What is the comparative efficacy of estrogen cream versus Prasterone (Dehydroepiandrosterone, DHEA) suppository for the treatment of vaginal atrophy and dryness?

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Last updated: March 25, 2025 • View editorial policy

From the Guidelines

Estrogen cream is the most effective treatment for vaginal dryness and atrophy, and it should be considered as the first-line treatment option. According to the NCCN guidelines 1, vaginal estrogen is the most effective treatment for vaginal dryness leading to sexual dysfunction and has been shown to be effective in treating itching, discomfort, and painful intercourse in postmenopausal individuals.

Comparison of Treatment Options

The following are key points to consider when comparing estrogen cream and Prasterone (DHEA) suppository:

  • Estrogen cream directly replaces estrogen in vaginal tissues, improving blood flow, thickness, and lubrication 1.
  • Prasterone (Intrarosa), a DHEA suppository, converts to both estrogen and testosterone locally in vaginal tissues, improving tissue integrity while potentially enhancing sexual response 1.
  • Estrogen cream may be more effective for severe atrophy but carries slightly higher systemic absorption concerns 1.
  • Prasterone might be preferable for women with hormone-sensitive cancers or those wanting to avoid estrogen 1.

Safety and Efficacy

It is essential to consider the safety and efficacy of both treatment options.

  • A large cohort study of almost 50,000 patients with breast cancer followed for up to 20 years showed no evidence that there was a higher risk of breast cancer–specific mortality in those using vaginal estrogen 1.
  • However, the safety data for the use of androgen-based therapy, such as Prasterone, in survivors of hormonally mediated cancers are limited, and it should be used with caution in survivors receiving AI therapy 1.

Treatment Recommendations

Based on the most recent and highest quality evidence, estrogen cream is the recommended treatment option for vaginal atrophy and dryness. However, the choice between estrogen cream and Prasterone (DHEA) suppository should consider the individual's medical history, severity of symptoms, and personal preferences 1.

From the Research

Comparative Efficacy of Estrogen Cream and Prasterone (DHEA) Suppository

  • The efficacy of estrogen cream for the treatment of vaginal atrophy and dryness has been established in several studies 2, 3, 4, 5.
  • A study published in 2018 found that very low-dose estradiol vaginal cream (0.003%) applied twice per week was effective in reducing vaginal dryness severity, decreasing vaginal pH, and increasing superficial cell percentage in postmenopausal women with vaginal atrophy 2.
  • Another study published in 2009 found that low-dose synthetic conjugated estrogens A (SCE-A) cream administered twice weekly was effective in treating moderate to severe vulvovaginal atrophy (VVA) in postmenopausal women 4.
  • A review of the evidence on vaginal DHEA for the treatment of menopause-related atrophy found that while there is some evidence to support its use, independent studies are required to confirm its efficacy 6.
  • The North American Menopause Society has published a position statement on the role of local vaginal estrogen therapy for the treatment of vaginal atrophy in postmenopausal women, which recommends the use of low-dose vaginal estrogen products for the treatment of vaginal atrophy 3.

Key Findings

  • Estrogen cream has been shown to be effective in reducing vaginal dryness severity, decreasing vaginal pH, and increasing superficial cell percentage in postmenopausal women with vaginal atrophy 2, 4, 5.
  • Prasterone (DHEA) suppository may be effective in treating vaginal atrophy, but more studies are needed to confirm its efficacy 6.
  • Low-dose vaginal estrogen products are recommended for the treatment of vaginal atrophy in postmenopausal women 3.

Treatment Options

  • Estrogen cream is a well-established treatment option for vaginal atrophy and dryness 2, 3, 4, 5.
  • Prasterone (DHEA) suppository may be considered as an alternative treatment option, but more studies are needed to confirm its efficacy 6.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.