PCOS and Cardiovascular Risks

Women with Polycystic Ovarian Syndrome (PCOS) have an increased risk for heart disease and possibly heart attacks compared to other women of the same age and weight, studies show. Specifically, the indications of cardiovascular disease include sub-clinical hardening of the arteries and signs of significant vascular impairment, including irregularities of the cells lining the arteries and blood vessels and increased thickness and decreased compliance of arterial walls. While the main focus of PCOS specialists is treating infertility, menstrual irregularities and unwanted hair, it’s important for women and their physicians to pay attention to the increased cardiovascular risk that accompanies PCOS as well, said Dr. Pinar Kodaman, a reproductive endocrine specialist who focuses on reducing cardiovascular risks for PCOS patients through lifestyle modification and medication. Dr. Kodaman is part of the multidisciplinary team at the Yale Polycystic Ovarian Syndrome Program that treats all aspects of PCOS.

Cardiovascular disease remains the most common cause of death among women, and risk of death from a heart attack increases with age, especially in the United States where there is a high incidence of obesity, a key contributor to heart disease.

At least 50% of women with PCOS in the U.S. are obese, 40% are insulin resistant, and 10% have type II diabetes. Insulin resistance, coupled with the body’s tendency to compensate by producing even more insulin, is one of the major factors in the development of Metabolic Syndrome, and this condition exacerbates elevated lipids in the blood, obesity, glucose intolerance and unwanted facial and body hair among women with PCOS.

PCOS is also associated with increased oxidative stress, high blood pressure, elevated levels of homocysteine, an amino acid in the blood that is an indicator of higher risk of heart disease, and dyslipidemia (an imbalance of lipids in the blood), all of which also contribute to cardiovascular risk. Interestingly, even young and lean women with PCOS tend to have unfavorable cardiovascular risk profiles, Dr. Kodaman said.

The studies on cardiovascular illness and death among PCOS patients are limited; however, the cardiovascular risks associated with the syndrome are clear.

The medical management of PCOS includes therapy for failure to ovulate or irregular ovulation, unwanted body and facial hair, as well as treatment of endometrial hyperplasia, a condition in which the lining of the uterus grows too much. In addition, obesity, dyslipidemia, hypertension, and insulin resistance should also be addressed if present. Lifestyle modification with diet and exercise are first line treatments, followed by insulin sensitizers, such as metformin, for insulin resistance and statin drugs, like Lipitor, for dyslipidemia. Statins may have additional beneficial roles in decreasing oxidative stress and improving hyperandrogenemia and other biochemical disorders of PCOS.

PCOS is the most common endocrine disease affecting women of reproductive age. Up to 10 million women in the United States have PCOS, a condition characterized by hyperandrogenism (excessive secretion of male sex hormones that results in unwanted facial and body hair) and oligomenorrhea (irregular menstrual periods). Frequently, the ovaries also have a polycystic appearance on ultrasound, which appears as multiple small follicles around the perimeter of the ovary. The cause of PCOS is unknown and researchers are actively investigating it.

PCOS occurs shortly after puberty and consists of altered gonadotropin secretion favoring luteinizing hormone production, which stimulates the ovaries to produce increased levels of androgens (male sex hormones). In addition, at the level of the ovary, the follicles make less estrogen and luteinize prematurely, thereby failing to ovulate.

While PCOS is an endocrine disorder affecting women during their reproductive years, its consequences continue to have detrimental effects in the postmenopausal years. A recent a study found that postmenopausal women with clinical features of PCOS had a greater incidence of cardiovascular events. Therefore, it is imperative that PCOS be diagnosed in a timely fashion and treated effectively across the lifespan.

PCOS and Nutrition

While the causes of PCOS remain unclear, most experts believe insulin plays a major role in its development. The majority of PCOS patients have decreased insulin insensitivity, causing high levels of insulin or what is commonly known as insulin resistance. Approximately 50% of women affected by PCOS are overweight.

