Simvastatin Trial Suggests That Statins May Treat PCOS

LOS ANGELES — Simvastatin lowered testosterone levels by 41%, normalized gonadotropin levels, and reduced cardiovascular risk factors in a small, randomized, controlled trial, suggesting that statins may be a potential treatment for polycystic ovary syndrome.

“Statins would improve the metabolic profile in those patients in terms of lipid levels as well as improve the hormonal problems,” study investigator Antoni J. Duleba, M.D., said at the annual meeting of the Society for Gynecologic Investigation.

The study is the first to demonstrate these benefits in women with polycystic ovary syndrome (PCOS). Dyslipidemia is common with PCOS, but statins are almost never used in PCOS, because the patients are typically young women trying to get pregnant or are at risk of getting pregnant. Statins are contraindicated in pregnancy, said Dr. Duleba of Yale University, New Haven.

The study eliminated pregnancy as a consideration by placing all 48 study participants on oral contraceptive pills (OC) containing 20 mcg of ethinyl estradiol and 150 mcg of desogestrel. One 24-patient cohort was treated with 20 mg of simvastatin daily, along with OC; the other 24 patients received only OC.

Investigators from Yale and Poznan University of Medical Sciences in Poland are conducting the ongoing trial in that country. The women are about 23 years old on average. None received any hormonal treatment or OCs for at least 3 months before enrollment. Organon Inc. supplied the OC Marvelon, and Polfa, a Polish pharmaceutical company, provided simvastatin.

A comparison of hormonal levels at baseline and 12 weeks showed total testosterone fell significantly—an average of 34.6 ng/dL (41%) in the OC-simvastatin group. By contrast, in the OC-alone group, levels fell by only 10.9 ng/dL (14%).

Average dehydroepiandrosterone sulfate (DHEA-S) fell 26% in the OC-simvastatin patients and 28% in the OC-alone group. Luteinizing hormone (LH), however, was reduced 43% in the OC-simvastatin group vs. 9% in the OC-alone cohort.

FSH declined 8%, which was not significant, in the OC-simvastatin patients, but it increased 21% in those taking just OCs.

The LH:FSH ratio declined significantly in the OC-simvastatin group (44%) and fell by 12% in the OC-alone group—not a statistically significant decline.

As expected, the simvastatin group had a significantly improved metabolic profile: Total cholesterol was 10% lower with OC-simvastatin vs. 8% higher with OC alone. Low-density lipoprotein (LDL) cholesterol dropped a significant 24% in the OC-simvastatin patients, but stayed the same in the control group. Conversely, triglyceride levels increased 21% in the OC-only patients but were not much changed in OC-simvastatin patients.

Increases in HDL cholesterol levels were similar: 9% with OC-simvastatin and 13% with OC alone.

Neither group had a significant improvement in insulin sensitivity or change in body mass index.

Dr. Duleba reported that hyperandrogenia declined dramatically in the OC-simvastatin arm, but he said 3 months is too early to determine whether this will lead to improvements in excessive hair growth or other clinical conditions associated with PCOS.

The trial employs a crossover design by which the groups have since switched regimens. The investigators also are looking at biochemical markers of endothelial function and cardiovascular risk.

“We used to only see women who wanted to get pregnant and, on occasion, because of complaints of hirsutism,” he said. “Now, with greater understanding of cardiovascular risk factors, people come to the office and say, 'What can we do to protect ourselves from heart disease, diabetes, high blood pressure—all the cardiovascular problems that our mothers, aunts, and grandmothers had?'”

Although he would not recommend statins to women trying to get pregnant, he concluded that statins could eventually prove to be the answer to their question about cardiovascular risk.

LOS ANGELES — Simvastatin lowered testosterone levels by 41%, normalized gonadotropin levels, and reduced cardiovascular risk factors in a small, randomized, controlled trial, suggesting that statins may be a potential treatment for polycystic ovary syndrome.

“Statins would improve the metabolic profile in those patients in terms of lipid levels as well as improve the hormonal problems,” study investigator Antoni J. Duleba, M.D., said at the annual meeting of the Society for Gynecologic Investigation.

The study is the first to demonstrate these benefits in women with polycystic ovary syndrome (PCOS). Dyslipidemia is common with PCOS, but statins are almost never used in PCOS, because the patients are typically young women trying to get pregnant or are at risk of getting pregnant. Statins are contraindicated in pregnancy, said Dr. Duleba of Yale University, New Haven.

The study eliminated pregnancy as a consideration by placing all 48 study participants on oral contraceptive pills (OC) containing 20 mcg of ethinyl estradiol and 150 mcg of desogestrel. One 24-patient cohort was treated with 20 mg of simvastatin daily, along with OC; the other 24 patients received only OC.

Investigators from Yale and Poznan University of Medical Sciences in Poland are conducting the ongoing trial in that country. The women are about 23 years old on average. None received any hormonal treatment or OCs for at least 3 months before enrollment. Organon Inc. supplied the OC Marvelon, and Polfa, a Polish pharmaceutical company, provided simvastatin.

A comparison of hormonal levels at baseline and 12 weeks showed total testosterone fell significantly—an average of 34.6 ng/dL (41%) in the OC-simvastatin group. By contrast, in the OC-alone group, levels fell by only 10.9 ng/dL (14%).

