Overview

Definition:
-Hyperandrogenism in adolescent girls refers to a state of excessive androgen production or activity, leading to clinical signs and symptoms of masculinization
-Polycystic Ovary Syndrome (PCOS) is the most common cause of hyperandrogenism in this age group, characterized by a combination of ovulatory dysfunction, hyperandrogenism, and polycystic ovarian morphology on ultrasound (though the latter is not essential for diagnosis in adolescents).
Epidemiology:
-PCOS is estimated to affect 15-20% of reproductive-aged women, with onset often in adolescence
-Studies suggest prevalence rates of 6-23% in adolescent girls, varying by diagnostic criteria used
-It is a leading cause of menstrual irregularities and hyperandrogenic symptoms in this demographic.
Clinical Significance:
-Undiagnosed or inadequately managed hyperandrogenism and PCOS in adolescents can lead to significant physical and psychological distress
-Long-term consequences include metabolic syndrome, type 2 diabetes mellitus, cardiovascular disease, infertility, and impaired quality of life
-Early and accurate evaluation is crucial for timely intervention and prevention of these sequelae.

Clinical Presentation

Symptoms:
-Irregular menstrual cycles (oligomenorrhea, amenorrhea) usually starting within 1-2 years of menarche
-Hirsutism, characterized by excessive hair growth in a male-like pattern (e.g., face, chest, abdomen)
-Acne vulgaris, often severe or persistent beyond typical adolescent acne
-Androgenic alopecia (hair thinning on the scalp)
-Weight gain or obesity, particularly central obesity
-Acanthosis nigricans, indicative of insulin resistance
-Mood disturbances, anxiety, and depression.
Signs:
-Evidence of hirsutism on physical examination, often graded using the Ferriman-Gallwey score
-Moderate to severe acne vulgaris
-Evidence of alopecia
-Clinical signs of obesity or excess central adiposity
-Acanthosis nigricans on neck, axillae, or other friction areas
-Clitoromegaly (rare, suggestive of more severe hyperandrogenism or an androgen-secreting tumor).
Diagnostic Criteria:
-The Rotterdam criteria are commonly used, requiring at least two of the following three features for diagnosis: 1
-Oligo- and/or anovulation
-2
-Clinical and/or biochemical evidence of hyperandrogenism
-3
-Polycystic ovaries on transvaginal ultrasound (at least 12 follicles measuring 2-9 mm in diameter in each ovary and/or ovarian volume > 10 mL)
-In adolescents, diagnosis requires the exclusion of other androgen excess disorders, and ultrasound findings may be less specific due to normal physiological changes
-The presence of oligo-anovulation and hyperandrogenism, with exclusion of other etiologies, is often sufficient for diagnosis in this age group.

Diagnostic Approach

History Taking:
-Detailed menstrual history, including age of menarche, cycle regularity, duration, and flow
-Onset and progression of hyperandrogenic symptoms (hirsutism, acne, hair loss)
-History of obesity or rapid weight gain
-Family history of PCOS, diabetes, or cardiovascular disease
-Medications that can cause hyperandrogenic symptoms (e.g., certain anticonvulsants, anabolic steroids)
-Symptoms suggestive of adrenal or pituitary disorders (e.g., rapid virilization, galactorrhea, headaches).
Physical Examination:
-Assess Tanner stage for pubertal development
-Measure height, weight, and calculate BMI
-Perform Ferriman-Gallwey scoring for hirsutism
-Examine for acne and alopecia
-Inspect for acanthosis nigricans
-Palpate thyroid
-Measure waist circumference and calculate waist-to-hip ratio
-Perform a pelvic examination (if clinically indicated and appropriate for age, to assess for clitoromegaly or other anomalies).
Investigations:
-Baseline laboratory tests: Follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, prolactin, thyroid-stimulating hormone (TSH)
-Total and free testosterone levels
-Dehydroepiandrosterone sulfate (DHEAS) and androstenedione (if DHEAS is elevated or clinical suspicion is high)
-17-hydroxyprogesterone (17-OHP) to rule out non-classical congenital adrenal hyperplasia (NCCAH)
-HbA1c and fasting glucose/insulin to assess for insulin resistance and diabetes risk
-Lipid profile
-Pelvic ultrasound: May show polycystic ovaries but is not essential if other criteria are met and should be interpreted cautiously in adolescents
-Consider adrenal CT or MRI if marked hyperandrogenism, virilization, or elevated DHEAS suggests an adrenal tumor
-Consider pituitary MRI if hyperprolactinemia or other pituitary signs are present.
Differential Diagnosis:
-Congenital adrenal hyperplasia (CAH), particularly non-classical forms
-Cushing's syndrome
-Androgen-secreting tumors (ovarian or adrenal)
-Hyperprolactinemia
-Hypothyroidism
-Medications
-Idiopathic hirsutism
-Polycystic ovarian morphology on ultrasound alone without other features.

