HirsutismHirsutismAndAnd

VirilizationVirilization

Hirsutism:Hirsutism:-- Is the development ofIs the development ofandrogenandrogen--dependent terminal body hairdependent terminal body hairin a woman in places in which terminalin a woman in places in which terminalhair is normally not found, terminalhair is normally not found, terminalbody hairs are the stiff, pigmentedbody hairs are the stiff, pigmentedhairs normally seen in men on the face,hairs normally seen in men on the face,chest, abdomen, and back, which arechest, abdomen, and back, which arenot normal in women.not normal in women. Hirsutism affectHirsutism affectbetweenbetween 55 andand 1010 per cent of women ofper cent of women ofreproductive age .reproductive age .

Hirsutism:Hirsutism:-- Is the development ofIs the development ofandrogenandrogen--dependent terminal body hairdependent terminal body hairin a woman in places in which terminalin a woman in places in which terminalhair is normally not found, terminalhair is normally not found, terminalbody hairs are the stiff, pigmentedbody hairs are the stiff, pigmentedhairs normally seen in men on the face,hairs normally seen in men on the face,chest, abdomen, and back, which arechest, abdomen, and back, which arenot normal in women.not normal in women. Hirsutism affectHirsutism affectbetweenbetween 55 andand 1010 per cent of women ofper cent of women ofreproductive age .reproductive age .

VirilizationVirilization ::--Refers to the state in whichRefers to the state in whichandrogen levels are sufficientlyandrogen levels are sufficientlyhigh to cause not only hirsutism,high to cause not only hirsutism,but additional signs and symptomsbut additional signs and symptomssuch as deepening of the voice,such as deepening of the voice,breast atrophy, increased musclebreast atrophy, increased musclebulk, and clitoromegaly.bulk, and clitoromegaly.

VirilizationVirilization ::--Refers to the state in whichRefers to the state in whichandrogen levels are sufficientlyandrogen levels are sufficientlyhigh to cause not only hirsutism,high to cause not only hirsutism,but additional signs and symptomsbut additional signs and symptomssuch as deepening of the voice,such as deepening of the voice,breast atrophy, increased musclebreast atrophy, increased musclebulk, and clitoromegaly.bulk, and clitoromegaly.

There are two conditions characterizedThere are two conditions characterizedby generalized hair growth that do notby generalized hair growth that do notrepresent true hirsutism:represent true hirsutism:--

11--AndrogenAndrogen--independent hairindependent hair::-- which iswhich isthe soft vellus unpigmented hair that coversthe soft vellus unpigmented hair that coversthe entire body. In infants, this hair isthe entire body. In infants, this hair iscalled lanugo.called lanugo.

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There are two conditions characterizedThere are two conditions characterizedby generalized hair growth that do notby generalized hair growth that do notrepresent true hirsutism:represent true hirsutism:--

11--AndrogenAndrogen--independent hairindependent hair::-- which iswhich isthe soft vellus unpigmented hair that coversthe soft vellus unpigmented hair that coversthe entire body. In infants, this hair isthe entire body. In infants, this hair iscalled lanugo.called lanugo.

. .

22--HypertrichosisHypertrichosis::-- Hypertrichosis is theHypertrichosis is theterm used to describe the excessive growthterm used to describe the excessive growthof androgenof androgen--independent hair which isindependent hair which isvellus, prominent in nonvellus, prominent in non--sexual areas, andsexual areas, andmost commonly familial or caused bymost commonly familial or caused bysystemic disorders (hypothyroidism,systemic disorders (hypothyroidism,anorexia nervosa, malnutrition, porphyria,anorexia nervosa, malnutrition, porphyria,and dermatomyositis), orand dermatomyositis), ormedications(phenytoin, penicillamine,medications(phenytoin, penicillamine,diazoxide, minoxidil, or cyclosporine)diazoxide, minoxidil, or cyclosporine)or as a paraneoplastic syndrome in someor as a paraneoplastic syndrome in somepatients with cancer.patients with cancer.

