Statins, diet changes offer hope for patients at risk for heart attacks, diabetes

Christina Espinoza works out five-to-seven times a week and has gone from a size 13 to a size 8 in the past year. But the weight loss and higher energy level aren't highest on her list of what she's grateful for. For the 30-year old Sacramento marketing coordinator, it is more important that her periods are normal, her chances of having a heart attack or developing diabetes are now lower and, maybe the biggest immediate relief, her facial hair doesn't grow as fast as it used to.

"I used to pluck for 30 minutes every single day," said the mother of two. "Now it's only 15 to 20 minutes," Espinoza said.

Espinoza is one of nearly 7 million women in the United States who suffer from polycystic ovary syndrome (PCOS), a poorly understood disease characterized by an increased production of male hormones - also known as androgens - resulting in infertility, irregular periods, increased hair growth (called hirsutism) and, in about half the cases, obesity. The syndrome raises a woman's risk of developing diabetes three to six times and of having a heart attack four to seven times.

Despite these health risks, scientists do not know what causes PCOS, and physicians have few scientifically proven treatments to offer women like Espinoza. UC Davis researchers Sidika Kasim-Karakas and Antoni Duleba are working to change that.

"We are looking to characterize the hormonal and metabolic profiles of women with PCOS," said Duleba, a professor of reproductive endocrinology and infertility, who recently joined UC Davis from Yale University. "This will guide our research and, hopefully, lead us to better treatments."

Duleba and Kasim-Karakas want to go beyond treating the individual symptoms of PCOS. Current treatments include birth control pills for regulating periods, infertility treatments to achieve pregnancy and medication to reduce hair growth. Instead, the UC Davis physicians are working to discover the cause of PCOS and identify medical and dietary treatments for the syndrome.

Espinoza, for one, swears by walnuts. She was part of a UC Davis clinical trial conducted by Kasim-Karakas in which she was asked to include a specific amount of walnuts in her diet.

New UC Davis infertility specialist Antoni J. Duleba collaborates with UC Davis endocrinologist Sidika Kasim-Karakas to help women with polycystic ovary syndrome.

"I started to have regular periods all on my own," said Espinoza, who had never had a regular menstrual cycle before.

Kasim-Karakas, an endocrinologist and professor of medicine, cautions that the trial in which Espinoza participated is still underway and conclusions have yet to be made with respect to the benefits of walnuts for PCOS patients. The study will eventually include 80 women and should be completed within a year. It compares the benefits of walnuts versus almonds for PCOS patients. According to Kasim-Karakas, books and magazines targeted to women with PCOS often tell them to eat certain foods or dietary supplements.

"The truth is that there is not a single study to support any of those claims," she said.

Kasim-Karakas' research focuses on determining which functional foods, those with proven benefits like fish and nutraceuticals, such as fish oil capsules, actually will help physicians manage PCOS, a chronic disease whose effects on a woman's health changes over time. In a study published earlier this year, she found that restricting simple sugars and carbohydrates and replacing them with protein was beneficial for PCOS patients. In addition to the study involving nuts, she is starting another study comparing the relative benefits of fish oil and flax seed oil for PCOS patients.

Duleba also is conducting a clinical trial aimed at reducing cardiovascular risk factors in women with PCOS using statins, a class of drugs known to reduce cholesterol and  inflammation. Duleba's previous laboratory research showed that androgen production was reduced by using antioxidants, which relieve oxidative stress, or cell damage caused by oxygen free radicals.

"We started looking at mechanisms that regulate ovarian tissue growth and androgen production by ovarian cells," Duleba explained. In testing various antioxidants, Duleba and his colleagues discovered that statins were particularly potent at inducing apoptosis, or programmed cell death, in ovarian tissue. Researchers believe this keeps growth of the tissues to more normal levels and, thus, lowers androgen production.

In a study whereby Duleba and his colleagues treated women with PCOS who were on birth control pills with a statin called simvastatin, the researchers saw a 38 percent decrease in testosterone production and a 45 percent decrease in C-reactive protein (a marker of inflammation) in women who took the drug for 12 weeks versus those on oral contraceptive pills alone. The researchers also saw a reduction in hirsutism.

Encouraged by these results, Duleba and his colleagues are currently investigating whether simvastatin alone can help women with PCOS. They are also continuing laboratory research into the cellular mechanisms behind the syndrome.

Both Duleba and Kasim-Karakas are hopeful that they will be able to offer their patients proven treatments for PCOS in the not-too-distant future. That is welcome news for Espinoza.

"I was very lucky to have been involved in these trials," Espinoza said. "I am very excited that more doctors are focusing their efforts on better understanding of PCOS and on treating women like me."

Duleba's studies are funded by grants from the National Institutes of Health. Kasim-Karakas' current research is supported by the National Center for Complementary and Alternative Medicine (NCCAM), one of the National Institutes of Health.

The UC Davis Health System's Division of Reproductive Endocrinology and Infertility treats a variety reproductive endocrine problems, including amenorrhea, premature ovarian failure, endometriosis, pelvic pain and habitual pregnancy loss. The division's Fertility Center offers a variety of medical and surgical treatments for infertility such as microsurgery, laser surgery, in vitro fertilization and gamete intrafallopian transfer.