Research gives nod to lower-dose HRT
How many postmenopausal women in your care have begun hormone replacement therapy (HRT), only to discontinue its use due to such initial side effects as irregular bleeding? Recent research now indicates that new lower-dose forms of HRT are just as effective as commonly prescribed doses in relieving vasomotor symptoms and improving vaginal atrophy, while producing higher rates of amenorrhea.1,2
About a third of U.S. women over age 50 take some form of HRT to relieve menopausal symptoms or to reduce risk of osteoporosis.3 Side effects include vaginal bleeding, the top reason for HRT discontinuation.3
Based on the research, Wyeth-Ayerst Labora-tories in Philadelphia has moved to introduce a lower-dose version of Prempro, its combined HRT drug. Prempro contains 0.625 mg of conjugated equine estrogens (CEE) and 2.5 mg of medroxyprogesterone acetate (MPA).
According to Wyeth-Ayerst spokeswoman Audrey Ashby, the company received an approvable letter from the Food and Drug Administration in April 2001. The letter serves as an indication that the agency is prepared to approve the company’s application upon the satisfaction of specified conditions.
"Discussions with the agency are ongoing," states Ashby. "Based on the current status, we are projecting a third-quarter launch of Prempro 0.45 [conjugated estrogens] /1.5 MPA."
More choices in terms of estrogen dose for combination formulations would be a welcome addition to therapy, says Andrew Kaunitz, MD, professor and assistant chair in the obstetrics and gynecology department at the University of Florida Health Science Center in Jacksonville.
Oral and transdermal estrogen replacement therapy formulations are available in a wide array of doses, notes Kaunitz. In contrast, current combination estrogen-progestin HRT formulations are available in only one dose of estrogen.
Examine the results
The two new papers lead off a series of published research from the Women’s Health, Osteoporosis, Progestin, Estrogen study, a two-year, double-blind, placebo-controlled clinical trial supported by Wyeth-Ayerst.
The study looked at 2,673 postmenopausal women who still had their uterus intact. The design of the study included a one-year basic study focused on menopausal symptoms, endometrial histology, and bleeding profiles, and a two-year substudy that examined bone density and turnover, lipoproteins, and carbohydrate metabolism.
Papers on endometrial histology and plasma lipoproteins are scheduled to be published by summer’s end, with research following in the next two to three months on bone density, according to Wulf Utian, MD, PhD, lead author of the vasomotor symptoms paper. (Contraceptive Technology Update will report results of these papers in upcoming issues.) He serves as executive director of the Mayfield Heights, OH-based North American Menopause Society.
In the study, patients received for one year (13 cycles; in milligrams per day) CEE, 0.625; CEE, 0.625 and MPA, 2.5; CEE, 0.45; CEE, 0.45 and MPA, 2.5; CEE, 0.45 and MPA, 1.5; CEE, 0.3; CEE, 0.3 and MPA, 1.5; or placebo.
In the vasomotor symptom/vaginal atrophy paper, researchers compared the frequency and intensity of hot flashes, as well as charted changes in the vaginal maturation index, a measurement of vaginal atrophy. The lower doses appeared to be just as effective as the most commonly prescribed doses, and they should be considered as initial treatment options for a majority of women, researchers conclude.
In the endometrial bleeding paper, researchers analyzed bleeding data from the eight treatment groups. They found that the lower doses of CEE and MPA produced higher rates of amenorrhea than the most commonly prescribed doses, especially during the earlier cycles of therapy. The results suggest that lower doses may be the appropriate choice of therapy in newly menopausal patients, conclude the researchers.
"The major reason for stopping taking HRT in postmenopausal women is the occurrence of bleeding," states the paper’s lead author, David Archer, MD, professor of obstetrics and gynecology and director of the Clinical Research Center at the Eastern Virginia Medical School in Norfolk. "And anything that one can do to reduce this side effect would help with compliance in women staying on the HRT." (See patients’ handouts on HRT in Spanish and English enclosed in this issue.)
References
1. Archer DF, Dorin M, Lewis V, et al. Effects of lower doses of conjugated equine estrogens and medroxyprogesterone acetate on endometrial bleeding. Fertil Steril 2001; 75:1,080-1,087.
2. Utian WH, Shoupe D, Bachmann G, et al. Relief of vasomotor symptoms and vaginal atrophy with lower doses of conjugated equine estrogens and medroxyprogesterone acetate. Fertil Steril 2001; 75:1,065-1,079.
3. Rubin R. Estrogen use best at a lower dose. Studies find fewer side effects in treatment for menopause. USA Today. June 4, 2001; 1A. n
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