Polycystic Ovary Syndrome Research Program

PCOS which may also be referred to as polycystic ovary disease (PCOD) is the most common hormonal disorder found in premenopausal women. PCOS affects 7% of women from all races and nationalities. Typically, PCOS symptoms first appear in adolescence, normally around the start of menstruation. Occasionally, some women do not develop PCOS symptoms until their early to mid-20s. One of the most common symptoms of PCOS is irregular periods.

Although the cause of PCOS is unknown, women with PCOS have high male hormone levels, which can lead to acne, extra facial and body hair, and irregular periods. Additionally, PCOS is the leading cause of hormonal infertility.

Other symptoms associated with PCOS are the heart disease risk factors of weight gain, cholesterol problems, high blood pressure, insulin resistance and diabetes. PCOS may also increase the risk of developing endometrial cancer.

What is understood is that PCOS is an inherited disease. Sisters and daughters of women with PCOS are at high risks themselves of developing PCOS. In addition, both female and male relatives have an increased risk of getting diabetes and heart disease.

Keep it Simple: What Endos Really Need to Know about PCOS

 

PCOS is called a syndrome rather than a disease because there are such a variety of symptoms. No two women have exactly the same symptoms. The following characteristics are very often associated with PCOS, but not all are seen in every woman:

  • Hirsutism: Excess hair growth on the face, chest, abdomen, thumbs, or toes.
  • Acne/oily skin: In women with PCOS, oil production is stimulated by overproduction of male hormones.
  • Thinning hair PCOS can cause androgenic alopecia--scalp hair loss--in a classic “male baldness” pattern.
  • Acanthosis nigricans Dark patches of skin velvety or rough to the touch most commonly seen on the back of the neck, but also in skin creases in other areas.
  • Polycystic ovaries: Ovaries have a “string of pearls” or “pearl necklace” appearance with many cysts (fluid-filled sacs).
  • Obesity or weight gain:
  • Infertility or reduced fertility: Because women with PCOS do not ovulate regularly, it affects their ability to conceive.
  • Menstrual irregularities: Less than 8 periods per year or lengthy bleeding episodes, scant or heavy periods, or frequent spotting.

Because symptoms like acne and obesity have multiple causes, PCOS is often mistaken for another condition. Despite its name, some women with the syndrome do not have detectable ovarian cysts, whereas many women without PCOS do.

Women with PCOS have an increased risk of developing a number of other health conditions.

Type 2 diabetes: Women with PCOS are predisposed to a pre-diabetic condition and an increased chance for diabetes later in life. These are conditions which involve problems regulating blood sugar in the body.

Insulin resistance: Insulin resistance is a condition where the body’s use of insulin is inefficient. It is usually accompanied by an over-production of insulin.

Lipid abnormalities: Some women with PCOS have elevated LDL and reduced HDL cholesterol levels, as well as high triglycerides.

Cardiovascular disease: Women with PCOS face an increased cardiovascular risk due to a variety of reasons including obesity, hypertension, and blood lipid abnormalities.

Endometrial cancer (cancer of the uterine lining): This risk comes from lack of menstruation. Women who have not reached menopause and are not having periods on their own on a semi-regular basis, may be at risk for developing endometrial cancer.

Though the exact cause and course of development of PCOS are still unknown, research has shown that several of the symptoms develop as a result of hormonal imbalance. This imbalance seems to be linked with the way the body produces insulin, the hormone that helps cells absorb sugar from the bloodstream.

PCOS women do not respond properly to insulin; when they eat a meal, the insulin released by the pancreas is not enough to move glucose into the cells where it belongs, so the body continues to produce more of the hormone. The production of extra insulin stimulates the ovaries to produce excess androgens (male hormones, such as testosterone).

Elevated androgen levels may prevent the ovaries from releasing an egg each month, causing the formation of small, painless cysts on the ovaries as well as infertility. High androgen levels in women are also responsible for the many PCOS symptoms that women experience, including irregular menstrual cycles, hirsutism (excess hair), acne, weight gain, thinning hair, depression, anxiety, and skin problems.

Besides elevated androgen levels and its related symptoms, PCOS is also associated with insulin resistance. With insulin resistance, the body is able to make insulin; however, it cannot respond to it, causing high levels of insulin to remain in the blood stream, putting women with the syndrome at increased risk for developing Type 2 diabetes as well as heart disease.