22--HypertrichosisHypertrichosis::-- Hypertrichosis is theHypertrichosis is theterm used to describe the excessive growthterm used to describe the excessive growthof androgenof androgen--independent hair which isindependent hair which isvellus, prominent in nonvellus, prominent in non--sexual areas, andsexual areas, andmost commonly familial or caused bymost commonly familial or caused bysystemic disorders (hypothyroidism,systemic disorders (hypothyroidism,anorexia nervosa, malnutrition, porphyria,anorexia nervosa, malnutrition, porphyria,and dermatomyositis), orand dermatomyositis), ormedications(phenytoin, penicillamine,medications(phenytoin, penicillamine,diazoxide, minoxidil, or cyclosporine)diazoxide, minoxidil, or cyclosporine)or as a paraneoplastic syndrome in someor as a paraneoplastic syndrome in somepatients with cancer.patients with cancer.

Causes of hirsutism

CommonCommonIdiopathic hirsutism.Idiopathic hirsutism.--11

22--Polycystic ovary syndrome.Polycystic ovary syndrome.

CommonCommonIdiopathic hirsutism.Idiopathic hirsutism.--11

22--Polycystic ovary syndrome.Polycystic ovary syndrome.

UncommonUncommon11--Drug:Drug:-- Danazol, Oral contraceptives containingDanazol, Oral contraceptives containingandrogenic progestins.androgenic progestins.22--Congenital adrenal hyperplasiaCongenital adrenal hyperplasia (most often(most often 2121--hydroxylase deficiency( .hydroxylase deficiency( .33--Hyperthecosis.Hyperthecosis.44--Ovarian tumorsOvarian tumors::-- SertoliSertoli--Leydig cell tumors .Leydig cell tumors .

GranulosaGranulosa--theca cell tumors.theca cell tumors.HilusHilus--cell tumors.cell tumors.

55--Adrenal tumors.Adrenal tumors.66--Severe insulin resistance syndromes.Severe insulin resistance syndromes.77--Hyperprolactinemia.Hyperprolactinemia.88--Cushing's syndromeCushing's syndrome..

UncommonUncommon11--Drug:Drug:-- Danazol, Oral contraceptives containingDanazol, Oral contraceptives containingandrogenic progestins.androgenic progestins.22--Congenital adrenal hyperplasiaCongenital adrenal hyperplasia (most often(most often 2121--hydroxylase deficiency( .hydroxylase deficiency( .33--Hyperthecosis.Hyperthecosis.44--Ovarian tumorsOvarian tumors::-- SertoliSertoli--Leydig cell tumors .Leydig cell tumors .

GranulosaGranulosa--theca cell tumors.theca cell tumors.HilusHilus--cell tumors.cell tumors.

55--Adrenal tumors.Adrenal tumors.66--Severe insulin resistance syndromes.Severe insulin resistance syndromes.77--Hyperprolactinemia.Hyperprolactinemia.88--Cushing's syndromeCushing's syndrome..

HyperthecosisHyperthecosis refers to the presence ofrefers to the presence ofnests of luteinized theca cells in thenests of luteinized theca cells in theovarian stroma due to differentiation ofovarian stroma due to differentiation ofthe ovarian interstitial cells intothe ovarian interstitial cells intosteroidogenically active luteinizedsteroidogenically active luteinizedstromal cells . These nests or islands ofstromal cells . These nests or islands ofluteinized theca cells are scatteredluteinized theca cells are scatteredthroughout the stroma of the ovary,throughout the stroma of the ovary,rather than being confined to areasrather than being confined to areasaround cystic follicles as in thearound cystic follicles as in thepolycystic ovary syndromepolycystic ovary syndrome

HyperthecosisHyperthecosis refers to the presence ofrefers to the presence ofnests of luteinized theca cells in thenests of luteinized theca cells in theovarian stroma due to differentiation ofovarian stroma due to differentiation ofthe ovarian interstitial cells intothe ovarian interstitial cells intosteroidogenically active luteinizedsteroidogenically active luteinizedstromal cells . These nests or islands ofstromal cells . These nests or islands ofluteinized theca cells are scatteredluteinized theca cells are scatteredthroughout the stroma of the ovary,throughout the stroma of the ovary,rather than being confined to areasrather than being confined to areasaround cystic follicles as in thearound cystic follicles as in thepolycystic ovary syndromepolycystic ovary syndrome

Basic Approach to the patientBasic Approach to the patientBasic Approach to the patientBasic Approach to the patient

History:History:--Menstrual history.Menstrual history.Hyperandrogenic symptoms.Hyperandrogenic symptoms.Weight historyWeight history ..Medication history .Medication history .Family history .Family history .