Risk Factors
Insulin resistance places an individual at increased risk for:
• Abnormal carbohydrate metabolism – raising the likelihood of developing type II diabetes
• Heart disease due to:
– Increased levels of LDL or “bad” cholesterol
– Decreased levels of HDL or “good” cholesterol
– Increased levels of triglycerides
– Increased blood pressure
• Significant weight gain and difficulty losing weight
• Low self-esteem

Lifestyle Modifications

Diet
Diet and exercise have been established as the first line of defense against PCOS. Studies show that a 5%-10% weight loss may substantially improve the metabolic and reproductive abnormalities associated with PCOS while lowering the risk of heart disease and type II diabetes. A registered dietitian (RD) can help customize a balanced diet, low in fat and moderate in carbohydrates, to help you achieve and maintain your weight loss goals. The RD will evaluate your current diet, lifestyle and risk factors and
establish a nutrition plan specific to your individual needs.
The following factors will be considered:
• Current height and weight
• Ideal body weight (IBW)
• Age, overall health and medical history
• Current medications or supplements taken
• Current eating patterns, food preferences and dietary customs

Exercise
Evidence clearly supports the importance of physical activity for women affected by PCOS; exercise may be just as important as diet in treating the disorder. Both aerobic exercise and strength conditioning can be effective in:
• Improving lipid levels
• Improving insulin insensitivity
• Lowering blood pressure
• Improving self-esteem
• Managing weight
• Aiding in prevention and treatment of chronic disease

An RD can help develop a customized exercise plan based on your preferences and lifestyle pattern.

Pregnant with PCOS

Pregnant women with PCOS face a number of challenges before, during and after their pregnancies. To address these concerns, Yale’s infertility specialists and Maternal-Fetal Medicine specialists at the Yale PCOS Program provide on-site consultations prior to conception and throughout pregnancy for women likely at high risk for pregnancy-related complications.

Pregnancy Risks
• Infertility – Due to ovulation disturbances, women with PCOS may find it difficult to get pregnant. YFC boasts one of the highest success rates in the region for managing PCOS-related infertility, offering individualized management strategies to minimize the risks of ovarian hyperstimulation and multiple pregnancy while maximizing success of fertility treatments. Fertility therapies include ovulation induction strategies, injectable hormones, aromatase inhibitors and in vitro fertilization.

We also recommend lifestyle interventions that may help with spontaneous ovulation.
• Miscarriage – Women with PCOS may be at increased risk for spontaneous miscarriage. Contributing factors include elevated insulin levels (insulin resistance) and high levels of luteinizing hormone (LH) or androgens (male hormones). Miscarriage risk can be reduced by lowering insulin levels through weight loss or with insulin-lowering medicines such as Metformin. Women with elevated homocysteine levels may also require increased folic acid.
• Pregnancy Complications – Women with PCOS are particularly at risk for gestational diabetes, which may increase the risk of birth defects, miscarriage, preeclampsia, preterm delivery, macrosomia (excessive birth weight) and birth injury. Weight reduction and lowering insulin levels before pregnancy are beneficial to ensuring a healthy pregnancy.
• Multiple Pregnancy – Pregnancy with more than one fetus increases the overall risk for pregnancy-related complications in women with PCOS. Because they are at high risk for multiple pregnancy following fertility treatment compared to women with other causes for infertility, our goal is to minimize this risk by utilizing gentler treatment protocols that reduce the likelihood of multiple gestation.
In addition to working with high-risk pregnant women with PCOS, YFC monitors all PCOS pregnancy outcomes to help the medical community understand the fetal and perinatal implications of PCOS.

Risks to Children of Women with PCOS
Studies suggest that PCOS diagnosis may have implications for the children of women with PCOS.
• Daughters of women with PCOS may grow up to exhibit the characteristic features of PCOS.
• Weight problems, insulin resistance and high cholesterol are consistently seen in children of women with PCOS.

Healthy lifestyle and healthy weight goals are therefore important not just for women with PCOS, but also for their children.

Infertility and PCOS

Ovulation disturbance is the most likely cause of infertility in women with PCOS who do not ovulate regularly, although other factors may contribute to fertility problems in some couples. The Yale PCOS Program provides state-of-the-art management of PCOS-related infertility. With one of the highest success rates in the region, our experts offer individualized management strategies to maximize success while minimizing the risks of ovarian hyperstimulation and multiple pregnancy in patients with PCOS.

Treatment begins with a basic infertility workup:
• Pelvic ultrasound
• Prenatal lab tests
• HSG (hysterosalpingogram) – X-ray of the uterus and fallopian tubes
• SHG (sonohysterogram) – saline ultrasound to determine uterine abnormalities
• Semen analysis
• Complete health assessment, including a risk profile for diabetes, heart disease and other diseases associated with PCOS
After reviewing these test results, we meet with
you to determine the best course of action.