Management

Initial Management:
-Lifestyle modification is the cornerstone of management: dietary changes (balanced diet, reduced intake of refined carbohydrates and saturated fats) and regular physical activity
-Weight loss in overweight or obese individuals is paramount for improving hormonal balance and insulin sensitivity
-Patient education and counseling regarding the chronic nature of PCOS and its management are essential.
Medical Management:
-Combined oral contraceptive pills (COCPs) are first-line therapy for menstrual regulation and androgen suppression
-Examples include ethinyl estradiol/drospirenone or ethinyl estradiol/cyproterone acetate
-Anti-androgen medications (e.g., spironolactone, finasteride) may be added for resistant hirsutism, but caution is advised in adolescent girls of reproductive potential due to teratogenicity
-use requires reliable contraception
-Metformin is indicated for patients with insulin resistance, impaired glucose tolerance, or type 2 diabetes, and may help improve menstrual regularity and androgen levels
-Other medications like eflornithine cream can be used topically for hirsutism.
Surgical Management:
-Surgical intervention is rarely indicated for PCOS in adolescents
-Ovarian drilling may be considered in select cases of severe anovulation resistant to medical management, but its long-term efficacy and safety in adolescents are still debated
-Surgical removal of androgen-secreting tumors is indicated if malignancy is suspected or confirmed.
Supportive Care:
-Psychological support is crucial due to the impact of PCOS on self-esteem and body image
-Referrals to dietitians for nutritional counseling
-Regular monitoring of weight, BMI, blood pressure, and glucose levels
-Dermatological evaluation for severe acne or alopecia
-Counseling on reproductive health and fertility planning as the patient approaches reproductive age.

Complications

Early Complications:
-Psychological distress, anxiety, and depression due to cosmetic concerns
-Worsening acne and hirsutism
-Metabolic disturbances like insulin resistance and dyslipidemia.
Late Complications:
-Infertility
-Gestational diabetes and preeclampsia in pregnancy
-Increased risk of type 2 diabetes mellitus
-Cardiovascular disease (hypertension, coronary artery disease)
-Endometrial hyperplasia and increased risk of endometrial cancer (if amenorrhea is prolonged without progestin withdrawal)
-Sleep apnea
-Non-alcoholic fatty liver disease.
Prevention Strategies:
-Early diagnosis and consistent management of hyperandrogenism and metabolic abnormalities
-Emphasis on sustainable lifestyle modifications (diet and exercise)
-Regular medical follow-up to monitor for complications and adherence to treatment
-Patient education on long-term health risks and self-management strategies.

Prognosis

Factors Affecting Prognosis:
-Early diagnosis and initiation of appropriate treatment
-Severity of hyperandrogenism and metabolic abnormalities at presentation
-Patient adherence to lifestyle modifications and medical therapy
-Genetic predisposition
-Presence of obesity and insulin resistance.
Outcomes:
-With consistent management, many adolescents can achieve regular menstrual cycles, reduce hyperandrogenic symptoms, and improve metabolic parameters
-However, PCOS is a chronic condition, and long-term monitoring is necessary
-Fertility may be affected, but many can achieve pregnancy with appropriate treatment
-The risk of long-term metabolic and cardiovascular complications can be significantly reduced with proactive management.
Follow Up:
-Regular follow-up every 6-12 months is recommended, or more frequently if symptoms are severe or changing
-This includes reassessment of menstrual regularity, hyperandrogenic symptoms, weight, BMI, blood pressure, and metabolic parameters (glucose, lipids)
-Transition of care to an adult endocrinologist or gynecologist as the patient approaches adulthood is essential
-Counseling on family planning and pregnancy risks should be ongoing.

Key Points

Exam Focus:
-Remember the Rotterdam criteria and the importance of excluding other causes of hyperandrogenism
-First-line management involves lifestyle changes and COCPs
-Metformin is used for insulin resistance
-DHEAS is a key marker for adrenal androgen excess
-Ultrasound is less critical in adolescents compared to adults for PCOS diagnosis.
Clinical Pearls:
-Always consider NCCAH in adolescent girls with hyperandrogenism, especially if there is a family history or rapid virilization
-Acanthosis nigricans is a strong indicator of insulin resistance
-Don't underestimate the psychological impact of PCOS on adolescents
-provide holistic care
-Transition of care planning should begin early.
Common Mistakes:
-Diagnosing PCOS based solely on ultrasound findings in adolescents without fulfilling other criteria
-Inadequate exclusion of other endocrine disorders
-Over-reliance on pharmacologic therapy without emphasizing lifestyle modifications
-Inconsistent follow-up and monitoring for long-term complications.