Pharmacology Update: Estradiol Acetate Vaginal Ring (Femring—Warner Chilcott)

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD

The FDA has recently approved a vaginal estrogen ring for the treatment of symptoms associated with menopause. The self-inserted ring releases 50 mg or 100 mg of estradiol daily for 3 months. It is manufactured by Galen Ltd of Northern Ireland and will be marketed by Warner Chilcott, Inc as "Femring." This will be the second vaginal estrogen ring available along with Estring.

Indications

Estradiol acetate vaginal ring is indicated for the treatment of moderate to severe vasomotor symptoms as well as moderate-to-severe symptoms of vulvar and vaginal atrophy associated with menopause.1

Dosage

The vaginal ring is inserted into the vagina and left in place for 3 months at which time it should be replaced with a new ring. The starting dose is 50 mg/d.

If the ring is expelled from the vagina, it can be reinserted after rinsing in lukewarm water.1

Femring is available as 50 mg/d and 100 mg/d.

Potential Advantages

The flexible ring can be self-inserted by women every 3 months and releases estradiol acetate in the vagina for a 3-month period. This may be more convenient than daily pills or weekly patches for some women. The absorbed estrogen relieves local symptoms of vaginal and vulvar atrophy, as well as vasomotor symptoms of menopause. In patients with recurrent symptomatic, bacteriological confirmed urinary tract infections, a vaginal ring (Estring) was more effective in reducing recurrent infections. In a 36-week study, 45% of patients remain infection-free compared to 20% for no treatment (P = .008).2

Potential Disadvantages

Estrogen is associated with increased risks of endometrial hyperplasia and cancer. The release from the vaginal ring is unopposed. The Women’s Health Initiative (WHI) study also reported that it could increase the risks of myocardial infarction stroke, invasive breast cancer, pulmonary emboli, and deep-vein thrombosis in postmenopausal women.3

Comments

Femring is a flexible ring that releases estradiol acetate for a 3-month period. In a 13-week double-blind, placebo-controlled trial (n = 325), it was found to relieve both the frequency and symptoms of moderate-to-severe vasomotor symptoms. The 50 mg/d dose decreased the mean weekly number of moderate-to-severe vasomotor symptoms from 73.8 to 21.6 and 75 to 11.4 with the 100 mg dose.1 The severity of symptoms was reduced by 31% and 54%, respectively. Estradiol acetate ring also increased vaginal superficial cells (16-19%) and increased vaginal pH (0.60-0.73). Estring, another vaginal ring, has also been reported to reduce urinary tract infections in patients with recurrent infections. The wholesale cost for Femring is $76.50 for 50 mg and $81.50 for the 100 mg dose. The cost for Estring is $86.88.

Clinical Implications

The WHI study significantly changed the use of estrogen with or without progestins in postmenopausal women. The new boxed warning introduced by the FDA highlights the increased risk for heart disease, heart attacks, strokes, and breast cancer.4 Consideration for use includes treatment of moderate-to-severe vasomotor symptoms and treatment of moderate-to-severe symptoms of vulvar and vaginal atrophy associated with menopause. Vaginal rings such as Estring or Femring are options for treating these indications. The American College of Obstetricians and Gynecologists suggest that vaginal cream, vaginal tablets, or vaginal rings may be considered for genitourinary symptoms. Estrogens in any form should be used at the lowest dose and for the shortest duration possible.

Dr. Elliott is Chair of the Formulary Committee, Northern California Kaiser Permanente and Asst. Clinical Professor of Medicine, University of California-San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA.

References

1. Femring Product Information. Warner Chilcott Inc., March 2003.

2. Eriksen BC. Am J Obstet Gynecol. 1999;180(5): 1072-1079.

3. WHI Investigators. JAMA. 2002;288:321-333.

4. FDA Press Release. January 8, 2003.