Polycystic Ovary Syndrome in Adolescents

Polycystic Ovary Syndrome in Adolescents

Polycystic ovary syndrome (PCOS) is a very common endocrine disorder that is present in approximately 7% of reproductive age women ^[1]. It is a heterogeneous syndrome that usually present during adolescence and is characterized by features of anovulation (amenorrhea, oligomenorrhea and irregular menstrual cycle) combined with symptoms of androgen excess (hirutism, acne, alopecia) ^[2]. In the United States, PCOS is the single most common endocrine cause of annovulatory infertility and type 2 diabetes ^{[3, 4]}.

Polycystic ovary syndrome occurs in both normal -weight and overweight women, and obesity is a frequent comorbidity which often precedes the development of PCOS ^[5]. The prevalence of impaired glucose tolerance [IGT] in obese young women with PCOS has been estimated to be as high 30% to 40%, with an additional 5% to 10% having diabetes ^{[6, 7]}.

Etiopathogenic considerations

PCOS is a complex interaction between genetic and environmental factors. Accepted etiologic theories include disordered neuroendocrine gonadotropin secretion, hyperandrogenism, insulin resistance and hyperinsulinemia or a combination thereof ^[8]. In many ovarian hyperandrogenism appears to be the primary dysfunction with additional related finding of hyperinsulinism, insulin resistance, elevated luteinizing hormone (LH) and associated of obesity as well. However, it is recognized that there is heterogeneity in this syndrome ^[9].  

Causes of Polycystic Ovary Syndrome

There have not the exact cause of PCOS. However, several factors may play a role in whether or not develop PCOS. These include:

·         Heredity: If one have family members with PCOS or a history of diabetes then she is more likely to develop PCOS.

·         Higher level of insulin: When insulin level is too much means greater than normal insulin range then cell become resistant to it. This can cause increased androgen production and difficulty ovulating.

·         Higher level of androgen: When ovaries produce too much androgen, which may develop hirsutism and acne.

·         Inflammation: women with PCOS have a type of low-grade inflammation that stimulate ovaries to produce androgen.

Sign and Symptoms of Polycystic Ovary Syndrome

·        Irregular menstrual cycle, which means having period more than once a month or every few months, or never having period.

·        Periods that is very heavy or very light.

·        Unwanted hair growth on face, chest, upper arms, legs and nipples.

·        Thinner hair on head.

·        Weight problems.

Teenagers with PCOS also are at higher risk for type 2 diabetes, high blood pressure and high cholesterol.

Diagnosing PCOS in Adolescents

Controversy exists regarding diagnosing PCOS in adolescents where normal pubertal circumstance can overlap with the PCOS phenotype.

Three guidelines exist for PCOS in adult women; each using a combination of the following diagnostic criteria:

·         Androgen excess

·         Ovulatory dysfunction

·         Polycystic ovarian morphology (PCOM)

1.      Androgen Excess:

a)      Moderate to severe hirsutism and persistent acne unresponsive to topical therapy and clinical evidence of potential androgen excess in the adolescent.

b)      Biochemical androgen excess is the best proved by persistent elevation of serum total or free testosterone level.

2.      Ovulatory Dysfunction: Recommended evidence of ovulatory dysfunction includes:

a)      Consecutive menstrual intervals >90 days even in the first year after menstrual onset;

b)      Menstrual intervals persistently <21 days or >45 days two or more years after menarche; and

c)      Lack of menses by 15 years or 2-3 years after breast budding.

Providing a diagnostic label of PCOS is not necessary to effectively manage adolescent girls with PCOS features.

PCOS Treatment Options

The most commonly treatment options include oral contraceptive pills (OCPs) and metformin. For acne associated with PCOS, a variety of treatment options exist such as topical and oral medications.

Oral Contraceptive Pills (OCPs)

·         Interfere with Hypothalamic- Pituitary-Ovarian axis, suppressing endogenous ovarian function and thus also decreeing androgen secretion by the ovary.

·         Increase Sex Hormone Binding Globulin (SHBG), that binds up and decreases free testosterone levels. These effects all help decrease the hyperandrogenemia.

