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Hirsutism 2021

  1. 1. Evaluation & Treatment of Hirsutism An Endocrine Society Guideline, 2018 Canadian Society Of Obs Gyn, 2017 Prof. Aboubakr Elnashar Benha university Hospital ABOUBBAKR ELNASHAR CONTENTS 1. INTRODUCTION 2. DEFINITIONS 3. PATHOGENESIS 4. CAUSES 5. CLINICAL EVALUATION 6. INVESTIGATIONS 7. TREATMENT ABOUBBAKR ELNASHAR
  2. 2. ▪ Gynecological, Endocrinological, Cosmetic & Psychogenic: {great anxiety, nature of the disease, social acceptance} ▪ Incidence ▪ Not known ▪ Mediterranean> Asian ▪ American females: 10% ▪ European: 5% ABOUBBAKR ELNASHAR ▪ Types of hair Lanugo Fetal hair Vellus ▪ Short, ▪ fine, ▪ Unpigmented ▪ Before puberty Terminal ▪ Long, ▪ coarse, ▪ pigmented ▪ arises from vellus hair ▪ Clinically, terminal hairs can be DD from vellus hairs by: ▪ their length (i.e.`0.5 cm) ▪ usually pigmented. ABOUBBAKR ELNASHAR
  3. 3. Non sexual Ambi-sexual Male sexual Sites ▪ Lower parts of the scalp ▪ eye brow ▪ Lashes ▪ fore-arms, ▪ lower legs ▪ Temporal & vertical parts of the scalp ▪ Axilla ▪ Lower pubic hair. ▪ Ears ▪ Nasal tip ▪ Chin ▪ Sternum ▪ Upper pubic triangle ▪ Back . Depend on Growth hormone from pituitary Androgen in low concentration from the adrenals & ovaries in females & adrenals in male Androgen in high concentration ▪ Sites of hair ABOUBBAKR ELNASHAR ▪ Sources of androgens ABOUBBAKR ELNASHAR
  4. 4. ▪ Androgen in the blood Male Normal female Hirsute female Free 3% 1% 2% Albumin 19% 19% 19% SHBG 78% 80% 79% ABOUBBAKR ELNASHAR ▪ Androgen at target cell (hair follicle) Testosterone (T) 5œ-reductase. Dihydrtestosterone (DHT) Androstanediol Glucuronide 3 alpha androstanediol glucuronide(3 alpha AG) ABOUBBAKR ELNASHAR
  5. 5. 2. DEFINITIONS ▪ Hirsutism: Excessive terminal hair in male sexual sites (excessive hair in androgen-dependent areas; i.e., sexual hair) in women. ▪ Local hair growth: Unwanted localized hair growth in the absence of an abnormal hirsutism score. ▪ Patient-important hirsutism: Unwanted sexual hair growth of any degree that causes distress for women to seek additional treatment. ▪ Idiopathic hirsutism: Hirsutism without hyperandrogenemia or other signs or symptoms indicative of a hyperandrogenic endocrine disorder. ABOUBBAKR ELNASHAR ❑Hypertrichosis ▪ Excessive growth of (Lanugo, vellus or terminal) hair in ▪ Non-sexual sites (James et al, 2005) ▪ Cong ▪ Acquired ▪ Localized ▪ Generalized Congenital hypertrichosis lanuginosa Drug-induced hypertrichosis ABOUBBAKR ELNASHAR
  6. 6. 3. PATHOGENESIS ▪ Hirsutism ▪ An increase in 4 1. Androgen production 2. Sensitivity of the androgen receptors at the level of the hair follicle. 3. Activity of 5œ-reductase. 4. Transformation of the vellus to terminal hair. {Androgens will convert lanugo & vellus hair to terminal hair}. ▪ Not an increase in Number of hair follicles but an alteration in their character. ABOUBBAKR ELNASHAR 4. Etiology Hirsutism can be classified into 1 of 3 groups based on etiology: (CSOG, 2017) 1. Hyperandrogenic hirsutism (including PCOS or androgen-secreting tumours) 2. Non-androgenic hirsutism (including medication- induced hirsutism) 3. Idiopathic hirsutism (II-3). The majority of hirsutism is due to androgen excess (≥80%), and the majority of women with hirsutism (70% to 80%) have PCOS ABOUBBAKR ELNASHAR