PCOS can be difficult to diagnose because women experience the syndrome to varying degrees. However, there are several methods a physician can use to determine if you have PCOS. Your doctor will begin by obtaining your medical history, especially relating to your menstrual cycles, and performing a physical exam.

Often blood tests are done to help identify any abnormal hormonal levels, particularly increased testosterone levels.

An ultrasound may be performed to determine if there are multiple cysts on the ovaries or if the ovaries are enlarged. However, this test is not necessary for the diagnosis.

If menstrual periods have been irregular or absent for a long period of time, an endometrial biopsy may be necessary to evaluate the endometrium and rule out pre-cancerous cells. This procedure involves taking a sample of the endometrium and examining it under a microscope. Your physician will also try to rule out other possible causes of irregular menstruation and excessive hair growth, such as Cushing’s syndrome, congenital adrenal hyperplasia, or other disorders of the pituitary or adrenal glands.

Your doctor also may test your insulin and glucose levels to look for diabetes or insulin resistance (inefficient use of insulin in the body).

An oral glucose tolerance test gives the doctor information about how your body uses sugar (glucose). After an overnight fast (10-12 hours), you will be asked to drink a sweet solution containing a known amount of glucose. Blood is drawn before you drink the glucose solution, and again two hours after the drink is finished to see how your body was able to use the glucose. Although the test is complete in two hours, you should plan to be at your doctor’s office for three hours to allow time for preparation.

Used with permission by A. Dunaif.

Since PCOS is not a disease per se, treatment is targeted more towards prevention of long-term problems such as diabetes and heart disease as well as towards managing symptoms. You and your doctor will work together to decide how to best treat and manage your condition. Some of these treatments include:

Birth control pills: Oral contraceptives contain female hormones that can help treat the problem of irregular menstrual cycles and lower levels of androgens (male hormones).

Insulin-sensitizing medications: Since there is a close connection between PCOS and diabetes, some women have been successful at treating their PCOS symptoms with medications used to treat diabetes. Metformin (Glucophage) is often prescribed by doctors to help the body use insulin more effectively, thus lowering insulin levels. Insulin-sensitizing medications have also been shown to help lower androgen levels and establish a regular menstrual cycle.

Infertility: For women who are concerned with fertility and are trying to get pregnant, certain hormone treatments can be used to induce ovulation. One common medication is clomiphene citrate (Clomid, Serphene, Milophene).

Overweight: A healthy diet, particularly limiting manufactured carbohydrates (cereals, breads, pastas), is recommended. Manufactured carbohydrates may be replaced with healthier carbohydrates such as whole grains, fruits, and vegetables. Also, your diet should include enough protein to control the amount of sugar in your blood.

Even a small amount of weight loss can significantly reduce PCOS symptoms and the risk of diabetes and heart disease. Daily physical activity can help the body use insulin better and help you to lose and keep off weight.

Excessive hair growth: Several methods can be used to physically remove or lighten excess hair. Methods like shaving, chemical depilation, waxing, bleaching, electrolysis, laser hair removal and creams like eflornithine (Vaniqua) can be tried. These methods can be used in conjunction with medications like birth control pills and anti-androgens like spironolactone (aldactone).

Scalp hair loss: To treat thinning hair, minoxidil (Rogaine) and spironolactone (aldactone) are sometimes used in women with PCOS. Hair weaves, extensions, and even surgical treatment are other solutions for women with serious hair loss. Surgical options include hair transplantation and scalp reduction.

Acne: Treatments sold over the counter can help control skin blemishes that can arrive with PCOS.

There is no cure for PCOS; however, a growing number of women with the condition are now being treated with medication to help them manage the symptoms as well as the long-term effects of the condition. Your doctor may prescribe the following medications:

