Transdermal progesterone ineffective for menopausal symptoms

Journal of Family Practice, May, 2003 by Deborah Sturpe

Wren BG, Champion SM, Willetts K, Manga RZ, Eden JA. Transdermal progesterone and its effect on vasomotor symptoms, blood lipid levels, bone metabolic markers, moods, and quality of life for postmenopausal women. Menopause 2003; 10:13-18.

* PRACTICE RECOMMENDATIONS

Transdermal progesterone cream, at the dose used in this study, did not improve menopausal symptoms compared with placebo. The study, however, might not have been large enough to detect a difference if one really exists.

In light of recent safety concerns over the use of other types of hormone replacement therapy, treatment of menopausal symptoms with transdermal progesterone should not be used unless better information supporting its benefit becomes available.

* BACKGROUND

Natural progesterone is touted as treatment for the vasomotor, mood, and sexual disturbances associated with menopause. No well-designed clinical trials have assessed this claim. This study evaluates the effectiveness of transdermal progesterone cream in the treatment of menopausal symptoms.

* POPULATION STUDIED

Investigators recruited 80 study participants from the Sydney Menopause Centre at the Royal Hospital for Women in Australia. Postmenopausal women aged 45 to 70 years were eligible if they suffered at least 1 hot flush daily and had not used drugs or herbs for hot flushes within 8 weeks of study enrollment. The average age of study participants was 54 years, and median time since menopause was 3.2 years.

Women were not enrolled if they had a history of major illness, cancer, vaginal bleeding, thrombosis, or uterine fibroids. Eight women dropped out of the study due to bleeding (n=2), return of hot flushes (n=3), inability to attend appointments (n=1), and noncompliance (n=2). Investigators did not indicate whether dropouts were from the progesterone or placebo group. The study subjects may not be reflective of the average postmenopausal population encountered in family medicine, since participants were recruited from a specialized tertiary referral center.

* STUDY DESIGN AND VALIDITY

In this randomized, blinded study, participants used progesterone cream 32 mg or matching placebo daily for 12 weeks. The progesterone cream used in the study was Pro-Feme, a commercially available product manufactured by Lawley Pharmaceuticals. Participants applied 4 cm (equivalent to 32 mg) once daily to the skin, the manufacturer's recommended dose for treating menopausal women.

There are several limitations to this study. The allocation of the patient to the treatment or control group may not have been concealed from the researcher enrolling patients into the study, and women could have been selectively enrolled. The authors did not provide power analysis for the study, and there may not have been enough participants to detect differences between treatment and placebo, if one existed. Not all women completed every portion of the quality-of-life questionnaires at baseline, and the number completing was inconsistent between study group and symptom area. There was a considerable amount of dropped data between baseline and 12 weeks. This loss of data may have led to underestimation of potential benefit of progesterone.

* OUTCOMES MEASURED

Investigators evaluated menopausal symptoms monthly using the Greene Climacteric Scale and, at the end of the study, the Menopause Specific Quality of Life Questionnaire (MENQOL). The Greene Climacteric Scale assesses 5 symptom areas (vasomotor, somatic, anxiety, depression, and sex response), and the MENQOL assesses 4 types of symptoms (vasomotor, physical, psychosocial, and sex-related). Higher scores indicate more severe symptoms on both instruments. The study also measured serum progesterone, lipid levels, and indices of bone metabolism.

* RESULTS

Severity scores for menopausal symptoms appeared similar between groups at baseline, but statistical analysis was not reported. Investigators did not find a significant decrease in menopausal symptoms between progesterone and placebo based on the Greene Climacteric Scale or MENQOL. No differences were found in serum lipid levels or markers of bone metabolism. Serum progesterone significantly increased in the treatment group compared with placebo, but this increase did not induce a biological response in the endometrium.

Deborah Sturpe, PharmD, BCPS, Department of Pharmacy Practice and Science, University of Maryland School of Pharmacy, Baltimore. E-mail: dsturpe@rx.umaryland.edu.