  7. 7. ABOUBBAKR ELNASHAR I. Hyperandrogenic ▪ PCOS ▪ The most common cause of hirsutism ▪ Although adolescents may present with hirsutism, the diagnosis of PCOS in these young women is controversial given that the diagnostic features of PCOS may be normal pubertal physiologic events ▪ Roterdam criteria: combination of 2 of 3: ▪ unexplained chronic hyperandrogenism ▪ Oligoovulation ▪ US of PCO ABOUBBAKR ELNASHAR
  8. 8. ABOUBBAKR ELNASHAR ▪ PCOS ▪ frequently associated with metabolic syndrome that results from insulin resistance and/or central obesity and that requires considerations distinct from those for hirsutism itself. ▪ Obesity may worsen or cause features of PCOS ▪ Insulin resistance and hyperinsulinemia: hyperandrogenism in women with PCOS (II). ABOUBBAKR ELNASHAR
  9. 9. Examples of hirsutism affecting the back, chest, and abdomen PCOS with hirsutism (Ferriman and Gallwey score 4) on the abdomen ABOUBBAKR ELNASHAR ▪ Non-classical congenital adrenal hyperplasia (NCCAH) ▪ Often presents with hirsutism and has a clinical picture similar to that of PCOS. ▪ Prevalence: very low outside of specific high-risk ethnic groups (II-2) ▪ Present in 4.2% of hyperandrogenic women worldwide, although specific ethnic groups are at lower or higher risk ABOUBBAKR ELNASHAR
  10. 10. ❑Late onset congenital adrenal hyperplasia HLA Manifestations Incidence Subtype BW 14 Amenorrhea, Hirsutism +++ Late-onset BW 51 Virilization ++ Simple virilizing BW 47 Virilization, Salt loss + Salt-loosing ABOUBBAKR ELNASHAR ▪ Androgen-secreting tumors ▪ 0.2% of hyperandrogenic women; over half are malignant ABOUBBAKR ELNASHAR
  11. 11. II. Non hyperandrogenic: ▪ Drugs: ▪ Topical androgen use by a partner, ▪ Exogenous androgens or ▪ Anabolic steroids, or ▪ Valproic acid ▪ Cushing syndrome, acromegaly, hypothyroidism, and (rarely) hyperprolactinemia in the differential diagnosis of hirsutism, but patients typically will present with the features specific to these disorders. ABOUBBAKR ELNASHAR III. Idiopathic hirsutism ▪ hirsutism without hyperandrogenemia in eumenorrheic women who have no other clinical evidence suggesting PCOS or other hyperandrogenic endocrine disorder ▪ Some may have PCO on US and thus meet a Rotterdam criterion for “ovulatory PCOS” . ▪ 5% to 20% of hirsute women. being the second most common cause ▪ Among eumenorrheic women with mild hirsutism (a Ferriman–Gallwey hirsutism score of 8 to 15 in the United States, approximately half have idiopathic hirsutism ABOUBBAKR ELNASHAR
  12. 12. It is unclear whether idiopathic hirsutism is due to ▪ Altered androgen mechanism of action within the hair follicle (referred to as cutaneous hyperandrogenism) or to ▪ other alterations in hair biology. The routine assay of androgenic steroids other than testosterone has proven to be of little further diagnostic utility in most, but not all, populations ABOUBBAKR ELNASHAR 5. CLINICAL EVALUATION ▪ Women presenting with hirsutism should be evaluated with a focused history, physical examination, and appropriate investigations to DD among the possible etiologies (III-B). ▪ History ▪ Onset of hirsutism ▪ Symptoms of virilisation: clitoromegaly, deepening voice, male pattern alopecia ▪ Menstrual history ▪ Weight gain ▪ Drug history ▪ Family history of hyperandrogenism and/or hirsutism ABOUBBAKR ELNASHAR
