快樂小藥師 Im pharmacist nichts glücklich

VANCOUVER, BC — A randomized, placebo-controlled trial in healthy women in early menopause who had hot flashes suggests that three-month therapy with oral micronized progesterone alone (without estradiol) poses little or no short-term cardiovascular risk [1].

Lead author Dr Jerilynn C Prior (Centre for Menstrual Cycle and Ovulation Research, University of British Columbia, Vancouver) recently coauthored a report based on the same study, in which progesterone therapy had significantly reduced the intensity and frequency of hot flashes and night sweats in the postmenopausal women [2].

In this new analysis of the trial, Prior et al showed short-term cardiovascular safety. The Framingham general cardiovascular risk profile scores, which were low to begin with due to the enrollment criteria, remained low with progesterone therapy.

Taken together, the findings suggest that healthy women in early menopause who have severe hot flashes and night sweats "have another option . . . [and] could safely take progesterone when they probably should not be taking estrogen," Prior told heart wire.

"Many women are apprehensive about taking progesterone for hot flashes because of a belief that it carries the same risks as estrogen—or even greater," she commented in a statement. "We have already shown that the benefits of progesterone alone have been overlooked. This study demonstrates that progesterone's risks have been overblown."

The study was published online January 21, 2014 in PLOS One.

First RCT of Progesterone, Not Progestin, for Hot Flashes

The study drug was progesterone—specifically Prometrium (oral micronized progesterone, Abbott Laboratories), a natural form of the hormone, which has been available in the US since 1998 and in Canada since 1995 and which is approved only to prevent thickening of the endometrium, which could lead to uterine cancer, Prior explained.

Progestin, on the other hand, is a synthetic hormone that comes in different forms with different effects on the cardiovascular system, she continued. Progestogens include both the natural and synthetic forms of this hormone.

The Women's Health Initiativereport in 2002, which led to a dramatic drop in use of hormone-replacement therapy due to concerns about increased risk of heart disease, breast cancer, stroke, and other serious disease, looked at estrogen plus progestin in menopausal women, Prior noted.

Although progestins have been linked with cardiovascular risk, the researchers hypothesized that progesterone would have a positive effect on cardiovascular-risk markers in healthy postmenopausal women.

For the original trial, they recruited 133 women in the Vancouver area who were newly menopausal (last menstrual period one to 11 years ago) and had hot flashes but were nonsmokers and had no diabetes, hypertension, abnormal lipids, or heart disease. The women were randomized to receive 300 mg/day oral progesterone or placebo.

The current trial comprised 112 women with data for cardiovascular risk markers at baseline and after 12 weeks. Data were available for 108 women for lipid levels, but only about a third to a half of the women had values for C-reactive protein, albumin, D-dimer, or glucose.

Thirty-four women underwent venous occlusion plethysmography. On average, these women were in their mid-50s, had had their last menstrual flow about three years ago, and had a normal body-mass index, blood pressure, and heart rate.

With progesterone therapy, there was a nonsignificant trend toward improved endothelial function, as measured by forearm blood flow, probably due to the small sample size, Prior speculated.

There was no significant effect on markers of inflammation (C-reactive protein and albumin) or coagulation (D-dimer), weight, waist circumference, body-mass index, systolic or diastolic blood pressure, plasma glucose, or serum lipids other than HDL cholesterol. There was, however, a 7.7% significant increase in HDL cholesterol, which has an "unclear" implication, the researchers report.

Trial limitations include its small size, short follow-up, and the use of surrogate end points. Nevertheless, no safety issues were identified, and "it's a baby step, saying that progesterone appears to be safe for the short term," Prior said.

Schering Canada initially and subsequently Besins Healthcare provided the oral micronized progesterone and identical placebo; "these companies were otherwise at arm's length from the conduct and interpretation and publication of these trial data." The authors have no support or funding to report.

References

1. Prior JC, Elliott TG, Norman E, et al. Progesterone therapy, endothelial function and cardiovascular risk factors: A 3-month randomized, placebo-controlled trial in healthy early postmenopausal women. PLoS ONE 2014; 9:e84698. Article 
2. Hitchcock CL, Prior JC. Oral micronized progesterone for vasomotor symptoms in healthy postmenopausal women—a placebo-controlled randomized trial. Menopause 2012;19: 886–893. Abstract