Options include:
• Ovulation induction – A number of medications are available to induce ovulation in women with PCOS; dose and treatment duration are individualized:
– Clomid – orally administered fertility medication
– Gonadotropins – injectable fertility medications for those who do not respond to simpler treatments; more expensive with greater chance of multiple pregnancy
– Aromatase inhibitors – trigger ovulation in women; safer and less expensive than some alternatives
• Insulin sensitizing agents – Metformin has been shown to restore normal ovulation in some women with PCOS, may improve response to other fertility drugs, and has little or no risk of multiple pregnancies.
• In vitro fertilization (IVF) – removing eggs from your body, fertilizing them with your partner’s sperm, and implanting a fertilized egg into your womb. We utilize minimal stimulation and blastocyst culture and transfer strategies to reduce risks for such problems as ovarian hyperstimulation syndrome and multiple pregnancy.
• Lifestyle modifications – Because being overweight or obese may reduce a woman’s fertility, weight loss is highly recommended to improve fertility and pregnancy outcome. We provide a comprehensive lifestyle management program that includes weight management counseling.
• Optimizing Vitamin D status – Our ongoing research indicates lower pregnancy rates following IVF in women with low blood levels of Vitamin D. Vitamin D levels are assessed for all women attending the Yale PCOS Program and treatment provided to achieve normal levels.

Health Risks of PCOS

Women with PCOS are at increased risk fordeveloping a number of long-term health problems. At the Yale PCOS Program, we seek to address these risks before they become serious medical issues, with a combination of lifestyle modifications and medical interventions.
• Endometrial Hyperplasia – A thickening of the endometrium (uterine lining) can cause heavy or irregular bleeding, and may lead to pre-cancerous changes in the endometrium that could develop into endometrial cancer.
• Cardiovascular Disease Risk – Women with PCOS have a greater chance of developing Metabolic Syndrome – a cluster of risk factors that raise the likelihood of a heart attack or stroke later in life.
These factors include:
• Obesity – approximately 50% of women with PCOS in the US are obese
• Dyslipidemia – increased total cholesterol, triglycerides or both and decreased HDL (good cholesterol)
• Elevated blood pressure (hypertension)
• Insulin resistance – 40% of women with PCOS are insulin resistant
• Type II diabetes – affects 10% of women with PCOS
• Sleep apnea – can present as disturbed sleep, frequent sleep interruptions, restlessness, snoring, and daytime fatigue and sleepiness

Given these risk factors, women with PCOS have a seven-fold increased risk for heart attack and are four times more likely to have a stroke compared to women without PCOS.
• Breast Cancer – Some studies indicate that there is a correlation between PCOS and breast cancer, but the evidence so far is inconclusive.

Women with PCOS are encouraged to visit the Yale PCOS Program for a complete metabolic assessment and risk profile. Your initial examination will include a complete medical history, physical exam with BMI measurement, pelvic ultrasound and all appropriate lab tests. Once we have assessed your risk, we will tailor an individualized plan to meet your specific needs.

Cosmetic Concerns and Symptoms of PCOS

Cosmetic concerns are common in women with PCOS. While not hazardous to health, they may be a source of significant psychological distress. The Yale PCOS Program helps women manage bothersome cosmetic concerns with medical interventions, lifestyle modifications, and psychological support and counseling.

Hirsutism
Hirsutism is the excess growth of coarse, visible body hair, which can be evident on the upper lip, around the jaw, on the cheeks, and sometimes on the chest, stomach and upper thighs. Increased male hormone levels and insulin contribute to hirsutism in women with PCOS. Treatments include:
• Anti-androgens* (Flutamide, Finasteride and Spironolactone) – to decrease the male hormone’s effect on hair growth
• Vaniqa (Eflornithine) cream – to reduce facial hair
• Birth control pills* – to decrease production of male hormones
• Non-pharmacological options – such as shaving, bleaching, waxing, electrolysis and laser hair removal

Acne
Acne is common in women with PCOS and is caused by elevated male hormone and insulin levels. Treatments include:
• Anti-androgens* – to counter the effects of the male hormone on skin
• Benzoyl peroxide – a common over-the-counter ingredient used in creams and lotions to treat mild to moderate acne
• Topical retinoids* – prescription creams formed from Vitamin A that help unclog pores and increase cell turnover
• Topical antibiotics – creams, lotions or gel pads that reduce inflammation by killing bacteria

Hyperpigmentation
Hyperpigmentation (Acanthosis nigricans) causes thickened, darkened skin patches that commonly affect the nape of the neck, armpits, skin under the breasts, and the groin. Insulin resistance causes this condition, which improves with adequate treatment of the underlying endocrine disorder. Treatment may include:
• Weight loss
• Dietary/pharmaceutical control of insulin resistance (such as Metformin)
• Topical exfoliants (e.g., lactic acid, tretinoin, urea-based medications)

