Can Premarin (conjugated estrogens) or other vaginal estrogen creams be used on the vulva or external genitalia?

From the Guidelines

Premarin (conjugated estrogens) and other vaginal estrogen creams should not be used on the vulva or external genitalia without consulting a healthcare provider, especially for survivors of estrogen-dependent cancers, due to limited safety data and potential risks. When considering treatment for vulvovaginal atrophy, it's essential to weigh the benefits and risks of vaginal estrogen therapy, as evidenced by a large cohort study of almost 50,000 patients with breast cancer, which showed no increased risk of breast cancer-specific mortality with vaginal estrogen use 1. However, the safety of vaginal hormones has not been firmly established in survivors of estrogen-dependent cancers. For survivors with sexual dysfunction, pelvic floor dysfunction can be treated with pelvic physical therapy, and vaginal dilators may be an option for those with pain during sexual activity or vaginal stenosis from pelvic radiation 1. Topical prescription medications like vaginal estrogen, vaginal androgens (e.g., DHEA), and ospemifene, an FDA-approved selective estrogen receptor modulator, can also be considered for survivors with sexual dysfunction. Key points to consider when using vaginal estrogen creams include:

• Localized application results in minimal systemic absorption compared to oral estrogen therapy
• Potential side effects include local irritation, itching, or discharge
• Women with a history of estrogen-dependent cancers, unexplained vaginal bleeding, or certain cardiovascular conditions should discuss risks with their healthcare provider before using these products
• The panel recommends consideration of ospemifene as an option for dyspareunia in survivors without a history of estrogen-dependent cancers 1.

From the FDA Drug Label

Treatment of moderate to severe symptoms of vulvar and vaginal atrophy associated with the menopause. When prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy, topical vaginal products should be considered.

The provided drug label does mention the treatment of symptoms of vulvar and vaginal atrophy, which implies that estrogen products can be used on the vulva. However, it does not explicitly state that Premarin (conjugated estrogens) or other vaginal estrogen creams can be used on the vulva or external genitalia.

• The label suggests considering topical vaginal products for treating vulvar and vaginal atrophy symptoms, but it does not directly answer the question about using these products on the vulva or external genitalia 2.
• Given the information, a conservative clinical decision would be to consult the specific label for Premarin or the particular vaginal estrogen cream in question, as the provided label is for Estradiol Valerate Injection, USP, which is not a cream.
• Key words: vulvar and vaginal atrophy, topical vaginal products, estrogen products.

From the Research

Use of Premarin or Other Vaginal Estrogen Creams on Vulva/External Genitalia

• Premarin (conjugated estrogens) vaginal cream has been approved by the FDA for the treatment of moderate to severe dyspareunia due to vulvar and vaginal atrophy associated with menopause 3.
• Vaginal estrogen therapy, including Premarin, is generally recommended for the treatment of vulvar and vaginal atrophy (VVA) at the lowest effective dose 4.
• Studies have shown that low-dose synthetic conjugated estrogens A (SCE-A) cream and conjugated estrogens (CE) cream are effective in treating VVA in postmenopausal women, with improvements in vaginal maturation index, pH, and severity of symptoms 5, 6.
• However, there is no consensus on the long-term safety of local estrogen cream, and it is recommended to use hormone therapy for the shortest duration possible 7.
• The use of vaginal conjugated equine estrogen (CEE) cream has not shown any additional positive effect on vaginal health in pessary use for pelvic organ prolapse 7.

Application and Dosage

• Premarin vaginal cream can be used twice weekly for the treatment of moderate to severe VVA 3.
• Low-dose SCE-A cream (1 g = 0.625 mg) administered twice weekly has been shown to be effective in treating VVA in postmenopausal women 5.
• Conjugated estrogens cream (0.3 mg) can be used once daily (21 days on/7 days off) or twice weekly for 12 weeks, followed by open-label treatment for 40 weeks 6.

Safety and Efficacy

• Low-dose CE cream has been shown to be safe and effective in relieving symptoms of VVA, with no report of endometrial hyperplasia or carcinoma 6.
• Adverse events have occurred with similar frequency among active and placebo groups during the double-blind phase of studies 6.