Medical Professionals in Infertility - Fertility CARE

Polycystic Ovarian Syndrome: New approaches to an old problem.

Mark P. Trolice, M.D., FACOG, FACS
Board Certified, Reproductive Endocrinology and Infertility
Director, Fertility C.A.R.E.

Polycystic Ovarian Syndrome (PCOS) is the most common endocrine abnormality in reproductive-aged women affecting approximately 5-10% of this population. The classic triad of this syndrome consists of chronic anovulation, hirsutism and obesity. The exciting news recently involves understanding the contribution of insulin resistance to the etiology and treatment of PCOS.

For more information, read : Polycystic Ovarian Syndrome and Insulin Resistance.

PCOS, a definition

PCOS involves a "vicious cycle" of hormonal imbalance that may begin with a hypersensitivity of the pituitary to GnRH. The pituitary responds with an increase in LH secretion resulting in increased ovarian androgen production by the ovarian thecal cells. Consequently, FSH production is inhibited thereby further preventing follicle development and ovulation.

Additionally, estrone proliferates the endometrium unopposed and increases the risk of endometrial hyperplasia and possibly cancer. To summarize, PCOS is perpetuated by tonic elevations of LH resulting in hyperandrogenemia and chronic anovulation.

PCOS can be diagnosed clinically in women who present with oligomenorrhea (menstrual intervals >35 days), hyperandrogenism and obesity (after ruling out other endocrine disorders).

However, most women with PCOS do not exhibit all of these features and there is a considerable controversy about the definition and required criteria for the diagnosis. The minimal criteria include chronic anovulation and hyperandrogenism, and the diagnosis may include pelvic ultrasound to evaluate morphology for PCOS "appearing" ovaries.

The clinical presentation and medical consequences of PCOS include:

  • Infertility
  • Abnormal uterine with the risk of endometrial hyperplasia
  • Hyperandrogenism
  • Obesity
  • Insulin resistance with the risk of impaired glucose tolerance and diabetes. (Insulin resistance is a key finding in the "metabolic syndrome" along with elevated cholesterol, triglycerides, blood pressure, and waist circumference.)

Evaluation of The Condition

Polycystic ovary syndrome is primarily a clinical diagnosis, and laboratory findings should only be used to support the clinical testing and rule out other serious disorders. Evaluation should include:

  • Measurement of thyroid-stimulating hormone (TSH), prolactin, and in some cases, morning 17alpha hydroxyprogesterone to rule out late-onset adrenal hyperplasia.
  • Patients, regardless of age, with a greater than 3 month menstrual intervals and/or an endometrial thickness of >= 7mm on ultrasound should undergo an endometrial biopsy due to the risk of hyperplasia.
  • Insulin resistance can best be evaluated by a 2-hour glucose tolerance test (GTT).

Management of PCOS

Weight reduction, diet and exercise are recommended for all women with PCOS. Some studies have also shown a 5-10% loss in body weight may result in a return of ovulatory cycles and a higher spontaneous pregnancy rate.

Monthly progestin therapy can be used to prevent abnormal endometrial proliferation by inducing withdrawal bleeding.

Another option for these women is to use low dose oral contraceptive pills (OCP) to regulate the menstrual cycle and provide contraception. Antiandrogens may be combined with oral contraceptive pills for the treatment of hirsutism and acne.

Approximately 80% of women with PCOS ovulate in response to clomiphene, but only about 50% of them become pregnant.

In patients desiring pregnancy, ovulation induction is often required usually with clomiphene citrate. Approximately 80% of women with PCOS ovulate in response to clomiphene, but only about 50% of them become pregnant.

Most recently, the aromatase inhibitor letrozole has been shown to have equal success as clomiphene with ovulation but less of a negative impact on endometrial proliferation. (Of note, this is a non -FDA approved use of letrozole but no evidence of teratogenicity to date.)

Insulin resistance has been implicated in the reproductive consequences of PCOS, namely infertility, miscarriage, and gestational diabetes. Multiple studies have supported the use of metformin to ameliorate these problems. The dose and duration of metformin has not been determined and there has been no definitive evidence for teratogenicity.

Ovarian surgery has been an effective therapy for patients resistant to clomiphene citrate and/or letrozole. Laparoscopy with bilateral ovarian diathermy involves "drilling" holes in the ovarian stroma utilizing electrocautery or laser providing an approximate 84% ovulation induction rate and 56% pregnancy rate with maintenance of ovulation demonstrated for up to 20 years in the majority of patients.

In Summary

PCOS is a chronic condition that can be successfully managed with close surveillance. Approaches are directed at preventing potential long-term consequences of chronic anovulation (abnormal uterine bleeding and endometrial hyperplasia), the metabolic abnormalities associated with the syndrome (insulin resistance and diabetes), treating infertility, as well as improving the external manifestations of hyperandrogenism (hirsutism and acne).