Hair loss
Hair Loss (Androgenic alopecia) in women with PCOS is commonly due to a male hormone imbalance.
Treatments include:
• Minoxidil (Rogaine) – the only FDA-approved treatment for female pattern baldness, used topically on the scalp
• Anti-androgens* (Finasteride) – to counter the effects of the male hormone on hair loss

Excessive body weight
Approximately 50% of women with PCOS are overweight, due to an imbalance in caloric intake and caloric expenditure.
Management options include:
• Nutritional counseling – Individualized nutritional plans are created based on the patient’s preferences to ensure long-term compliance
• Physical activity counseling – Detailed assessment of patient’s lifestyle and individualized counseling to achieve optimal caloric expenditure
• Therapy – For certain patients, medical and/or surgical weight loss (bariatric surgery) and psychological counseling may be considered; treatment plans are individualized
* For women who are not pregnant and are not trying to get pregnant

Weight problems, cosmetic concerns, and distress regarding body image and infertility can be a source of tremendous stress for women with PCOS. Studies have identified that women with PCOS may be more likely to suffer from anxiety and depression. Chronic stress itself may contribute to some of the symptoms of PCOS (such as irregular menses) and be detrimental to fertility success. In recognition of the importance of the emotional component of PCOS, the Yale PCOS Program offers psychological support and counseling to complement medical, nutritional and lifestyle management strategies, and to help improve overall well-being in women of all ages diagnosed with PCOS. Psychological counseling options are available on site with our experienced counselor to help patients cope with:
• Menstrual irregularities
• Concerns related to self-image resulting from weight-related problems, acne, excessive body hair or hair loss
• PCOS-related infertility

Adolescents with PCOS may be especially prone to psychological and emotional distress from symptoms of PCOS. We offer a comprehensive program of psychological counseling and support for adolescents and their families to help cope with a PCOS diagnosis.

Signs and symptoms of polycystic ovarian syndrome (PCOS) can often be seen as a girl progresses through puberty. Although irregular menstrual cycles are part of the normal course of puberty, girls with PCOS are more likely to exhibit exaggerated symptoms such as:

• Irregular menstrual cycles for longer than a year
• Increased androgen production resulting in unwanted hair growth or scalp hair loss
• Increased body mass and insulin resistance
• Delay of more than two years between onset of puberty and occurrence of menses
• Early appearance of pubic hair prior to puberty
• Heavy uterine bleeding
• Acne
• Depression
• Weight gain

At the Yale PCOS Program, our medical practitioners include Ob/Gyns specializing in adolescent medicine. During a young woman’s first appointment, we strive to establish a physician/patient relationship that ensures the patient’s and family’s comfort and confidence in discussing any health issues and concerns. Discussions are individualized to the adolescent’s needs and include a review of:

• Normal pubertal development and menstruation
• Healthy eating habits and body image
• Preventive healthcare including the HPV vaccine and reproductive hygiene (including pregnancy and sexually transmitted infection prevention, if appropriate)
• PCOS-related concerns

Assessment of PCOS-related symptoms consists of a thorough medical evaluation, including a detailed medical history, nutritional assessment, physical examination, laboratory testing and an abdominal ultrasound (if appropriate). Treatment is individualized to the needs of each adolescent and tailored to her life stage. Similar to adult women, therapies for adolescents with PCOS include:

• Lifestyle modifications including diet and exercise to lessen the
symptoms of PCOS by improving insulin insensitivity and lipid levels, managing weight, and increasing self-esteem
• Birth control pills to regulate menstrual cycles and reduce androgen levels, which improves acne and excessive body hair, and may have a beneficial effect on overall body image
• Insulin sensitizing agents such as Metformin to lower insulin levels and improve metabolic problems associated with PCOS
• Anti-androgen treatments to decrease unwanted hair growth
when non-medical treatments are ineffective
• Psychological support for adolescents and families to help cope

Vitamin D: Sunlight Can Be Good for You

Evidence is growing that Vitamin D is crucial to many aspects of health—and that deficiency is extremely common, even in seemingly healthy people. The vitamin’s best-known role is in building bone, but low levels also appear to be associated with diabetes, heart disease, and infertility, among other diseases. “When you start looking at the data, the health benefits of D appear to be at every cellular level, in multiple organs,” said Lubna Pal, M.B.B.S., director of the Reproductive Aging and Bone Health Program.