History:History:--Menstrual history.Menstrual history.Hyperandrogenic symptoms.Hyperandrogenic symptoms.Weight historyWeight history ..Medication history .Medication history .Family history .Family history .

Physical examination :- The physicalexamination provides information aboutthe extent of hirsutism and sometimesabout its cause.

Physical examination :- The physicalexamination provides information aboutthe extent of hirsutism and sometimesabout its cause.

Ferriman-Gallwey score

Investigations:Investigations:--AA--Laboratory Testing :Laboratory Testing :--11--Serum androgensSerum androgens ::-- They are sufficient toThey are sufficient toexclude androgenexclude androgen--secreting tumors in most women;secreting tumors in most women;specifically, values belowspecifically, values below ((55..22 nmol/L)nmol/L) excludeexcludeovarian or adrenal tumors These values also tend toovarian or adrenal tumors These values also tend toexclude ovarian hyperthecosis. Most women withexclude ovarian hyperthecosis. Most women withPCOS have serum testosterone concentrationsPCOS have serum testosterone concentrationsbelowbelow ((55..22 nmol/L),nmol/L), and sometimes normal; womenand sometimes normal; womenwith idiopathic hirsutism are even more likely towith idiopathic hirsutism are even more likely tohave normal values.have normal values.

Investigations:Investigations:--AA--Laboratory Testing :Laboratory Testing :--11--Serum androgensSerum androgens ::-- They are sufficient toThey are sufficient toexclude androgenexclude androgen--secreting tumors in most women;secreting tumors in most women;specifically, values belowspecifically, values below ((55..22 nmol/L)nmol/L) excludeexcludeovarian or adrenal tumors These values also tend toovarian or adrenal tumors These values also tend toexclude ovarian hyperthecosis. Most women withexclude ovarian hyperthecosis. Most women withPCOS have serum testosterone concentrationsPCOS have serum testosterone concentrationsbelowbelow ((55..22 nmol/L),nmol/L), and sometimes normal; womenand sometimes normal; womenwith idiopathic hirsutism are even more likely towith idiopathic hirsutism are even more likely tohave normal values.have normal values.

Moderately elevated (or higher) serumModerately elevated (or higher) serumandrogen concentrations,androgen concentrations,eg, serum total testosterone values aboveeg, serum total testosterone values above((55..22 nmol/L)nmol/L)serum free testosterone values aboveserum free testosterone values above ((00..0707nmol/L)nmol/L) ;;and serum dehydroepiandrosterone sulfateand serum dehydroepiandrosterone sulfate(DHEA(DHEA--S) values aboveS) values above ((1313..66 µmol/L)µmol/L) ininyoung women raise the possibility of anyoung women raise the possibility of anandrogenandrogen--secreting tumors.secreting tumors.

Moderately elevated (or higher) serumModerately elevated (or higher) serumandrogen concentrations,androgen concentrations,eg, serum total testosterone values aboveeg, serum total testosterone values above((55..22 nmol/L)nmol/L)serum free testosterone values aboveserum free testosterone values above ((00..0707nmol/L)nmol/L) ;;and serum dehydroepiandrosterone sulfateand serum dehydroepiandrosterone sulfate(DHEA(DHEA--S) values aboveS) values above ((1313..66 µmol/L)µmol/L) ininyoung women raise the possibility of anyoung women raise the possibility of anandrogenandrogen--secreting tumors.secreting tumors.

22--Serum prolactin .Serum prolactin .33--Serum luteinizing hormone (LHSerum luteinizing hormone (LH) :) :--Women with PCOS tend to have elevatedWomen with PCOS tend to have elevatedserum LH concentrations and normal or lowserum LH concentrations and normal or lowserum FSH concentrations.serum FSH concentrations.44--OH progesteroneOH progesterone ::--congenital adrenalcongenital adrenalhyperplasia, or to know a specific etiologichyperplasia, or to know a specific etiologicdiagnosis.diagnosis.55--Testing for Cushing's syndromeTesting for Cushing's syndrome ..

22--Serum prolactin .Serum prolactin .33--Serum luteinizing hormone (LHSerum luteinizing hormone (LH) :) :--Women with PCOS tend to have elevatedWomen with PCOS tend to have elevatedserum LH concentrations and normal or lowserum LH concentrations and normal or lowserum FSH concentrations.serum FSH concentrations.44--OH progesteroneOH progesterone ::--congenital adrenalcongenital adrenalhyperplasia, or to know a specific etiologichyperplasia, or to know a specific etiologicdiagnosis.diagnosis.55--Testing for Cushing's syndromeTesting for Cushing's syndrome ..

