Polycystic Ovary Syndrome

Polycystic Ovary Syndrome (PCOS) is primarily characterized by ovulatory dysfunction and hyperandrogenism. Adolescent girls with PCOS have increased risk of infertility, metabolic syndrome, type 2 diabetes, and cardiovascular disease. A diagnosis of PCOS should be considered for any adolescent with hirsutism, acanthosis nigricans, persistent acne, menstrual irregularity, or obesity. PCOS is a syndrome with multiple clinical presentations, therefore any of the above clinical signs should cause concern for PCOS.

Diagnosis

Three sets of diagnostic criteria exist for PCOS (NIH, Rotterdam, and AES). The NIH criteria are the most widely accepted and recommended in diagnosing adolescents. They include the following:

1. Hyperandrogenism (preferably supported with biochemical testing of free Testosterone and/or DHEAS, although clinical symptoms of hirsutism or acne are sufficient)

AND

2. Abnormal menstrual pattern (primary amenorrhea, oligomenorrhea, or dysfunctional uterine bleeding)

Differential Diagnosis

1. Congenital Adrenal Hyperplasia

2. Ovarian Steroidogenic Block

3. Cushing Syndrome/Cortisol Resistance

4. Hyperprolactinemia

5. Acromegaly

6. Insulin Resistance Disorders

7. Virilizing Tumors

8. Thyroid Dysfunction

9. Drugs (Anabolic Steroids, Valproic Acid)

Genetics

Nearly 1/3 of sisters of PCOS patients have elevated testosterone levels and ½ of those patients will later develop symptoms meeting PCOS diagnosis by NIH criteria. Over 1/3 of PCOS patients also had a parent with metabolic syndrome or diabetes mellitus. No specific genes have been identified that cause PCOS. Proposed genes likely regulate the hypothalamic-pituitary-ovarian axis. Due to this high frequency of PCOS and metabolic syndrome in family members it is recommended that family be screened for PCOS and metabolic syndrome, especially those who are obese.

Treatment

Treatment of adolescent PCOS is mainly directed towards correcting menstrual irregularity, hirsutism, acne, obesity, and insulin resistance.

It is important to treat menstrual irregularity as chronic anovulation increases the risk of endometrial hyperplasia and endometrial carcinoma. Anemia can also be a result of dysfunctional uterine bleeding. First line treatment is generally combination OCP. Progestins inhibit the endometrial proliferation while Estrogen reduces the activity of the hypothalamic-pituitary-gonadal axis, which reduces androgen production. This aids in controlling the skin problems of hirsutism and acne.

Several options of OCP are available including, but not limited to, Drospirenone, Norgestimate, or Ethynodiol diacetate. Treatment should begin quickly after diagnosis and then assessed by evaluating clinical symptoms and androgen levels after 3 months. If successful, OCP treatment should then continue for five years past menarche or until the patient has lost substantial weight. Then treatment can be withheld for a few months to allow recovery of normal hypothalamic-pituitary-gonadal axis. This will allow the physician to observe if the menstrual abnormality still persists. If OCP treatment is not successful or patient is unwilling to take OCPs other options include progestin alone, low dose glucocorticoid therapy, and GnRH agonist therapy.

Hirsutism should initially be treated with cosmetic measures such as shaving, hydrochloride cream, or laser therapy. Endocrinologic treatment of hirsutism is off label but may be used if cosmetic measures are inadequate.

Weight loss is highly recommended as it improves ovulation, acanthosis nigricans, and hyperandrogenism in obese patients. Metformin and Thiazolidinediones may also be added to further reduce insulin resistance, promote ovulation, and lower androgen levels.

Definitions

Hirsutism- excessive sexual hair that appears in a male pattern.

Primary Amenorrhea- lack of menarche by 15 years of age or more than three years after the onset of breast development.

Oligomenorrhea- missing more than four period per year (>45 days between menstrual periods) or >90 days without another period after menarche.

Dysfunctional Uterine Bleeding- bleeding intervals of less than 21 days, bleeding lasting greater than 7 days, or bleeding that requires pad or tampon changes more than every one or two hours.

References

1. American Academy of Pediatrics Committee on Adolescence, American College of Obstetricians and Gynecologists Committee on Adolescent Health Care, Diaz, A et al. Menstruation in girls and adolescents: using the menstrual cycle as a vital sign. Pediatrics 2006; 118:2245.

2. Buggs C, Rosenfeild RL. Polycystic ovary syndrome in adolescence. Endrocinol Metab Clin North Am 2005; 34:677.

3. Ehrmann DA. Polycystic ovary syndrome. N Engl J Med 2005; 352:1223.

4. Woods KS, Reyna R, Azziz R. Effect of oral micronized progesterone on androgen levels in women with polycystic ovary syndrome. Fertil Steril 2002; 77:1125

5. Zawadzki J, Dunaif A. Diagnostic criteria for polycystic ovary syndrome: Towards a rational approach. In: Polycystic Ovary Syndrome, Dunaif A, Givens J, Haseltine F, Merriam G, Blackwell Scientific Publications, Cambridge 1992. P.377