Pal and her colleagues studied the health records of over 400 healthy pre-menopausal women and found that an astonishing 79% of them had low vitamin D levels. She found a link between low vitamin D levels and abnormal levels of blood sugar, insulin, inflammatory markers, and body mass. Such markers are associated with a higher risk of cardiovascular disease and diabetes. Women who were not Caucasian had lower levels of vitamin D, while more physically active women had higher levels.

In a previous study, Pal checked levels of vitamin D in the ovaries of 84 women undergoing fertility treatments. Almost two-thirds of the women had low levels, and those who achieved pregnancy had, on the average, higher levels of vitamin D than those who didn’t.

Vitamin D is made by the skin when touched by sunlight; it is also found in some foods. “We’re becoming more under-the-shade workers [and are] not getting our daily allowance,” said Pal. She suggests spending 10 minutes in the sun each day.

PCOS in Adolescents

Signs and symptoms of Polycystic Ovarian Syndrome (PCOS) can be seen during a girl’s pubertal transition. Although the normal pubertal course involves irregular menstrual cycles, increased androgen production, and increased body mass and insulin resistance, these processes are often exaggerated in girls with PCOS. A delay of greater than two years between the onset of puberty and the occurrence of menses may indicate PCOS. Furthermore, one early sign of PCOS may be the early appearance of pubic hair in young girls, prior to puberty. Adolescents with PCOS can present with a variety of symptoms which tend to start gradually, and can include irregular menstrual cycles, heavy uterine bleeding, acne, depression, weight gain, unwanted hair growth, or scalp hair loss.

One of the hallmarks of PCOS is irregular menstrual cycles. While it is normal for a young woman to experience irregular menstrual cycles for the first 6 to 12 months after her first menses, it is abnormal if the irregularity persists beyond 12 months. These young women deserve evaluation to determine a cause of their irregular cycles. In the past, young women were often prescribed oral contraceptives (birth control pills) to regulate their menstrual cycle, without any evaluation. However, due to the long-term health risks associated with PCOS, the ability to make this diagnosis in adolescents will hopefully improve the long-term health of these young women.

Similar to adult women, medical therapies for adolescents with PCOS include birth control pills, insulin sensitizing agents, and anti-androgen treatments. Treatment is individualized to the needs of each patient, and is tailored to where she is in her pubertal course.

Yale PCOS Program: A “One-Stop Shop” for Women with PCOS

Because Polycystic Ovarian Syndrome (PCOS) affects more than just the ovaries, Yale experts are teaming up to form a PCOS center for excellence. Clinicians at the Yale Program for PCOS will not only treat PCOS but also address problems that may accompany this diagnosis including fertility problems, body weight and body image issues, high cholesterol, insulin resistance and risk for diabetes, high blood pressure and risk for heart disease. The result will be what Dr. Pinar Kodaman, calls a “more holistic approach.”

“Beyond improving the overall health of women with PCOS, our goals are to help the patients take charge of PCOS,” says Dr. Lubna Pal, director of the Yale PCOS Program. During a single convenient appointment, patients will undergo evaluation by our team of expert physicians and nutritionists. Management strategies will be individualized to the needs of each patient. Risk profiles for heart disease and diabetes will be determined through detailed assessments, including tests that reflect the most advanced research into the disorder. Health goals will be identified (target weight, cholesterol, blood pressure, blood sugar, vitamin D level) and our team will work with each patient to ensure that these goals are met.

Each of the Yale Ob/Gyn physicians at the Yale PCOS Program brings her own expertise to the table:
Adolescents and teenagers with symptoms of PCOS (such as menstrual irregularities, excessive facial and body hair and acne) will benefit from Dr. Beth Rackow’s expertise in adolescent gynecology and menstrual disorders.

Utilizing combinations of lifestyle modifications and medications, Dr. Kodaman will focus on reducing risks for cardiovascular disease while Dr. Pal concentrates on issues of insulin resistance and diabetes.

Dr. Stephen Thung, a Yale Maternal-Fetal Medicine specialist with a special interest in the management of gestational diabetes and hypertension in pregnancy (common in women with PCOS), joins the team as a resource for preconception consultation for patients deemed at high risk for pregnancy-related problems.

Amy Krystock, a registered dietitian, employs a total lifestyle modification approach, utilizing customized diet and exercise programs for women with PCOS.

Dorothy Greenfeld, LCSW, provides an invaluable resource for psychological support, helping patients overcome the stress of PCOS symptoms and diagnosis.

By combining our efforts and expertise, we hope to be able to address the health needs of women of all ages diagnosed with PCOS. “I can foresee a teenager with PCOS being cared for at our center through her reproductive years into menopause,” says Dr. Pal.