BB--Radiological Testing :Radiological Testing :--11--Pelvic ultrasonographyPelvic ultrasonography22--Abdominal CT or MRI Testing:Abdominal CT or MRI Testing:--

CC--Laparoscopy or laparotomyLaparoscopy or laparotomyDD--Ovarian and adrenal vein sampling :Ovarian and adrenal vein sampling :--EE--GnRH agonist testing :GnRH agonist testing :--GnRH agonist testing has been utilized as aGnRH agonist testing has been utilized as ameans of making a specific diagnosis ofmeans of making a specific diagnosis ofovarian hyperandrogenism.ovarian hyperandrogenism. ِ◌ ِ◌

BB--Radiological Testing :Radiological Testing :--11--Pelvic ultrasonographyPelvic ultrasonography22--Abdominal CT or MRI Testing:Abdominal CT or MRI Testing:--

CC--Laparoscopy or laparotomyLaparoscopy or laparotomyDD--Ovarian and adrenal vein sampling :Ovarian and adrenal vein sampling :--EE--GnRH agonist testing :GnRH agonist testing :--GnRH agonist testing has been utilized as aGnRH agonist testing has been utilized as ameans of making a specific diagnosis ofmeans of making a specific diagnosis ofovarian hyperandrogenism.ovarian hyperandrogenism. ِ◌ ِ◌

Preoperative preparation:Preoperative preparation:--Treatment ofhirsutism

Nonpharmacologic Therapy:Nonpharmacologic Therapy:--11--Hair removal :Hair removal :-- Shaving , ChemicalShaving , Chemicaldepilatories and bleaching ,and waxdepilatories and bleaching ,and waxare all easy and cheep. Electrolysis isare all easy and cheep. Electrolysis issafe and effective but expensive. Lasersafe and effective but expensive. Lasertreatment, although expensive, istreatment, although expensive, iseffective and can often result ineffective and can often result inpermanent reduction in hair growth.permanent reduction in hair growth.

Nonpharmacologic Therapy:Nonpharmacologic Therapy:--11--Hair removal :Hair removal :-- Shaving , ChemicalShaving , Chemicaldepilatories and bleaching ,and waxdepilatories and bleaching ,and waxare all easy and cheep. Electrolysis isare all easy and cheep. Electrolysis issafe and effective but expensive. Lasersafe and effective but expensive. Lasertreatment, although expensive, istreatment, although expensive, iseffective and can often result ineffective and can often result inpermanent reduction in hair growth.permanent reduction in hair growth.

Pharmacologic Therapy:Pharmacologic Therapy:--11-- Eflornithine hydrochlorideEflornithine hydrochloride cream :cream :--is a topical drug ,is an inhibitor of hairis a topical drug ,is an inhibitor of hairgrowth, not a depilatory, and must be usedgrowth, not a depilatory, and must be usedindefinitely to prevent regrowthindefinitely to prevent regrowth..

22--Hormonal therapy:Hormonal therapy:--Oral contraceptivesOral contraceptives

Pharmacologic Therapy:Pharmacologic Therapy:--11-- Eflornithine hydrochlorideEflornithine hydrochloride cream :cream :--is a topical drug ,is an inhibitor of hairis a topical drug ,is an inhibitor of hairgrowth, not a depilatory, and must be usedgrowth, not a depilatory, and must be usedindefinitely to prevent regrowthindefinitely to prevent regrowth..

22--Hormonal therapy:Hormonal therapy:--Oral contraceptivesOral contraceptives

33--Antiandrogen therapyAntiandrogen therapy . .AA--SpironolactoneSpironolactone ::--The usual dose isThe usual dose is 2525--100100 mg givenmg givenonce daily. The benefit was noticeableonce daily. The benefit was noticeablewithin two months, reached a peak atwithin two months, reached a peak atsix months, and was maintained atsix months, and was maintained at 1212

months.months.

33--Antiandrogen therapyAntiandrogen therapy . .AA--SpironolactoneSpironolactone ::--The usual dose isThe usual dose is 2525--100100 mg givenmg givenonce daily. The benefit was noticeableonce daily. The benefit was noticeablewithin two months, reached a peak atwithin two months, reached a peak atsix months, and was maintained atsix months, and was maintained at 1212

months.months.

