The need for (vaginal) cream in Perimenopause

In Part 1 of this series, we covered what Genitourinary Syndrome of Menopause (GSM) is, how common it is, and why it tends to get worse over time rather than resolve on its own. This time, we're looking at what the evidence actually shows about treatment, starting with the most well-studied option: vaginal estrogen.

vaginal estrogen

Vaginal estrogen is a low-dose estrogen applied directly to the vaginal tissue, as a cream, tablet, insert, or ring, rather than taken as a pill or worn as a patch. Because it's applied locally, it reaches the vulva, vagina, urethra, and bladder tissue directly, at a much higher local concentration than oral or transdermal estrogen achieves in that tissue.

This matters, because it's a different treatment from systemic hormone replacement therapy (HRT), even though both involve estrogen. Systemic HRT (the pill or patch) is absorbed into the bloodstream and circulates throughout the body, treating a variety of symptoms.

Vaginal estrogen has minimal systemic absorption, it stays largely local to the tissue it's applied to (NAMS, 2022 Hormone Therapy Position Statement).

Why HRT alone often isn't enough

A common assumption is that once someone starts HRT, all their menopause symptoms, including GSM, should improve. Often, that isn't the case.

Oral and transdermal estrogen are effective for vasomotor symptoms and other body-wide effects of estrogen decline. But because they don't concentrate in vaginal, vulvar, and urinary tissue the way local vaginal estrogen does, many women on systemic HRT still experience dryness, pain, or recurrent UTIs, and need vaginal estrogen added specifically to treat those symptoms (Rahn et al., Obstet Gynecol, 2014).

If you're on HRT and still dealing with GSM symptoms, that isn't a sign that HRT has failed. It's a sign that GSM usually needs its own, targeted treatment, on top of whatever is treating your other symptoms.

What the evidence shows about effectiveness

A systematic review of randomized controlled trials found vaginal estrogen effectively treats the vulvovaginal and urinary symptoms of GSM, including dryness, irritation, dyspareunia, and recurrent UTIs, with a favorable safety profile (Rahn et al., Obstet Gynecol, 2014). A Cochrane review of 34 trials involving over 19,000 women reached a similar conclusion, local estrogen improved symptoms compared to placebo (Lethaby et al., Cochrane Database Syst Rev, 2016).

For recurrent UTIs specifically, the evidence is substantial. One large real-world study of 5,638 women found vaginal estrogen reduced UTI frequency by roughly 52% (Tan-Kim et al., Am J Obstet Gynecol, 2023). An even larger analysis, drawing on over 2 million patient records from the Epic Cosmos database, found that in women over 55 with recurrent UTIs, those using vaginal estrogen had significantly lower rates of sepsis (10.6% vs 19.4%) and death (0.42% vs 1.54%) compared to those who weren't using it (Wells et al., J Urology, 2025).

Addressing the safety question

Many women hesitate to use vaginal estrogen because of fears associated with systemic hormone therapy, particularly around breast cancer risk. This is worth addressing directly, because the two treatments have different risk profiles.

Because vaginal estrogen has minimal systemic absorption, it does not carry the same risk profile as oral or transdermal HRT (NAMS, 2022). For breast cancer survivors specifically, observational data suggests low-dose vaginal estrogen appears safe for those who've tried non-hormonal options first, though this is generally recommended in consultation with an oncologist, particularly for women on aromatase inhibitors (NAMS, 2022).

Vaginal DHEA: another option worth knowing about

Vaginal estrogen isn't the only local hormonal treatment with strong evidence behind it. Vaginal DHEA (prasterone), sold under the brand name Intrarosa, is FDA-approved for treating moderate to severe dyspareunia related to GSM.

DHEA works differently from estrogen. It's an inactive precursor that gets converted locally, within the vaginal tissue itself, into small amounts of estrogen and androgen, a process called intracrinology. That local conversion means minimal systemic absorption, similar to vaginal estrogen.

The pivotal phase III trial, involving 482 postmenopausal women (325 on DHEA, 157 on placebo), found daily intravaginal DHEA produced statistically significant improvements in dyspareunia severity, vaginal pH, and vaginal cell changes compared to placebo (Labrie et al., 2016). Because it also delivers a small androgen effect locally, it's sometimes considered an alternative for women who don't respond fully to estrogen alone, or who prefer a different hormonal option.

One thing worth knowing: unlike some vaginal estrogen research, DHEA hasn't been as extensively studied in women with a history of breast cancer, so this is a conversation to have directly with your doctor or oncologist if that applies to you.

What comes next

Vaginal estrogen is the most well-evidenced treatment for GSM, but it isn't the only piece of the picture. In Part 3 of this series, we'll look at the role of pelvic floor physical therapy, something that's often left out of GSM conversations entirely, despite meaningful evidence supporting it, along with non-hormonal options for those who can't or don't want to use estrogen.

This article is for educational purposes only and does not constitute medical advice. Always consult your doctor about your specific symptoms and treatment options.

References:

• The NAMS 2022 Hormone Therapy Position Statement Editorial Panel. The 2022 hormone therapy position statement of The North American Menopause Society. Menopause. 2022;29(7):767-794.

• Rahn DD, Carberry C, Sanses TV, et al. Vaginal estrogen for genitourinary syndrome of menopause: a systematic review. Obstet Gynecol. 2014;124(6):1147-1156.

• Lethaby A, Ayeleke RO, Roberts H. Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database Syst Rev. 2016.

• Tan-Kim J, Shah NM, Do D, et al. Efficacy of vaginal estrogen for recurrent urinary tract infection prevention in hypoestrogenic women. Am J Obstet Gynecol. 2023.

• Labrie F, Archer DF, Koltun W, et al. Efficacy of intravaginal dehydroepiandrosterone (DHEA) on moderate to severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy, and of the genitourinary syndrome of menopause. Menopause. 2016.

• Wells BA, De EJB, Feustel PJ, et al. Impact of Vaginal Estrogen on Serious Adverse Outcomes in Postmenopausal Women with Recurrent Urinary Tract Infections: A Retrospective Study. Abstract IP15-36. The Journal of Urology. 2025.

• Baquedano Mainar L, Nieto-Pascual L, Iglesias Bravo E, et al. Safety of vaginal estrogen in breast cancer survivors: Current evidence on systemic absorption and oncologic outcomes. Maturitas. 2026 May;208:108914. Epub 2026 Mar 12.

• FDA prescribing information: PREMARIN (conjugated estrogens) Vaginal Cream (Initial U.S. Approval: 1942) and INTRAROSA (prasterone) Vaginal Inserts (Initial U.S. Approval: 2016).