deep vein thrombosis. (3)

Hormonal Treatment: Estriol

Estriol exerts a localized action on vaginal tissues with a lower estrogenic potency than estradiol and a greater affinity for estrogen receptor beta (Erb) which minimizes the extravaginal effects. (4)

In Europe, vaginal estriol (E3) is the most frequently chosen estrogen for GSM treatment and has been reported to reduce symptoms of vulvovaginal atrophy, dyspareunia and even risk of lower UTI. (5) While a commercially available product is unavailable in the U.S. , it can be compounded by a pharmacy under the order of a provider with prescriptive authority (i.e.: MD, DO, NP, PA).

Clinical studies support E3’s benefits in restoring vaginal pH, improving mucosal elasticity and alleviating urinary symptoms, which collectively contribute to better sexual comfort and reduced infection risk. (6).

Hormonal Treatment: Testosterone

Testosterone therapy has short-term efficacy in the treatment of sexual function enhancement, particularly hypoactive sexual desire (HSDD) in postmenopausal women. Increases in libido, arousal, orgasm frequency and sexual satisfaction have been found through meta-analyses. Hirsutism and acne are common side effects. (7)

Specifically for GSM, vaginal testosterone has been promising to improve vaginal epithelial health, lower pH, raise maturation indices and ease dyspareunia, but evidence remains limited.  (8)

Comparative Evidence and Limitations

A 2024 meta-analysis of 46 randomized clinical trials found modest short-term benefits with vaginal estrogen, DHEA, ospemifene and moisturizers, but strong evidence for estriol or testosterone in and of themselves was limited, and long-term safety data remain rare. (9)

Further, non-estrogenic alternatives such as testosterone, DHEA, ospemifene, laser therapy and others have proven to be as beneficial as estrogen in the majority of instances with little or no side effects, according to systematic review of non-estrogen treatment. (10)

Conclusion

Genitourinary syndrome of menopause remains a significant, yet underdiagnosed, condition that impacts the physical, sexual and psychological health of millions of postmenopausal women worldwide. The multifactorial nature of GSM, while stemming from estrogen and androgen deficiency, demands a personalized and multi-pronged management approach. While low-dose vaginal estradiol remains the gold standard due to its strong evidence base and established safety in most populations, alternative hormonal therapies like estriol and testosterone offer important options, especially for women who cannot tolerate or prefer not to use standard formulations.

Looking ahead, future GSM management will likely involve combination strategies such as pairing estrogenic and androgenic therapies with non-hormonal options to address the full symptom spectrum and improve patient adherence. Given the chronic nature of GSM, long-term maintenance therapy, ongoing monitoring and shared decision-making are critical to sustaining benefits while minimizing risks. Ultimately, advancing our understanding through robust, well-designed studies will be essential to refining treatment algorithms and expanding safe, effective options for all women affected by GSM.

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