  13. 13. ▪ Physical examination ▪ Severity of hirsutism (Ferriman-Gallwey score) ▪ Signs of hyperandrogenism: acne, hair thinning, seborrhea, AN ▪ Signs of virilisation: clitoromegaly, deepening voice, male pattern alopecia ▪ Signs of Cushing’s syndrome (moon facies, central obesity, acne, striae, proximal muscle weakness [difficulty standing from sitting position], thin skin, buffalo hump) ▪ Thyroid examination ABOUBBAKR ELNASHAR ▪ The modified Ferriman–Gallwey score ▪ The gold standard for evaluating hirsutism help assess response to treatment. ▪ 9 body areas most sensitive to androgen are assigned a score from 0 (no hair) to 4 (frankly virile), and these separate scores are summed to provide a hormonal hirsutism score ▪ United States and United Kingdom black or white women: 8 ▪ A score 8 represents excessive hair growth, with mild hirsutism <15, moderate 16 to 25, and severe >25 (II-2). Country USA, UK 8 Mediterranean, Hispanic, and Middle Eastern 9-10 South American 6 Han Chinese 2 ABOUBBAKR ELNASHAR
  14. 14. Ferriman–Gallwey hirsutism scoring system ABOUBBAKR ELNASHAR limitations ▪ Its subjective nature ▪ Failure to account for a locally high score that does not raise the total score to an abnormal extent ▪ lack of consideration of such androgen sensitive areas such as the sides of the face from the hairline to below the ear (sideburns) and the buttocks. ▪ even minimal degrees of unwanted hair are often associated with hyperandrogenemia when menstrual irregularity is present ABOUBBAKR ELNASHAR
  15. 15. 6. INVESTIGATIONS 1. Laboratory investigations for women with moderate to severe hirsutism should include total testosterone, although the benefit in mild hirsutism is questionable. 2. Additional testing is indicated for women with irregular menses and/or signs of hyperandrogenism or other endocrinopathies 3. Referral for evaluation reproductive endocrinologist 1. Virilisation 2. Serum testosterone or dehydroepiandrosterone sulfate levels more than twice the upper limit of normal 3. Signs or symptoms of Cushing’s syndrome 4. Early menstrual phase serum 17-hydroxyprogesterone levels >6 nmol/L (III-B). ABOUBBAKR ELNASHAR ▪ Total testosterone ▪ SHBG ▪ Dehydroepiandrosterone sulfate ▪ 17-OHP drawn in early menstrual phase to rule out CAH ▪ TSH ▪ Prolactin if galactorrhea or menstrual irregularity ▪ Pelvic ultrasound if ovarian neoplasm suspected ▪ MRI or CT if adrenal neoplasm suspected ▪ Cushing screen only if signs and symptoms of Cushing’s syndrome ABOUBBAKR ELNASHAR
  16. 16. Speroff et al, 2020 ABOUBBAKR ELNASHAR 7. TREATMENT ▪ The most effective therapy for hirsutism is multimodal & combines physical hair removal techniques & medical therapies. A. General: For hirsute women with obesity, including those with PCOS: ▪ Lifestyle changes ▪ long-term health sequelae of hyperandrogenism and PCOS: AUB, infertility, metabolic syndrome (III-B).. B. Specific I. Medical ▪ COC ▪ Antiandrogen ▪ Others II. Local ▪ Suppression of hair growth ▪ Removal of hair ABOUBBAKR ELNASHAR
  17. 17. I. Medical Treatments ▪ Indication: ▪ For most women with patient-important hirsutism despite cosmetic measures ▪ Duration: ▪ At least 6 months to ▪ see a significant improvement in hirsutism (II-2) ▪ change dose, switching to a new medication, or adding medication. ABOUBBAKR ELNASHAR COC: ▪ Indication: ▪ All patients experiencing hirsutism who desire treatment should be offered COC as first-line therapy, provided no contraindications (I-A). ▪ Type: ▪ All OCs equally effective, and the risk of side effects is low. ▪ For women with hirsutism at higher risk for VTE (e.g., those who are obese or over age 39 years), we suggest initial therapy with an OC containing the lowest effective dose of EE (usually 20 mcg) and a low-risk progestin ABOUBBAKR ELNASHAR