BB--Flutamide :Flutamide :-- Flutamide, also inhibitsFlutamide, also inhibitstestosterone binding to its receptors, dose :testosterone binding to its receptors, dose :-- ((250250mg BID).mg BID).

CC--Finasteride :Finasteride :-- Finasteride inhibitsFinasteride inhibits 55--alphaalpha--reductase, the enzyme that catalyzes thereductase, the enzyme that catalyzes theconversion of testosterone to dihydrotestosteroneconversion of testosterone to dihydrotestosterone.Compared with spironolactone, finasteride is as.Compared with spironolactone, finasteride is asor less effective.Finasteride lowers hirsutismor less effective.Finasteride lowers hirsutismscores better when given in combination with anscores better when given in combination with anoral contraceptive. Dose of finasteride (oral contraceptive. Dose of finasteride (55mg/day).mg/day).

BB--Flutamide :Flutamide :-- Flutamide, also inhibitsFlutamide, also inhibitstestosterone binding to its receptors, dose :testosterone binding to its receptors, dose :-- ((250250mg BID).mg BID).

CC--Finasteride :Finasteride :-- Finasteride inhibitsFinasteride inhibits 55--alphaalpha--reductase, the enzyme that catalyzes thereductase, the enzyme that catalyzes theconversion of testosterone to dihydrotestosteroneconversion of testosterone to dihydrotestosterone.Compared with spironolactone, finasteride is as.Compared with spironolactone, finasteride is asor less effective.Finasteride lowers hirsutismor less effective.Finasteride lowers hirsutismscores better when given in combination with anscores better when given in combination with anoral contraceptive. Dose of finasteride (oral contraceptive. Dose of finasteride (55mg/day).mg/day).

DD--Cyproterone acetate:Cyproterone acetate:--EE--ketoconazole :ketoconazole :-- Is Antifungal Agent, itIs Antifungal Agent, itact on steriodogenic cytocrom enzyme inact on steriodogenic cytocrom enzyme inthe liver ,and decrease androstenedione andthe liver ,and decrease androstenedione andfree testosterone level, if give at a dose offree testosterone level, if give at a dose of((200200 mg/day).mg/day).Side effect are dry skin, scalp hair loss, andSide effect are dry skin, scalp hair loss, andhepatotoxic in largev doses (hepatotoxic in largev doses (400400--12001200mg/day).mg/day).

DD--Cyproterone acetate:Cyproterone acetate:--EE--ketoconazole :ketoconazole :-- Is Antifungal Agent, itIs Antifungal Agent, itact on steriodogenic cytocrom enzyme inact on steriodogenic cytocrom enzyme inthe liver ,and decrease androstenedione andthe liver ,and decrease androstenedione andfree testosterone level, if give at a dose offree testosterone level, if give at a dose of((200200 mg/day).mg/day).Side effect are dry skin, scalp hair loss, andSide effect are dry skin, scalp hair loss, andhepatotoxic in largev doses (hepatotoxic in largev doses (400400--12001200mg/day).mg/day).

Other therapiesOther therapies::--11--GonadotropinGonadotropin--releasing hormone agonistreleasing hormone agonist::--22--InsulinInsulin--lowering agents :lowering agents :-- Both metforminBoth metforminand rosiglitazone can be modestly effective inand rosiglitazone can be modestly effective inthe treatment of hirsutism associated withthe treatment of hirsutism associated withPCOS. Both agents can restore ovulatoryPCOS. Both agents can restore ovulatorycycles and reduce circulating testosterone andcycles and reduce circulating testosterone andandrostenedione in some women with PCOS.androstenedione in some women with PCOS.

Other therapiesOther therapies::--11--GonadotropinGonadotropin--releasing hormone agonistreleasing hormone agonist::--22--InsulinInsulin--lowering agents :lowering agents :-- Both metforminBoth metforminand rosiglitazone can be modestly effective inand rosiglitazone can be modestly effective inthe treatment of hirsutism associated withthe treatment of hirsutism associated withPCOS. Both agents can restore ovulatoryPCOS. Both agents can restore ovulatorycycles and reduce circulating testosterone andcycles and reduce circulating testosterone andandrostenedione in some women with PCOS.androstenedione in some women with PCOS.