January 2019, Volume XXXIII, No 10

Women’s Health

Polycystic ovary syndrome

Diagnosis and treatment

ome five million women of childbearing age in the United States struggle with polycystic ovary syndrome (PCOS), leading to an annual price tag of $4 billion for PCOS identification and management, as reported by the National Institutes of Health’s Office of Disease Prevention.

The most common hormone disorder among women of reproductive age, PCOS presents varying clinical and biochemical features, including hyperandrogenism and ovulatory dysfunction. With symptoms that include irregular or absent uterine bleeding, infertility, hirsutism, chronic acne, obesity, insulin resistance, and Type 2 diabetes, PCOS can particularly impact women hoping to conceive, just one of the reasons that early detection is crucial. Even women on the mild end of the spectrum of PCOS symptoms can have severe underlying metabolic changes that increase overall health risks.

Debates on overdiagnosis

There has been some recent discussion in the medical community and literature that the Rotterdam Criteria—three indications of potential PCOS, described below—should be revised, because they may lead to overdiagnosis of the condition. Other commentators question the potential psychological impacts on young women being labeled as having a “disorder” following a possible misdiagnosis. At the same time, many of the patients I have diagnosed with PCOS were told by earlier providers that they were simply “obese” or “insulin resistant,” with no consideration of the underlying PCOS diagnosis/etiology.

Given the risks of PCOS, particularly among women of reproductive age, I personally believe that each patient that presents with possible features of PCOS should receive a proper work-up of said symptoms and a thorough diagnosis. It is also important to have differential diagnoses of other potential endocrine disorders (thyroid disease, pituitary disfunction, premature ovarian failure, etc.)

[PCOS is] the most common hormone disorder among women of reproductive age.

While there are psychological impacts on women being labeled as “sick” or having a “disease,” there is equal emotional impact on not feeling well or knowing something is “wrong” but not having an explanation. These women get labeled as obese, diabetic, or hypertensive, and are told to improve these conditions. In my opinion, this also can cause poor self-esteem and body image and can increase anxiety and depression symptoms.

Once a woman gets an explanation of the underlying processes in her body causing PCOS and these symptoms, she can gain a better understanding of her health and be motivated to make the right changes to see improvements. In my experience, the proper diagnosis and treatment of PCOS can be life-changing for women as they take ownership of their own bodies and health.

PCOS and the pregnancy journey

Due to its varying degrees of biochemical dysfunction, polycystic ovary syndrome can have a wide range of symptoms and associated risks, with infertility serving as one of the most recognized difficulties. Not only do the symptoms of PCOS make it more difficult to achieve pregnancy, but those who do become pregnant may face additional complications, including increased rates of spontaneous abortion in the first trimester, gestational diabetes, and pregnancy-inducted hypertensive disorders such as preeclampsia—all of which add up to increased rates of pre-term delivery in women with PCOS.

Some women don’t know they have polycystic ovary syndrome until they try to conceive and struggle to get pregnant. Some patients aren’t concerned about irregular periods up until this point or don’t realize their cycles are abnormal since that has been their experience since menarche. For this reason, an annual discussion with your female patients about their menstrual cycles is essential. Cysts on the ovaries and elevated androgen hormones can prevent ovulation or make it irregular, so many women require some sort of treatment and sometimes medication to help promote regular ovulation. If pregnancy is achieved, careful monitoring of early pregnancy viability, screening for gestational diabetes, and monitoring of blood pressure are imperative. Pre-pregnancy awareness, treatment interventions, and preparation can help lead to a healthier pregnancy and delivery in women with PCOS.

Pinpointing a PCOS diagnosis

Beyond the clinical symptoms of PCOS, labs can indicate elevated androgen levels in the blood, while ultrasound imaging may reveal polycystic ovaries.

When evaluating a patient with possible PCOS, physicians should consider the following three criteria; adults need two of the three criteria to receive a PCOS diagnosis:

  1. Clinical or laboratory evidence of hyperandrogenism, which can be clinically characterized by severe acne, hirsutism, or male-pattern hair loss;
  2. Evidence of oligo/anovulation—irregular or absent menstrual cycles;
  3. Ultrasound evidence of at least one polycystic ovary, with an ovarian volume greater than 10 cubic centimeters or the presence of 12 or more follicles, each measuring between two to nine millimeters in diameter.

When a patient displays all three of these Rotterdam Criteria, she is determined to have “classical PCOS,” or Phenotype 1. On the other hand, women with only two of the criteria are determined to have:

  • Phenotype 2, characterized by hyperandrogenic anovulation (criteria 1 and 2);
  • Phenotype 3, or ovulatory PCOS (criteria 1 and 3);
  • Phenotype 4, or non-hyperandrogenic PCOS (criteria 2 and 3).

Regardless, all polycystic ovary syndrome symptoms can be improved with a unified treatment approach. The goals include alleviating the bothersome symptoms of hyperandrogenism, managing the underlying metabolic abnormalities to reduce the risk of cardiovascular disease/Type 2 diabetes, preventing endometrial hyperplasia, and achieving pregnancy for women wishing to conceive (or providing reliable contraception, since sporadic ovulation can lead to unplanned pregnancies).