  • Metformin (Glucophage): This medication is used primarily to help control blood glucose levels in people with Type 2 diabetes. While it does offer benefits to women suffering from PCOS, the drug is not FDA-approved for the treatment of the condition. Studies indicate metformin reduces insulin, testosterone, and glucose levels -- which helps to reduce acne, hirsutism, abdominal obesity, amenorrhea, and other PCOS symptoms. Some of the common side effects of metformin are nausea, vomiting, and diarrhea, which usually subside after several weeks on the medication. Side effects can be minimized by taking the medication with meals and increasing the dose gradually over a period for weeks, as prescribed by a doctor. Individuals who become dehydrated, are hospitalized, or need to have an IV contrast test, should discontinue use of this medication.
  • Spironolactone (Aldactone®): This medicine was originally developed to treat certain forms of high blood pressure. In high doses (75-200 mg per day), it is very effective in treating excess hair growth due to male hormone elevations. It may also be helpful in slowing hair loss due to male hormone elevations. It also decreases skin oiliness and acne. It is not FDA-approved for the treatment of male hormone elevations.
  • Decreases in skin oiliness and acne can be seen after 1 to 2 months of treatment with spironolactone. The rate of excess hair growth will slow and the hair will become finer and lighter; becoming much less noticeable. The hair, however, will not fall out. Maximum benefits might not be seen until one year of therapy and hair growth will resume if therapy is discontinued. In women with hair loss, it often takes approximately one year to notice a benefit from therapy. Usually, further hair loss is arrested. It is uncommon to see re-growth of hair that has already been lost.
  • Spironolactone has few side effects. If it is not given in combination with an oral contraceptive agent, it can cause irregular vaginal bleeding. Because spironolactone blocks male hormones, it is essential that it not be taken by women who are pregnant because it can interfere with sexual development of a male fetus. If you think you might be pregnant, DO NOT take spironolactone. If you are not on oral contraceptive agents, you must use an effective birth control method while on spironolactone. Spironolactone may cause elevations in serum potassium levels; therefore, women taking the medication should not take supplemental potassium.
  • In animal studies with high doses of spironolactone, certain tumors developed. Therefore, long-term therapy with the drug is not recommended. Every several years, the need for spironolactone treatment should be reassessed.

Multiethnic Fine-Mapping of PCOS Genetic Variants 

  • Follow-up study to our recent GWAS publication
  • Women between the ages of 18 – 40 
  • Involves completion of a brief questionnaire and single blood draw
  • Receive $75 gift card upon completion  

If interested, please complete the survey: PCOS Study Eligibility Survey 

For more information, or for any questions, please call (212) 241-0515 or email PCOS@mssm.edu

 

If you think you have PCOS or if you have been diagnosed with PCOS, continue to read and learn all you can to manage your symptoms. More information about PCOS is available through:

Andrea Dunaif, MD, is a Professor of Medicine, Endocrinology, Diabetes and Bone Disease, and Chief, Division of Endocrinology, Diabetes and Bone Disease. Her research has been at the forefront of studies on the genetic basis of PCOS. She demonstrated that hyperandrogenemia was the cardinal reproductive phenotype in PCOS families and has mapped several genetic susceptibility loci associated with this phenotype. Dr. Dunaif was the first to show that male and non-reproductive-age female relatives of women with PCOS have reproductive and metabolic phenotypes. Most recently, she has extended this work to show that premenarchal girls and infants have reproductive and metabolic phenotypes, including evidence that they are already at high risk for type 2 diabetes. Her team has recently completed two genome-wide association studies to identify genetic loci associated with PCOS and its quantitative traits in women with PCOS of European and Han Chinese ancestry. She has mapped the first replicated genetic locus for PCOS as a variant within the fibrillin-3 gene.  She is the Principal Investigator for the study.

Sherley Abraham, MD, is an Assistant Professor in the Division of Endocrinology, Diabetes and Bone Disease at Icahn School of Medicine at Mount Sinai. Dr. Abraham is a scientist and clinician with broad experience in healthcare and academic medicine. She is board certified in Endocrinology, Diabetes, and Metabolism as well as Internal Medicine.  After graduating from the SUNY Stony Brook School of Medicine, she completed her Residency at the NYU School of Medicine. Dr. Abraham then completed a Fellowship in Hypertension and Lipidology in the Physician-Scientist Training Program at the NYU School of Medicine followed by a Fellowship in Endocrinology, Diabetes, and Metabolism at the Johns Hopkins University School of Medicine. She is an experienced clinician and is assisting in the recruitment and study of PCOS cases and controls. 

