44 Women’s Health FAMILY P RACTICE N EWS • June 1, 2005 Simvastatin Trial Suggests Metformin Reduces CV That Statins May Treat PCOS Risk in PCOS Patients BY HEIDI SPLETE tion was associated with sig- BY JANE SALODOF in Poland are conducting the on- control group. Conversely, triglyc- Senior Writer nificant reductions in weight, M ACNEIL going trial in that country. The eride levels increased 21% in the triglycerides, LDL choles- Southwest Bureau women are about 23 years old on OC-only patients but were not WASHINGTON — Met- terol, and blood pressure. average. None received any hor- much changed in OC-simvastatin formin combined with a re- The mean weight loss was L OS A NGELES — Simvastatin monal treatment or OCs for at patients. duced-calorie diet reduced 5 kg (5%), 6 kg (6%), and 5 kg lowered testosterone levels by 41%, least 3 months before enrollment. Increases in HDL cholesterol lev- cardiovascular risk in a study (5%) for women who took normalized gonadotropin levels, Organon Inc. supplied the OC els were similar: 9% with OC-sim- of 791 women with polycys- medication for 12-18 months, and reduced cardiovascular risk fac- Marvelon, and Polfa, a Polish phar- vastatin and 13% with OC alone. tic ovary syndrome, Mofiz 18-24 months, and more than tors in a small, randomized, con- maceutical company, provided Neither group had a significant Haque, M.D., reported in a 24 months, respectively. In trolled trial, suggesting that statins simvastatin. improvement in insulin sensitivity poster presented at the Clin- those three groups, 13%, 14%, may be a potential treatment for A comparison of hormonal lev- or change in body mass index. ical Research 2005 meeting. and 15% of the women lost at polycystic ovary syndrome. els at baseline and 12 weeks Dr. Duleba reported that hyper- The metformin-diet (MET- least 15% of their body “Statins would improve the showed total testosterone fell sig- androgenia declined dramatically D) combination was effective weight. metabolic profile in those patients nificantly—an average of 34.6 in the OC-simvastatin arm, but he in reducing weight, triglyc- Triglyceride levels dropped in terms of lipid levels as well as ng/dL (41%) in the OC-simvas- said 3 months is too early to de- erides, and LDL cholesterol, significantly—by 17 mg/dL— improve the hormonal problems,” tatin group. By contrast, in the termine whether this will lead to while increasing HDL cho- among the 65 women who study investigator Antoni J. Dule- OC-alone group, levels fell by only improvements in excessive hair lesterol, reported Dr. Haque followed the MET-D regimen ba, M.D., said at the annual meet- 10.9 ng/dL (14%). growth or other clinical conditions of the cholesterol center at for 18-24 months. ing of the Society for Gynecolog- Average dehydroepiandros- associated with PCOS. the Jewish Hospital, Cincin- LDL cholesterol levels fell ic Investigation. terone sulfate (DHEA-S) fell 26% The trial employs a crossover nati, and his colleagues. an average of 6 mg/dL (4%) The study is the first to demon- in the OC-simvastatin patients and design by which the groups have At baseline, the women had and 9 mg/dL (7%), respec- strate these benefits in women 28% in the OC-alone group. since switched regimens. The in- a median weight of 95 kg; tively, among the 102 women with polycystic ovary syndrome Luteinizing hormone (LH), how- vestigators also are looking at 15% were overweight, 46% who followed the regimen for (PCOS). Dyslipidemia is common ever, was reduced 43% in the OC- biochemical markers of endothe- were obese, and 29% were se- 12-18 months and the 210 with PCOS, but statins are almost simvastatin group vs. 9% in the lial function and cardiovascular verely obese. At baseline, the women who followed the reg- never used in PCOS, because the OC-alone cohort. risk. mean triglyceride level was imen for more than 24 patients are typically young FSH declined 8%, which was “We used to only see women 108 mg/dL, LDL cholesterol months. women trying to get pregnant or not significant, in the OC-simvas- who wanted to get pregnant and, was 116 mg/dL, and HDL HDL cholesterol levels are at risk of getting pregnant. tatin patients, but it increased 21% on occasion, because of complaints cholesterol was 46 mg/dL. rose an average of 2 mg/dL Statins are contraindicated in preg- in those taking just OCs. of hirsutism,” he said. “Now, with Women with a BMI less (6%) and 4 mg/dL (8%) nancy, said Dr. Duleba of Yale Uni- The LH:FSH ratio declined sig- greater understanding of cardio- than 25 kg/m2 were given a among women who followed versity, New Haven. nificantly in the OC-simvastatin vascular risk factors, people come 2,000-calorie per day diet, and the regimen for 18-24 months The study eliminated pregnancy group (44%) and fell by 12% in the to the office and say, ‘What can we those with a BMI of 25 and more than 24 months, re- as a consideration by placing all 48 OC-alone group—not a statistical- do to protect ourselves from heart kg/m2 or higher were given spectively. Both increases study participants on oral contra- ly significant decline. disease, diabetes, high blood pres- a 1,500-calorie diet. Each diet were statistically significant. ceptive pills (OC) containing 20 As expected, the simvastatin sure—all the cardiovascular prob- included 26% of calories About 75% of women with mcg of ethinyl estradiol and 150 group had a significantly improved lems that our mothers, aunts, and from protein and 44% from polycystic ovary syndrome mcg of desogestrel. One 24-pa- metabolic profile: Total cholesterol grandmothers had?’ ” carbohydrate, they noted at are obese, with unhealthy tient cohort was treated with 20 was 10% lower with OC-simvas- Although he would not recom- the meeting, sponsored by triglyceride and cholesterol mg of simvastatin daily, along with tatin vs. 8% higher with OC alone. mend statins to women trying to the American Federation for levels. MET-D appears to be OC; the other 24 patients received Low-density lipoprotein (LDL) get pregnant, he concluded that Medical Research. an effective strategy for help- only OC. cholesterol dropped a significant statins could eventually prove to be Overall, metformin target- ing them lose weight and re- Investigators from Yale and Poz- 24% in the OC-simvastatin pa- the answer to their question about ed to 2,500 mg/day in com- duce associated cardiovascu- nan University of Medical Sciences tients, but stayed the same in the cardiovascular risk. ■ bination with dietary restric- lar risk factors, they noted. ■ Switching Patients From Valproate May Reverse Hormonal PCOS

BY BRUCE JANCIN longer than 2 years. They ranged in age to the insulin resistance that is one of the which investigators evaluated 50 consecu- Denver Bureau from 16 to 27 years, and nine had been di- first manifestations of PCOS. tive women with epilepsy aged 38-64 years agnosed with juvenile myoclonic epilepsy. There are some data to suggest that whose seizures began prior to age 41. A B RECKENRIDGE, COLO. — Hor- All 16 patients had the elevated testos- there is a dose-dependent relationship be- control group included 82 age-matched monal evidence of polycystic ovary syn- terone and/or FSH levels that help define tween the use of valproate and PCOS. It neurologically normal women. Of the drome in patients on valproate is often re- PCOS. may be possible to use the drug at lower women with epilepsy, 14% had onset of versed by a switch to one of the newer Patients were initially switched from doses without increasing the risk of the menopause prior to 42 years, compared antiepileptic drugs, Jacci Bainbridge, valproate to lamotrigine (Lamictal). If their hormonal/metabolic disorder. That’s wel- with just 4% of controls (Epilepsia Pharm.D., reported at a conference on seizures worsened on the new medica- come news because valproate remains a 2001;42:1584-9). epilepsy syndromes sponsored by the Uni- tion, they were switched again, this time to useful drug in certain circumstances. In another study, Cynthia L. Harden, versity of Texas at San Antonio. levetiracetam (Keppra). Eleven women fin- “Patients with refractory primary gen- M.D., of Columbia University, New York, Women with epilepsy are known to have ished the study on lamotrigine. eralized epilepsy are going to end up on demonstrated that seizure frequency and an increased frequency of polycystic ovary All five patients who were switched to multiple medications—and one of them is lifetime number of seizures were associ- syndrome (PCOS), a common complica- levetiracetam became seizure free. Of the often Depakote [valproate],” noted Dr. ated with earlier age at menopause, ac- tion of valproate therapy. Evidence that the 16 patients, 15 lost hormonal evidence of Cavazos of the University of Texas at San cording to Dr. Cavazos. associated adverse neuroendocrine changes PCOS during the switch from valproate, Antonio. She surveyed 68 women with epilepsy are reversible with a change in seizure med- she said. Seizures can entail hypothalamic storm, whose mean age at menopause was 47.8 ication comes from a recent study by in- Conference director Jose F. Cavazos, with resultant long-term adverse effects on years. The 15 women classified as having a vestigators at the University of Birming- M.D., said that rather than doing routine the hypothalamic-pituitary-ovarian axis. low-seizure-frequency history had a mean ham (England), said Dr. Bainbridge of the hormone measurements in his valproate- One outcome can be premature ovarian age at menopause of 49.9 years, compared University of Colorado, Denver. treated patients in an effort to identify failure, which is more common in women with 47.7 years in the intermediate-seizure- At the annual meeting of the American those with hyperandrogenism, he relies with epilepsy. This helps explain the rela- frequency group and 46.7 years in the 28 Epilepsy Society, the British investigators re- upon sudden weight gain as an early tively low birth rate among women with women with high seizure frequency. The ported on 16 women with generalized clinical tip-off to the presence of PCOS. epilepsy, he said. age difference was statistically significant epilepsy who had been taking valproate for Weight gain in this setting is often due Dr. Cavazos mentioned one study in (Neurology 2003;61:451-5). ■