Hyperandrogenism Dr Jack Biko MB. BCh (Wits), MMED O & G (Pret), FCOG (SA), Dip Advanced Endoscopic Surgery(Kiel, Germany) 2012
Hyperandrogenism Excessive production of androgens Adrenal glands main source of androgens Ovaries also produce androgens Men manifest few symptoms Occur in postmenopausal women as well
Hyperandrogenism Androgens are a byproduct of cortisol synthesis ACTH a major determinant of androgen production
Cortisol production
Adrenal androgens Dehydroepiandrosterone (DHEA) Dehydroepiandrosterone sulphate (DHEAS) 90% produced by adrenal glands 10% by ovaries / Testis
Hyperandrogenism DHEA and DHEAS do not have androgenic activity Converted to Testosterone in adrenal gland and peripheral tissue: Hair follicles, Sebaceous glands, External genitalia, Adipose tissue
Clinical features General appearance Mascular male body habitus Android obesity Skin changes Hirsutism (face, chin, chest, perineum) Alopecia Oily skin Acne vulgaris Male sweat changes Acanthosis nigrans
Clinical features Menstrual irregularities Amenorrhea Infertility Endocrine changes Hypertension Hyperlipidemia Impaired glucose tolerance
Clinical features Deepening of voice Clitoromegally Increased libido Associated conditions Hashimoto s thyroiditis Graves disease
Clinical features Skin changes Hirsutism Alopecia Acanthosis nigrans Oily skin Acne vulgaris Male sweat changes Hyperandrogenic syndromes PCOS HAIR-AN syndrome
Clinical features Pubertal boys Increased rate of progression of puberty Rapid skeletal maturation Premature epiphyseal fusion Pubertal girls Virilization Amenorrhea Rapid skeletal maturation Premature epiphyseal fusion
Clinical features Adult male Minimal clinical changes Inhibition of GNRH secretion testis atrophy leading to: (1) low testosterone levels and (2) low sperm count Infertility!! Adult females Hirsutism Acne Male pattern baldness Menstrual problems Ovulatory dysfunction infertility
Causes of hyperandrogenism Medications: Anabolic steroids Danazol Metoclopramide Phenothiazines COC s (ovral, nordette, triphasil Resepine Endogenous overproduction: CAH: 21 and 11 hydroxylase deficiency Cushing s syndrome Ovarian cause: PCOS, Hyperthecosis, HAIR AN syndrome
Non-tumour related causes Adrenal causes CAH 21 hydroxylase deficiency 11 hydroxylase deficiency. Cushing syndrome Ovarian causes PCOS Hyperthecosis HAIR-AN syndrome
Tumour related causes Adrenal tumours Adrenocortical tumour Adrenal adenoma Adrenal carcinoma Ovarian tumours Arrhenoblastoma Hilar cell ovarian tumour Krukenberg tumour
Congenital adrenal hyperplasia Several autosomal recessive disorders Defect in cortisol synthesis Defect in aldosterone synthesis Accumulation of precursors
HAIR-AN syndrome Hyperandrogenism Insulin resistance Acanthosis nigrans
Gestational hyperandrogenism Changes in pregnancy: hirsutism, acne, temporal balding, clitoromegally, deepening voice. Palpable solid or cystic mass may be present Luteoma, Theca lutean cysts, Ovarian tumour, Adrenal tumour, Placental aromatase deficiency, Exogenous androgens/ progestogens
Ambiguous genitalia
Ambiguous genitalia
Investigations Pelvic ultrasound FSH, LH, Oestradiol, DHEA, DHEAS, Testosterone, SHBG,FBC, TSH, Prolactin UKE, Fasting glucose and insulin CT scan MRI
Management Lifestyle changes Metformin (reduction in testosterone) COC Anti-androgens (aldactone, proscar) Refer to endocrine / gynaecologist Follow up patient
Management Reduce androgens Manage the cosmetic effects Manage infertility Treatment is life long
Management COC s: must contain 30 35ug E3 and less androgenic progestin Inhibit LH, stimulate SHBG production 60 100% improvement in hirsutism Must use for at-least 6months before improvement can be noted Hirsutism recurs if Rx stopped
Management Anti-androgens: not recommended as first line or as monotherapy. Use as add-on to COC Spironolactone, Finesteride, Cyprosterone acetate, Flutamide(hepatotoxic) Metformin: no effect on hirsutism
Management Cosmetic therapy: Shaving, Plucking, Waxing Fertility: ovulation induction with clomid
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