Virilization

A member on Docplexus had a query on hirsuitism.

I have uploaded simple under graduate level lecture on Hirsuitism and Cong Adr Hyperplasia, which should give a simple and lucid overview of the distressing condition.

Several treatment options are available. Never forget to tell the patient that benefits will begin in 3 months time or so, otherwise they will run from clinic to clinic without relief.

1. Virilization

2. Virilization Clinical features associated with a high level of male hormones in women. Hirsuitism Acne Deepening of voice Increased muscle mass Breast atrophy

3. Hirsutism Excessive growth of thick terminal hair in a male distribution in women (upper lip, chin, chest, back, lower abdomen, thigh, forearm) Most common presentation of endocrine disease. DD: Hypertrichosis , which is generalised excessive growth of vellus hair . The aetiology is androgen excess

4. Androgens and Hirsuitism Hirsutism can be caused by either an increased level of androgens or an oversensitivity of hair follicles to androgens. Testosterone stimulates hair growth, (size, intensity of growth and pigmentation).

5. obesity/insulin and Hirsuitism High circulating levels of insulin are implicated in women for the development of hirsutism . Obese (insulin resistant hyperinsulinemic ) women are at high risk of becoming hirsute. Treatments that lower insulin levels lead to a reduction in hirsutism . High concentration of insulin (directly and through IGF I) is thought to stimulate theca cells in ovaries to produce androgens.

6. Hirsuitism : Causes Idiopathic Polycystic ovarian syndrome Congenital adrenal hyperplasia Exogenous androgen administration Androgen-secreting tumour of ovary or adrenal cortex

7. Hirsuitism : Idiopathic Often familial Mediterranean or Asian background Investigations: normal Treatment: Cosmetic measures Anti-androgens

8. Hirsuitism : PCOS Aetiology -poorly understood Constellation of clinical and biochemical features of varying severity Obesity Oligomenorrhoea / Secondary amenorrhoea Infertility multiple cysts in the ovaries

9. Hirsuitism : PCOS Mechanisms* Manifestations Pituitary dysfunction High serum LH High serum prolactin Anovulatory menstrual cycles Oligomenorrhoea Secondary amenorrhoea Cystic ovaries Infertility Androgen excess Hirsutism Acne Obesity Hyperglycaemia Elevated oestrogens Insulin resistance Dyslipidaemia Hypertension

10. Hirsuitism : PCOS Investigations: LH:FSH ratio > 2.5:1 Minor elevation of androgens Mild hyperprolactinaemia Treatment Weight loss Cosmetic measures Anti-androgens Insulin-sensitising drugs

11. Hirsuitism : Congenital adrenal hyperplasia 95% 21-hydroxylase deficiency Clinical Features: Pigmentation History of salt-wasting in childhood Ambiguous genitalia Adrenal crisis when stressed

12. Hirsuitism : Congenital adrenal hyperplasia Investigations Elevated androgens, suppressible with dexamethasone Abnormal rise in 17OH-progesterone with ACTH Treatment Glucocorticoid replacement administered in reverse rhythm to suppress early morning ACTH

13. Hirsuitism : Exogenous androgens Athletes Virilised Investigations: Low LH and FSH Analysis of urinary androgens may detect drug of misuse Treatment: Stop steroid misuse

14. Hirsuitism : Androgen-secreting tumour ovary or adrenal cortex Rapid onset virilisation : clitoromegaly deep voice balding breast atrophy

15. Hirsuitism : Androgen-secreting tumour ovary or adrenal cortex Investigations: High androgens which do not suppress with dexamethasone or oestrogen Low LH and FSH CT or MRI usually demonstrates a tumour Treatment: Surgical excision

16. Hirsuitism : Clinical approach The severity of hirsutism is subjective Important observations are – Drug and menstrual history Calculation of BMI Measurement of BP Examination for virilisation ( clitoromegaly , deep voice, male-pattern balding, breast atrophy) Acne vulgaris Cushing's syndrome When recent & with virilisation, suggestive of a rare androgen-secreting tumour

17. Hirsuitism : Investigations Random blood sampling for testosterone, prolactin , LH and FSH

18. Hirsuitism : Investigations Random blood – testosterone, Prl , LH and FSH. If Cushingoid features +: Overnight 1 mg Dexa suppression test

19. Hirsuitism : Investigations Random blood – testosterone, Prl , LH and FSH. If Cushingoid : Overnight 1 mg DST If testosterone levels are high (with low LH & FSH): look for source of excess androgen

20. Hirsuitism : Investigations Random blood – testosterone, Prl , LH and FSH. If Cushingoid : Overnight 1 mg DST If testosterone high (with low LH & FSH): ? source Suspected CAH (21-hydroxylase deficiency): short ACTH stimulation test, with measurement of 17OH-progesterone

21. Hirsuitism : Investigations Androgen-secreting tumours: Testosterone is not suppressible by Dexamethasone Overnight or 48-hour low-dose suppression test Oestrogen (30 μg / day X 7 days) CT or MRI of the adrenals and ovaries

22. Hirsuitism : Treatment Cosmetic measures - shaving, bleaching and waxing Electrolysis and laser treatment : for small areas Eflornithine cream : Inhibits ornithine decarboxylase in hair follicles & may reduce hair growth

23. Hirsuitism : Treatment Weight reduction for obese patients with PCOS enhances insulin sensitivity reduces the peripheral conversion of androgens by adipose tissue reduces metabolic clearance of cortisol , thereby reducing ACTH-dependent adrenal androgen secretion

24. Hirsuitism : Treatment If these conservative measures have failed- Anti-androgen therapy The life cycle of hair follicles is at least 3 months, so no improvement is likely before this. Only replacement hair growth is suppressed. Insulin-sensitising drugs ( thiazolidinediones and biguanides ) Have a role but unless the patient has lost weight, the hirsutism will return once discontinued.

25. ANTI-ANDROGEN THERAPY Androgen receptor antagonists Cyproterone acetate Spironolactone 5 α- reductase inhibitors (prevents conversion of testosterone to active form)- Finasteride Suppress ovarian steroid production and elevate SHBG (sex hormone-binding globulin ) Oestrogen (+ Cyproterone acetate) Suppress adrenal androgen production - Glucocorticoids