Average dehydroepiandrosterone sulfate (DHEA-S) fell 26% in the OC-simvastatin patients and 28% in the OC-alone group. Luteinizing hormone (LH), however, was reduced 43% in the OC-simvastatin group vs. 9% in the OC-alone cohort.

FSH declined 8%, which was not significant, in the OC-simvastatin patients, but it increased 21% in those taking just OCs.

The LH:FSH ratio declined significantly in the OC-simvastatin group (44%) and fell by 12% in the OC-alone group—not a statistically significant decline.

As expected, the simvastatin group had a significantly improved metabolic profile: Total cholesterol was 10% lower with OC-simvastatin vs. 8% higher with OC alone. Low-density lipoprotein (LDL) cholesterol dropped a significant 24% in the OC-simvastatin patients, but stayed the same in the control group. Conversely, triglyceride levels increased 21% in the OC-only patients but were not much changed in OC-simvastatin patients.

Increases in HDL cholesterol levels were similar: 9% with OC-simvastatin and 13% with OC alone.

Neither group had a significant improvement in insulin sensitivity or change in body mass index.

Dr. Duleba reported that hyperandrogenia declined dramatically in the OC-simvastatin arm, but he said 3 months is too early to determine whether this will lead to improvements in excessive hair growth or other clinical conditions associated with PCOS.

The trial employs a crossover design by which the groups have since switched regimens. The investigators also are looking at biochemical markers of endothelial function and cardiovascular risk.

“We used to only see women who wanted to get pregnant and, on occasion, because of complaints of hirsutism,” he said. “Now, with greater understanding of cardiovascular risk factors, people come to the office and say, 'What can we do to protect ourselves from heart disease, diabetes, high blood pressure—all the cardiovascular problems that our mothers, aunts, and grandmothers had?'”

Although he would not recommend statins to women trying to get pregnant, he concluded that statins could eventually prove to be the answer to their question about cardiovascular risk.

LOS ANGELES — Simvastatin lowered testosterone levels by 41%, normalized gonadotropin levels, and reduced cardiovascular risk factors in a small, randomized, controlled trial, suggesting that statins may be a potential treatment for polycystic ovary syndrome.

“Statins would improve the metabolic profile in those patients in terms of lipid levels as well as improve the hormonal problems,” study investigator Antoni J. Duleba, M.D., said at the annual meeting of the Society for Gynecologic Investigation.

The study is the first to demonstrate these benefits in women with polycystic ovary syndrome (PCOS). Dyslipidemia is common with PCOS, but statins are almost never used in PCOS, because the patients are typically young women trying to get pregnant or are at risk of getting pregnant. Statins are contraindicated in pregnancy, said Dr. Duleba of Yale University, New Haven.

The study eliminated pregnancy as a consideration by placing all 48 study participants on oral contraceptive pills (OC) containing 20 mcg of ethinyl estradiol and 150 mcg of desogestrel. One 24-patient cohort was treated with 20 mg of simvastatin daily, along with OC; the other 24 patients received only OC.

Investigators from Yale and Poznan University of Medical Sciences in Poland are conducting the ongoing trial in that country. The women are about 23 years old on average. None received any hormonal treatment or OCs for at least 3 months before enrollment. Organon Inc. supplied the OC Marvelon, and Polfa, a Polish pharmaceutical company, provided simvastatin.

A comparison of hormonal levels at baseline and 12 weeks showed total testosterone fell significantly—an average of 34.6 ng/dL (41%) in the OC-simvastatin group. By contrast, in the OC-alone group, levels fell by only 10.9 ng/dL (14%).

Average dehydroepiandrosterone sulfate (DHEA-S) fell 26% in the OC-simvastatin patients and 28% in the OC-alone group. Luteinizing hormone (LH), however, was reduced 43% in the OC-simvastatin group vs. 9% in the OC-alone cohort.

FSH declined 8%, which was not significant, in the OC-simvastatin patients, but it increased 21% in those taking just OCs.

The LH:FSH ratio declined significantly in the OC-simvastatin group (44%) and fell by 12% in the OC-alone group—not a statistically significant decline.

As expected, the simvastatin group had a significantly improved metabolic profile: Total cholesterol was 10% lower with OC-simvastatin vs. 8% higher with OC alone. Low-density lipoprotein (LDL) cholesterol dropped a significant 24% in the OC-simvastatin patients, but stayed the same in the control group. Conversely, triglyceride levels increased 21% in the OC-only patients but were not much changed in OC-simvastatin patients.

Increases in HDL cholesterol levels were similar: 9% with OC-simvastatin and 13% with OC alone.

Neither group had a significant improvement in insulin sensitivity or change in body mass index.

Dr. Duleba reported that hyperandrogenia declined dramatically in the OC-simvastatin arm, but he said 3 months is too early to determine whether this will lead to improvements in excessive hair growth or other clinical conditions associated with PCOS.

The trial employs a crossover design by which the groups have since switched regimens. The investigators also are looking at biochemical markers of endothelial function and cardiovascular risk.

“We used to only see women who wanted to get pregnant and, on occasion, because of complaints of hirsutism,” he said. “Now, with greater understanding of cardiovascular risk factors, people come to the office and say, 'What can we do to protect ourselves from heart disease, diabetes, high blood pressure—all the cardiovascular problems that our mothers, aunts, and grandmothers had?'”

Although he would not recommend statins to women trying to get pregnant, he concluded that statins could eventually prove to be the answer to their question about cardiovascular risk.