Ron Do, PhD, is an Assistant Professor, Department of Genetics and Genomic Sciences at Icahn School of Medicine at Mount Sinai. His research focuses on the genetic and biological bases of coronary artery disease and cardiometabolic risk factors. He has formal training in human genetics, statistical genetics and population genetics. Dr. Do has expertise in human genetics, genetic epidemiology, statistical genetics, population genetics and analysis of large-scale sequencing and genotyping datasets. He plays a critical role in prioritization of the PCOS susceptibility loci to be sequenced, the design of the sequencing analysis, and selection of variants for genotyping and the review of all data analyses.

Dori Arad, PhD, RDN, CDN, CDE, EP-C,
is a research associate in the Division of Endocrinology, Diabetes and Bone Disease. Dr. Arad has an expertise in nutrition, physiology, and metabolism and his research focus on obesity and diabetes. Specifically, assessing metabolic function in individuals with and at risk for type 2 diabetes. Under the guidance of Dr. Dunaif, Dr. Arad is organizing the clinical part of the Multiethnic Fine Mapping of Polycystic Ovary Syndrome study. 

Alina Rahimova, MD, MS , is a Bioinformatician in the Division of Endocrinology, Diabetes and Bone Diseases at Icahn School of Medicine at Mount Sinai. Dr. Rahimova is an Endocrinologist with 8 years of experience both in clinical and research fields,with particular interest in Pediatric Endocrinology. She started her career in Biomedical Informatics after graduating from NYU School of Medicine’s Sackler Institute of Graduate Biomedical Sciences. Under supervision of Dr. Dunaif in the PCOS study, she manages and integrates knowledge from prior experiments and biological databases through existing and novel algorithms (Machine Learning, NLP).

 

 

 

Pathogenic Anti-Müllerian Hormone Variants in Polycystic Ovary Syndrome.
Gorsic LK, Kosova G, Werstein B, Sisk R, Legro RS, Hayes MG, Teixeira JM, Dunaif A, Urbanek M. J Clin Endocrinol Metab. 2017 Aug 1;102(8):2862-2872. doi: 10.1210/jc.2017-00612. PMID:28505284 ISSN PMCID: PMC5546867 ISSN: 0021-972

Exaggerated glucagon responses to hypoglycemia in women with polycystic ovary syndrome.
Sam S, Vellanki P, Yalamanchi SK, Bergman RN, Dunaif A
Metabolism: Clinical and Experimental. 2017 Jun; 71: 125-131. doi:http://dx.doi.org/10.1016/j.metabol.2017.03.008.
PMID: 28521865 PMCID: 28521865 ISSN: 0026-0495

Delayed diagnosis and a lack of information associated with dissatisfaction in women with polycystic ovary syndrome.
Gibson-Helm M, Teede H, Dunaif A, Dokras A
Journal of Clinical Endocrinology and Metabolism. 2017 Feb; 102(2): 604-612. doi:http://dx.doi.org/10.1210/jc.2016-2963.
PMID: 27906550 ISSN: 0021-972 

Polycystic ovary syndrome
Azziz R, Carmina E, Chen Z, Dunaif A, Laven JSE, Legro RS, Lizneva D, Natterson-Horowtiz B, Teede HJ, Yildiz BO. Nature Reviews Disease Primers. 2016 Aug 11; 2: doi:http://dx.doi.org/10.1038/nrdp.2016.57.
PMID: 27510637 

Increased antimüllerian hormone levels and other reproductive endocrine changes in adult male relatives of women with polycystic ovary syndrome
Torchen LC, Kumar A, Kalra B, Savjani G, Sisk R, Legro RS, Dunaif A
Fertility and Sterility. 2016 Jul; 106(1): 50-55. doi:http://dx.doi.org/10.1016/j.fertnstert.2016.03.029.
PMID: 27042970 PMCID: 27042970 ISSN: 0015-0282

Genetic Variants in DENND1A May Affect Reproductive, Metabolic Profiles in PCOS 

International sports authority enforces controversial eligibility rule for female athletes (Healio)

Male-Hormone Gene May Help Cause Polycystic Ovary Syndrome (Health Day)

Male-Hormone Gene May Help Cause Polycystic Ovary Syndrome (U.S. News & World Report)  

1st Gene Linked to Polycystic Ovary Syndrome (WebMD) 

Half of all women with PCOS share a rare gene variant (News Medical & Life Science) 

Male-Hormone Gene May Help Cause Polycystic Ovary Syndrome (Doctors Lounge) 

