Clinical:Case Study: Polycystic Ovarian Syndrome

Original materials created in April 2000 by Justina Trott, M.D.

Polycystic Ovarian Syndrome

(PCOS) is the most common endocrine disturbance affecting women. The name PCOS is misleading and minimalistic, paralleling the history of health care for women in general in its focus on the reproductive organs rather than whole body. Cystic abnormalities of the ovaries were originally described by Chereau in the mid 19th century. In 1935, Stein and Leventhal described a syndrome of ammenorrhea, infertility, and hirsutism associated with bilaterally enlarged, cystic ovaries. Subsequently it was noted that there was increased production of androgens and the etiology of the overproduction was presumed to be the enlarged ovaries or disturbances of the hypothalamic-pituitary- ovarian axis. For this reason PCOS has been managed by OB/GYN physicians, their therapeutic armamentarium being reproductive hormonal manipulation. Emphasis on women’s reproductive function as distinct from the physiologic environment in which the reproductive organs exist has blinded us to the complexity and interrelatedness of the entire endocrine system, including the neuro-endocrine axes. In the past 1-2 decades a clearer understanding of PCOS has allowed for different therapeutic interventions, which have potential not only to treat symptoms of oligomenorrhea and ammenorrhea, but also to restore fertility and decrease risk factors for morbidity and mortality. This clinical example of PCOS gives a glimpse into the interrelatedness and complexity of women’s body systems and begins to allow us to shift focus from pelvis to person.

Hx:

YL is a 25-year-old woman who presented to my office for her “annual” physical exam. Her main health concern “was having a regular period.”

PMHx:

Oligomenorrhea and occasional ammonorrhea since menarche at age 12. Ammenorrhea responded to treatment with methoxyprogersterone acetate. At the time I first saw her she had been on oral contraceptives since age 19. Prior to seeing me she was referred to a gynecologist “to see if she had too many male hormones,” because she did not have regular menstrual cycles.

She was not in need of contraception at this time and desired to become pregnant at some future date. She was concerned about the use of BCP’s and wondered what her options were for future fertility.

PE:

HT 5’4", WT 184 lbs., BP118/76, P 80 Skin: hirsute, acne, acanthosis nigricans The rest of her physical exam was entirely normal including her pelvic exam

Studies:

blood glucose=86 (fasting <126), thyroid stimulating hormone=1.0 (0.8-5.0), cholesterol= 158 (<200), triglycerides=323 (<200), HDL=49 (>50), LDL=69 (<160)

Discussion

YL exhibits many of the classical features of a woman with polycystic ovarian syndrome (PCOS) including her history of irregular menses and ammenorrhea responding to progesterone withdrawal. Her physical exam is consistent with PCOS: including hirsutism and acne suggestive of increased androgen production, acanthosis nigricans associated with insulin resistance, and increased BMI also related to insulin resistance, and which may also be a function of other neuroendocrine abnormalities including interactions with leptin (known to be associated with eating disorders). Laboratory values such as elevated triglycerides are a common feature of PCOS.

Her history suggests she is at higher risk of long term sequelae of PCOS: reproductive, and non-reproductive. These sequlae include infertility, cardiovascular disease secondary to insulin resistance, and diabetes mellitus type II(adult onset) especially at the time of menopause. Although oligomenorrheic or ammenorrheic , these women are not at risk for osteoporosis, rather the increased estrogen and decreased progesterone puts women at risk for endometrial hyperplasia and endometrial cancer. Other potential sequelae are disorders of thyroid function. The aim of the diagnostic work-up is to identify risk factors, determine which patients will benefit from certain therapies, and monitor response to treatment. Studies should include FBS, insulin/glucose ratio, thyroid function studies, lipid profile, and may include LH, testosterone, and pelvic ultrasound. If classical signs and symptoms are not present, or there is concern for adrenal hyperplasia or cancer, other tests may include FSH, DHEA, DHEA-S, androstenedione, dihydrotestosterone, 17- OH progesterone, prolactin urinary 17- hydroxysteroids, and 17-ketosteroids, among others.

Therapeutic Options

Historically, therapeutic options consisted of wedge resection of the ovaries, which tended to temporarily restore menses, but other effects on the body were unknown. The thinking was that the endocrine abnormalities were a function of the enlarged ovaries and resultant excess production of androgens. Such surgery was not an option for the population of women without enlarged ovaries, and is not performed today.

Contemporary therapies consist of cycling women with progesterone or OCPs. This restores menses,however, does not address infertility. Infertility has been treated with ovulation-inducing agents such as clomiphene, which confers a risk of multiple gestation. Neither of these options addresses whole-body care for women.

The best approach to PCOS involves an acknowledgement of the complexity of the neuroendocrine and other systems, and their interrelatedness, and distancing ourselves from our linear “cause and effect” model. Hormonal effects are not compartmentalized to a single organ or organ system, but are rather wide and varied. Through the “complexity” lens, treating insulin resistance becomes a logical option.

More than a decade ago hyperinsulinism in PCOS was well documented in the endocrinology literature. Furthermore, insulin-like growth factors (IGF) were noted to cause the insulin resistance responsible for many of the clinical signs and symptoms of PCOS. In addition to insulin sensitivity in vasculature, adipose, and muscular tissue, the ovaries are sensitive to hyperinsulinism, producing elevated levels of androgens as a consequence. With this in mind, diet and exercise will likely benefit most women — even those with normal BMI’s, who may have abnormal insulin/glucose ratios. There is ample evidence that many women with documented abnormalities of insulin/glucose ratios benefit from therapy with agents such as metformin. This treatment, in decreasing insulin resistance, decreases the risk of cardiovascular sequelae and DM, and may restore regular menstrual cycles and fertility. Treatment for hyperlipidemia may also be in order to avoid the triad of Syndrome X.

The evolution of thinking about PCOS underscores the complexity of women’s health care and the interrelations among all systems. By splitting women’s reproductive systems from the rest of the body we have fragmented care for women, leading to delays in understanding and effective treatment of this very common problem.

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