Early diagnosis can be critical to a woman’s health. Beyond infertility, other concerns include metabolic syndrome, obstructive sleep apnea, cardiovascular disease, increased risk of endometrial cancer, and other notable issues. Recent studies indicate that women with PCOS are also at increased risk for anxiety and depression. Symptoms can commonly be mistaken for other hormone abnormalities, including thyroid disorders, so it is important to discuss a woman’s full range of symptoms in addition to a physical exam, ultrasound, and lab work when polycystic ovary syndrome is a possibility.

The exact cause of PCOS remains unknown.

A combination approach to treatment

Typically, a combination of lifestyle changes and medications come together in a successful PCOS treatment plan to manage symptoms and prevent worsening of the outcomes of PCOS.

Weight loss alone, for example, can restore regular ovulatory cycles and decrease metabolic risks, so this is often the first line and most important treatment modality, when applicable. Women who are significantly overweight have been found to resume regular menstrual cycles after losing just 5% to 10% of their body weight. While a low-carb, high-fat diet mixed with periods of intermittent fasting may be the most successful for women with PCOS, according to some studies, typically the best option is whatever is sustainable for an individual over the long term. Regular exercise and healthy eating, regardless of the specific diet plan, can lower blood pressure and cholesterol levels and decrease the risk of diabetes and heart disease, and should be encouraged for all women with polycystic ovary syndrome. At a new diagnosis of PCOS, I typically refer my patients for additional education in this area with a dietician or functional medicine provider who can help guide them with individual lifestyle plans that focus on the most natural ways to help improve their symptoms through dietary changes and the addition of appropriate vitamin/nutritional supplements.

In addition, combined hormonal (estrogen-progestin) oral contraceptives (CHCs) are the first-line medication therapy, if there are no contraindications for the patient. The Centers for Disease Control and Prevention’s U.S. Medical Eligibility Criteria for Contraceptive Use can help physicians determine potential contraindications in certain patients. Contraceptives can help patients manage hyperandrogenism symptoms while supporting menstrual regularity and contraception, if desired. Aim for a pill with at least 20 mcg of ethinyl estradiol and a progestin with lower androgenicity, such as norethindrone or norgestimate. If patients continue to struggle with acne or other hyperandrogenic symptoms after six months on that contraceptive, you can consider adding in an antiandrogen, such as spironolactone at 50–100 mg twice per day.

Finally, a referral to an obstetrician/gynecologist can help to support women with polycystic ovary syndrome who are interested in becoming pregnant. Ovulation induction protocols can be effective for women hoping to conceive, including the use of letrozole, which has been shown to have higher pregnancy outcomes in women with PCOS as opposed to the previously well-used clomiphene citrate. A majority of my patients with PCOS are able to achieve successful pregnancy with oral ovulation induction protocols or continuing care with a reproductive endocrinologist for more aggressive fertility treatments, including possible in vitro fertilization, if necessary.

Research into PCOS remains ongoing

While the exact cause of PCOS remains unknown, it appears to arise from a complex interaction of genetic and environmental factors. Some researchers believe it is similar to the “two-hit” hypothesis of cancer manifestation: Women with the underlying congenital predisposition for hyperandrogenic production have one “hit,” which can lead to polycystic ovary syndrome when it is combined with a second “hit” such as metabolic syndrome, obesity, or insulin resistance.

Researchers continue to study specific genes that may be involved in polycystic ovary syndrome. Some recent findings focus on polymorphisms, linkages, and differential expression of gene encoding as well as other potential players in the development of PCOS, such as steroidogenic enzymes, sex hormone-binding globulin, the androgen receptor, transcription factors, gonadotropins and gonadotropin receptors, genetic variants associated with insulin sensitivity and susceptibility to obesity, and congenital adrenal hyperplasia. However, it remains unclear how such factors are specifically related to the development of PCOS, again pointing to the combination of genetic and environmental factors that can impact a woman’s health.

While polycystic ovary syndrome has traditionally been studied more extensively in adults, further clinical interest is arising in PCOS among adolescents, especially as rates of childhood obesity increase. Since a PCOS diagnosis can take years, most women are diagnosed with the syndrome in adulthood, but it is worth paying attention to the potential for polycystic ovary syndrome in your younger patients as well.

Regardless of age, early and accurate diagnosis are critical to a woman’s ability to conceive later in life and her overall health. Ultimately, the silver linings to the challenge of PCOS are that we are now better than ever at diagnosing polycystic ovary syndrome and can help patients achieve greater comfort and outcomes while research into the matter is now taking place on a constant, ongoing basis.

Amy Hammers, MD, sees patients at the Maple Grove location of Clinic Sofia, an OBGYN clinic known for its personalized approach to women’s health care. A graduate of Creighton University School of Medicine, she is a member of the American College of Obstetrics and Gynecology, the American Institute of Ultrasound in Medicine, and the American Medical Association. 

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Amy Hammers, MD, sees patients at the Maple Grove location of Clinic Sofia, an OBGYN clinic known for its personalized approach to women’s health care. A graduate of Creighton University School of Medicine, she is a member of the American College of Obstetrics and Gynecology, the American Institute of Ultrasound in Medicine, and the American Medical Association.