PCOS Traits Tied to Rare Variants in Testosterone-Related Gene (GenomeWeb) 

Researchers identify causes and mechanisms of polycystic ovary syndrome using family-based genetic analysis (Medical Xpress) 

Male Hormone Production Causes Polycystic Syndrome: Doctors (The Downey Gazette)

Mount Sinai Researchers Identify Causes and Mechanisms of Polycystic Ovary Syndrome Using Family-Based Genetic Analysis (Yahoo! News) 

Family-based quantitative trait meta-analysis implicates rare noncoding variants in DENND1A in polycystic ovary syndrome (Journal of Clinical Endocrinology & Metabolism)

Researchers Identify Causes and Mechanisms of Polycystic Ovary Syndrome Using Family-Based Genetic Analysis (Icahn School of Medicine at Mount Sinai) 

Half Of Women With Polycystic Ovary Syndrome Have Rare Variants Of A Common Gene (IFL Science)

Hope for women with incurable ovary condition: Scientists discover gene behind the main cause of female infertility - paving the way to treatment (Daily Mail)   

https://www.medscape.com/viewarticle/910940

Hormone levels may predict PCOS in premenarchal girls

New international sports rules concerning women’s hormone levels raise competitive, ethical concerns

Can Your Androgen Excess Give You an Edge?

Bustle – August 13 

Women With PCOS Are More Likely To Feel Unhappy With Their Doctors, Study Finds — Mariella Mosthof
A recent study in the Journal of the Endocrine Society found that PCOS patients are more likely to be unhappy with their medical care than their non-PCOS-suffering counterparts. PCOS, short for Polycystic Ovary Syndrome, is characterized by ovaries enlarged with an unusual number of follicles, irregular periods, and hormonal side effects like acne, excess body hair, and obesity. Frequently, doctors only arrive at a PCOS diagnosis when they’ve ruled out everything else. “When patients say they argue with their physicians, I think the arguments are based on the fact that they have become more knowledgeable than their physicians in this area,” said Andrea Dunaif, MD, chief of the division of endocrinology, diabetes and bone disease at the Mount Sinai Health System. She surmises that patients are often put in the position of self-diagnosing using the internet. Thanks to the so-called "research gap," women's pain is often ignored, minimized, or dismissed by physicians. – Andrea Dunaif, MD, Chief, Division of Endocrinology, Diabetes and Bone Disease, Mount Sinai Health System

Learn more: https://www.bustle.com/p/women-with-pcos-are-more-likely-to-feel-unhappy-with-their-doctors-study-finds-10064744  

 

Newsmax Health – August 5

Women With Common Ovary Condition Often Feel Medical System Failed Them
Many women with polycystic ovary syndrome feel they've been let down by a healthcare system that takes years to diagnose their condition, a new survey suggests. Researchers found that women with polycystic ovary syndrome, or PCOS, a common condition characterized by metabolic and fertility problems, were more likely than others to distrust their primary care physician's judgment and to feel that they weren't getting enough social support from healthcare providers. A contributor to delayed diagnoses may be primary care physicians’ lack of familiarity with the condition, not to mention the latest information on it, said Andrea Dunaif, MD, chief of the division of endocrinology, diabetes and bone disease at the Mount Sinai Health System. The name, which is really a misnomer, doesn't help, Dr. Dunaif said. The bumps on the ovaries aren't cysts and the condition has symptoms that go far beyond the reproductive system, she explained. PCOS has also been linked to increased risks for diabetes, obesity and heart disease. Dr. Dunaif has a piece of advice for primary care physicians. "Menses are a vital sign," she said. "You should be asking women what their menstrual history is. It can be a sign that there is an endocrine disorder that needs to be diagnosed." – Andrea Dunaif, MD, Chief, Division of Endocrinology, Diabetes and Bone Disease, Mount Sinai Health System 

Learn more: https://www.newsmax.com/health/health-news/women-polycystic-ovary-syndrome-pcos/2018/08/05/id/875574/  

Additional coverage: 

Physician’s Weekly https://www.physiciansweekly.com/women-with-common-ovary/  

Deccan Chronicle https://www.deccanchronicle.com/lifestyle/health-and-wellbeing/040818/women-with-common-ovary-condition-often-feel-medical-system-failed-the.html