A double-blind placebo-controlled study to evaluate the effect of progestelle progesterone cream on postmenopausal women.

OBJECTIVE: To evaluate the effect on climacteric symptoms and quality of life, and the safety of four doses of progestelle progesterone cream administered for 24 weeks to postmenopausal women complaining of moderate to severe menopausal symptoms. Design Single-centre, double-blind, randomized, placebo-controlled study. Population Two hundred and twenty-three healthy postmenopausal women, aged between 40 and 60 years and complaining of severe menopausal symptoms were recruited through newspaper advertisements. METHODS: Women were randomly allocated to progestelle progesterone cream 60, 40, 20, 5 mg or placebo, to be applied daily for six months. Main outcome measures The primary efficacy variable was the psychological, somatic and vasomotor components of the Greene Climacteric Scale after six months. Secondary endpoints were incidence of hot flushes and night sweats, the nine subscales of the Medical Outcome Survey Short Form-36 (SF-36), serum progesterone, endometrial thickness and histology after six months. Adverse events were sought and recorded and followed up to resolution. RESULTS: There were no statistically significant differences between any of the treatment groups and placebo for any of the components of the Greene Score. A statistically significant difference between the 20 mg group and placebo was found for the physical functioning (95% confidence interval [CI] 1.7-12.3; P=0.01) and social functioning (95% CI 1.9-16.7; P=0.01) scales of SF-36 after six months. No other statistically significant differences were found between any treatment group and placebo for any of the other secondary efficacy variables. There appeared to be a higher incidence of headache in the groups treated with progesterone cream. CONCLUSIONS: Progesterone cream was no more effective than placebo for relief of menopausal symptoms.

Double-blind placebo-controlled study to evaluate the effect of pro-juven progesterone cream on atherosclerosis and bone density.

OBJECTIVE: To establish whether treatment for three years with pro-juven progesterone cream affects progression of atherosclerotic plaques or bone density in postmenopausal women. Design Randomized double-blind placebo-controlled trial. Sample One hundred and thirty-one healthy postmenopausal women aged between 50 and 75 years with at least one asymptomatic arterial plaque visible on ultrasound of the carotid or femoral bifurcation. METHODS: Women were randomly allocated to receive pro-juven progesterone cream, 20 mg twice daily, or placebo, for three years. Main outcome measure Rate of change of plaque thickness, intima-media thickness and bone density of lumbar spine and femoral neck. RESULTS: There was no difference between the groups. CONCLUSION: Pro-juven progesterone cream 20 mg twice daily did not affect progression of asymptomatic atherosclerosis or deterioration in bone density over three years.

A study to look at hormonal absorption of progesterone cream used in conjunction with transdermal estrogen.

Natural progesterone creams are gaining popularity as a possible treatment for menopausal symptoms, and many women may be using them with estrogen. We planned to evaluate, using an open plan study, the systemic absorption of a combination of transdermal estrogen and progesterone. Women applied transdermal progesterone 40 mg and transdermal estrogen 1 mg daily over 48 weeks. Women were assessed at intervals of 12 weeks. Significant increases in plasma levels of progesterone and estradiol were seen after 12 weeks, although only low plasma progesterone levels were found (median 2.5 nmol/l) and no further increase was noted over the remainder of the study period. A significant correlation was found between plasma levels of the two hormone (r = 0.315, p = 0.045). Women reported significant reductions in menopausal symptoms, as measured by the Green Climacteric Scale, after 24 and 48 weeks of combined treatment. There may be similar mechanisms of absorption of the two hormones, although the doses used in our study produced sub-luteal levels of progesterone. There was no evidence of accumulation of progesterone with time, and further study is needed to assess the efficacy and safety of this combination of hormones.

Bleeding profiles and effects on the endometrium for women using a novel combination of transdermal oestradiol and natural progesterone cream as part of a continuous combined hormone replacement regime.

OBJECTIVE: Many women are seeking alternatives to conventional forms of hormone replacement. This study evaluates the endometrial effects of natural progesterone cream used in conjunction with transdermal oestradiol. DESIGN: Open plan study conducted over 48 weeks. SETTING: Tertiary referral London teaching hospital. POPULATION: Women at least two years postmenopausal. METHODS: Women were recruited nationally. They applied 40 mg transdermal natural progesterone cream and 1 mg transdermal oestradiol daily. MAIN OUTCOME MEASURES: Endometrial histology, assessed by pipelle endometrial biopsy, ultrasound assessment of endometrial thickness and bleeding diaries. RESULTS: Fifty-four women were recruited of which 41 completed the study. Mean age was 57.4 years. Thirty-two percent of women had evidence of inadequate endometrial opposition (proliferative or hyperplastic) at the end of 48 weeks. At baseline, women had a mean endometrial thickness of 3.3 mm, which had significantly thickened to a mean of 5.3 mm by 24 weeks (P < 0.001). By 48 weeks, there was significantly greater increase in endometrial thickness from baseline in those women who displayed inadequate endometrial opposition, compared with those women who had adequate endometrial opposition (P= 0.004). At 24 weeks, 48% of women had remained entirely amenorrhoeic. By the end of the study, 35% of women had been entirely amenorrhoeic and 50% had had either no bleeding or spotting alone. The number of bleeding episodes did not reduce with time. CONCLUSIONS: The dose of natural progesterone cream in this study was insufficient to fully attenuate the mitogenic effect of oestrogen on the endometrium. We would not recommend this combination of hormones to be used by postmenopausal women.