Metformin

It is generally accepted to be an insulin sensitizer, allowing the body to utilize insulin more effectively and thus treat the insulin resistance believed to contribute to PCOS signs and symptoms.

Side effects:  Gastrointestinal side effects are very common, and patients must be counseled on how to best avoid and manage the side effects. This involves proper dosing protocols.

Spironolactone

·         It is a competitive androgen receptor antagonist with diuretic effects ( potassium-sparing).

·         It is typically used as an adjunct to OCPs in helping ease the hyperandrogen symptoms.

Side effects: It disturbs the electrolyte disturbances (such as hyperkalemia).

Lifestyle changes:

Lifestyle changes through healthy diet and exercise can help treat PCOS. As little as 5% weight losses can help improve cardiovascular health and improve insulin use.

Long Term Consideration for Patients

For women with PCOS, consideration should be given to contraception, fertility, risk for endometrial hyperplasia and endometrial and cancer, and potential endocrine-related conditions.

Contraception

·         Ovulation react will likely improve with PCOS treatment, thus an assessment of contraceptive needs in paramount.

·         Women with PCOS who are sexually active and do not desire pregnancy should be use a form of contraception.

Fertility

·         Managing insulin levels and obtaining a healthy weight is helpful to increase the chance of successful ovulation. In some case medications may be used to induce ovulation.

·         While some women with PCOS have difficulty conceiving, some women have no difficulty at all.

·         Following an gynecologist is necessary.

·         Preconception counseling should focus on obtaining a healthy weight, regular exercise, and tobacco/ alcohol/ drug cessation.

Malignancy

·         The risk of endometrial hyperplasia is increased in women who do not regularly ovulate.

·         PCOS treatment is multidimensional and should have a component focused on reducing the risk of endometrial hyperplasia and malignancy.

·         Abnormal uterine bleeding should be evaluated.

Summary and Conclusions

Depends on current diagnostic recommendations, the patient in the case presentation vignette meets the diagnostic criteria for PCOS in adolescent. She has proved of ovulatory dysfunction and both clinical and laboratory evidence of hyperandrogenism. In addition, her hemoglobin A1C indicates pre-diabetes. She requires further evaluation for metabolic and psychologic comorbidity. Lifestyle counseling with combined initiation of COC and metformin would be an appropriate first step in the ongoing care of the patient. 

REFERENCES

1.      American college of Obstetricians and Gynecologists. ACOG practice Bulletin No. 108: polycystic ovary syndrome. Obstet Gynecol 2009; 114: 936-49

2.      Zawadski JK, Dunaif A, Givens JR, Haseltine F, editors. Polycystic ovary syndrome. Boston: Blackwell Scientific; 1992:337-84.

3.      Franks S. polycystic ovary syndrome in adolescent. Int  j Obes 2008;32:1035-41.

4.      Ehrmann DA, Kasza K, Azziz R, Legro RS, Ghazzi MN, Group PCTS. Effects of race and family history of type 2 diabetes on metabolic status of women with polycystic ovary syndrome. J Clin Endocrinol Metab 2005; 90:66-71.

5.      Motta AB. The role of obesity in the development of polycystic ovary syndrome. Curr pharm Des 2012; 18:2482-91.

6.      Legro RS. Diabetes replaces and risk factors in polycystic ovary syndrome. Obstet Gynecol Clin North Am 2001; 28; 99-109.

7.      Ehrmann DA, Barnes RB, Rosenfield RL, Cavaghan MK, Imperial J. prevalence of impared glucose tolerance and diabetes in woman with polycystic ovary syndrome. Diab care 1999; 22:141-6.

8.      Dumesic DA, Oberfield SE, Stener Victorin E, et al. Scientific Statement on the diagnostic Criteria, Epidemiology, Pathophysiology, and molecular Genetics of Polycystic Ovary Syndrome. Endor Rev 2015; 36: 487-525. 10.1210/er.2015-2018.

9.      Rosenfield RL, Ehrmann DA. The pathogenesis of polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited. Endcor Rev 2016; 37: 467-520.10.1210/er.2015-1104.