Is progestin required with vaginal estrogen ring therapy?

From the Guidelines

No, progestin is not typically required with vaginal estrogen ring therapy. Vaginal estrogen rings deliver a low, localized dose of estrogen that primarily affects vaginal tissues with minimal systemic absorption. This localized action means that endometrial stimulation is minimal, so the addition of progestin to protect the endometrium from hyperplasia is generally unnecessary, as supported by the concept that progesterone added to hormone replacement with estrogen decreases the risk for type 1 endometrial cancer 1. The standard regimen involves inserting the ring into the upper third of the vagina where it remains for 90 days (Estring) or 3 months (Femring) before replacement. This differs from systemic hormone therapy, where combined estrogen-progestin therapy is recommended for women with an intact uterus to prevent endometrial cancer. However, if a patient experiences unexpected vaginal bleeding while using a vaginal estrogen ring, they should contact their healthcare provider for evaluation, as this could indicate endometrial stimulation requiring further assessment. Key points to consider include:

• The localized effect of vaginal estrogen rings minimizes systemic absorption and endometrial stimulation.
• The primary use of vaginal estrogen rings is for the treatment of vaginal atrophy and related symptoms, not for systemic hormone replacement.
• Patients with a history of endometrial cancer or those at high risk for endometrial cancer may require closer monitoring or alternative therapies.
• The decision to add progestin should be based on individual patient risk factors and medical history, rather than as a routine practice for all patients using vaginal estrogen rings.

From the Research

Vaginal Estrogen Ring Therapy and Progestin

• The use of vaginal estrogen ring therapy may require the addition of progestin to protect against endometrial hyperplasia and cancer in women with an intact uterus 2, 3, 4, 5.
• Studies have shown that unopposed estrogen therapy can increase the risk of endometrial hyperplasia and cancer, while the addition of progestin can reduce this risk 2, 4.
• The type and dose of progestin used can affect the risk of endometrial hyperplasia and cancer, with some progestins being more effective than others 5.
• The use of progestin and metformin together may be associated with lower relapse rates and similar remission, clinical pregnancy, and live birth rates compared to progestin therapy alone in women with atypical endometrial hyperplasia or early endometrial cancer 6.

Endometrial Protection

• Progestin is necessary for endometrial protection in women with an intact uterus who are using estrogen therapy 2, 3, 4, 5.
• The addition of progestin to estrogen therapy can reduce the risk of endometrial hyperplasia and cancer, and improve adherence to therapy 2, 4.
• Different progestins may have varying effects on endometrial protection, and the choice of progestin should be based on individual patient needs and medical history 5.

Clinical Implications

• Women with an intact uterus who are using vaginal estrogen ring therapy should be considered for progestin therapy to protect against endometrial hyperplasia and cancer 2, 3, 4, 5.
• The type and dose of progestin used should be individualized based on patient needs and medical history 5.
• Women with atypical endometrial hyperplasia or early endometrial cancer may benefit from progestin and metformin therapy, which may be associated with lower relapse rates and similar remission, clinical pregnancy, and live birth rates compared to progestin therapy alone 6.