  18. 18. ABOUBBAKR ELNASHAR ▪ Antiandrogens ▪ Indications: can be used in conjunction with COC to enhance treatment efficacy (I-A). 1. moderate to severe hirsutism or to ensure an optimal response in milder hirsutism (I-A). 2. Severe hirsutism causing emotional distress and/or 3. women used OCs for 6 months and have not experienced sufficient improvement: initiating combination therapy with an OC and antiandrogen. ▪ we suggest against combination therapy as a standard first-line approach. ▪ For most women with hirsutism, we suggest against antiandrogen monotherapy as initial therapy (because of the teratogenic potential of these medications) unless these women use adequate contraception (Endocrine society, 2018) ABOUBBAKR ELNASHAR
  19. 19. ▪ Type: ▪ We do not suggest one antiandrogen over another ▪ we recommend against the use of flutamide because of its potential hepatotoxicity. ▪ Precaution: ▪ If a woman on anti-androgen therapy wishes to conceive, antiandrogen therapy should be stopped prior to discontinuing the use of contraception to prevent the potential feminization of a male fetus if pregnancy were to occur (III-B). ABOUBBAKR ELNASHAR ABOUBBAKR ELNASHAR
  20. 20. ▪ Other drug therapies ▪ We suggest against using insulin-lowering drugs for the sole indication of treating hirsutism. ▪ We suggest against using gnrh agonists except in women with severe forms of hyperandrogenemia (such as ovarian hyperthecosis) who have a suboptimal response to ocs and antiandrogens. ▪ We suggest against the use of topical antiandrogen therapy for hirsutism. ABOUBBAKR ELNASHAR II. Local treatment 1. Suppression of hair growth ▪ Eflornithine 13.9% (Vaniqa) cream ▪ Inhibits ornithine decarboxylase (an enzyme in hair dermal papilla that is essential for hair growth). ▪ For women who desire more rapid response to photoepilation, we suggest adding eflornithine topical cream during treatment. ABOUBBAKR ELNASHAR
  21. 21. 2. Direct Hair Removal Methods ABOUBBAKR ELNASHAR ABOUBBAKR ELNASHAR
  22. 22. ▪ Mechanical hair removal and/or topical therapy can be offered as first-line therapy or as an adjuvant to medical therapy (I-A). ▪ For women who then desire additional cosmetic benefit, we suggest adding direct hair removal methods ▪ For women with mild hirsutism and no evidence of an endocrine disorder, we suggest either approach. ▪ Only laser hair removal and electrolysis produce permanent hair reduction, and hair growth tends to recur after stopping medical therapy (II-2). ▪ For women who choose hair removal therapy, we suggest photoepilation for those whose unwanted hair is auburn, brown, or black, and we suggest electrolysis for those with white or blonde hair. ABOUBBAKR ELNASHAR ▪ For women of color who choose photoepilation treatment, we suggest using a long-wavelength, long pulse-duration light source such as Nd: YAG or diode laser delivered with appropriate skin cooling. ▪ Clinicians should warn Mediterranean and Middle Eastern women with facial hirsutism about the increased risk of developing PH with photoepilation therapy. We often suggest topical treatment or electrolysis over photoepilation with these patients. ABOUBBAKR ELNASHAR

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