Anda di halaman 1dari 13

7

OVERVIEW

AMENORRHOEA
Amenorrhoea is defined as the absence of menstruation . It may be classified as either primary amenorrhea (very rare <0.1%), or secondary amenorrhea which is commonly encountered.

Primary amenorrhoea: bsence of menstruation by 14 years of a!e" without development of secondary sexual characteristics bsence of menstruation by 16 years of a!e regardless of secondary sex characteristic development

Secondary amenorrhoea# is cessation of menstruation > six months (or a 3 cycle interval), in a woman in the reproductive a!e who has been previously menstruatin!, in absence of pre!nancy. Physiologic 2ry amenorrhoea" may occur in association with anovulation as in the few cycles followin! menarche, the few years precedin! menopause, and in some women durin! lactation. Hypomenorrhoea: menstrual bleedin! which is sli!ht in amount or short in duration, or both. Oligomenorrhoea: infre$uent menstruation, i.e. too lon! menstrual cycles, % &' days apart.

N.B.; (oth )li!omenorrhea and *ypomenorrhea may be constitutional or endocrine in aetiolo!y. +he investi!ations and treatment is the same as amenorrhea but the pro!nosis is better. Anatomic and physiological re !irements "or normal menstr!ation: A " % & ' Patent outflo! tract throu!h which the menstrual flow is conducted from the endometrium outwards. Oestrogen # progesterone responsi$e endometrium" that proliferates and des$uamates on cyclic basis. O$arian steroids (oestro!en-,- and pro!esterone-.)" available in the appropriate $uantity, se$uence, and timely secretion by the dominant ovarian follicle and the corpus luteum (/0). Pituitary gonadotropin (12* 3 0*) in appropriate se$uence and $uantities from the anterior pituitary. Hypothalamic pulsatile secretion of (n)H dependin! on the feedbac4 steroid si!nals from the ovary which modifies the anterior pituitary !onadotrope response to the 5n6*.

AE#IO$O%& O' AMENORRHOEA

Reprod!cti(e o!t"lo) tract disorders - Imperforate hymen - +ransverse septum va!inal

O(arian disorders
- 5onadal dys!enesis - .remature failure - 6esistant syndrome ovarian. ovary -

Pit!itary disorders
.ituitary adenomas .ituitary necrosis

Hypothalamic mal"!nction
- ,:cessive stress - ,:cessive e:ercise - ,:cessive loss wei!ht

- 7ullerian a!enesis

- +esticular femini8ation
sherman9s syndrome

- /raniopharyn!ionma - ;allmann9s syndrome

novulation (./)2)

I* VA%INA$ AN+ ,#ERINE -A,SES .+ISOR+ERS O' #HE O,#'$OW #RA-#/: A/ Imper"orate hymen: * * * n imperforate hymen is the commonest cause of crypto*menorrhea (false amenorrhea). It occurs in around 0.1% of newborn females due to absent orifice in the vaginal hymen. It presents clinically as 1ry amenorrhea in a !irl (< months to 1 year after her e:pected a!e of menarche), with cyclic lower abdominal pain, and normally developed -ry se:ual characters. fter menarche, menstrual blood will accumulate behind the imperforate hymen formin! a haematocolpos which may be seen as a bul!e at the hymeneal rin! with a sli!ht bluish coloration. If lar!e it can be palpated at PR examination, and dia!nosis confirmed by ultrasono!raphy.

0/ #rans(erse (aginal sept!m: =a!inal septum is the second most common cause for crypto*menorrhea. )ne or more vaginal septae can occur at any level between the hymeneal rin! and the cervi:, leadin! to occlusion of the lower, middle, or upper se!ment of the va!ina, with formation of a haematocolpos. fter menarche, the patient will present with 1ry amenorrhea, cyclic lower abdominal pain, and well developed -ry se:ual characters. +he presentation is similar to that of imperforate hymen.

-/ M!llerian agenesis: /omplete or partial a!enesis of the m>llerian structures (7ayer-6o4itans4y-;uster-*auser syndrome), is the most common congenital anomaly of the uterus, accountin! for about -0% of cases with primary amenorrhoea. It occurs in around 1#?000 ?<@@ female births. +he underlyin! mechanism involves unwanted e:posure to anti mullerian hormone ( 7*) with failed fusion of the mullerian ducts. *ypothalamic-pituitary-ovarian a:is is intact with normal ovarian steroid hormone production, and normal development of secondary se:ual characters. 1A& of patients may have associated mesonephric abnormalities (urinary tract anomalies), and 1-% may have associated s4eletal anomalies.

+/ -omplete androgen insensiti(ity syndrome: (Testicular feminisation) +his is an X lin!ed recessive disorder in which male subjects with 46 XY 4aryotype appear phenotypically as females that will present after puberty by 1ry amenorrhea. .resence of the Y chromosome will result in presence of the mullerian inhibitin! factor (MIF) leadin! to failure of development of the mullerian system (uterus, cervi: and upper 1A& va!ina). .resence of Y chromosome also results in normal male testosterone levels and elevated 0* values. defect in peripheral andro!en receptors renders them resistant to testosterone action with failure to develop testosterone dependent male se:ual characteristics. +he e:ternal !enitalia will develop typically as a female with blind ended va!ina. t puberty, breast development occurs, but immature pale areola and sparse pubic and a:illary hairs. 7ale 5onadal tissue may be present in the labia or in!uinal canal, but incapable of spermato!enesis. 5onadectomy must be performed in such patients as they carry a -0% ris4 of !onadoblastoma however it is usually deferred until after puberty.

E/ Asherman1s syndrome: (intrauterine synaechae) Secondary amenorrhea due to intrauterine synaechae caused by ac$uired scarrin! of the endometrium. It may occurs followin! vi!orous curetta!e, as for retained products of conception, or -ry to intrauterine infection (post-abortive or postpartum), and rarely due to +.(. endometritis. +he dia!nosis is su!!ested by history, suspected by the absence of a normal uterine stripe on pelvic B.2. and confirmed by hysterosalpin!o!raphy (*25) and or hysteroscopy.

II* OVARIAN +ISOR+ERS: A/ #!rner syndrome: (Gonadal Agenesis) +urner syndrome accounts for almost 1A& of cases of 1ry amenorrhoea. n underlyin! chromosomal de ect occurs in which an @ chromosome will be missin! (?'-@ !onadal dys!enesis), and the ovaries will be replaced with fibrous tissue (strea! gonads) that does not produce enou!h oestro!en, inspite of elevated 12* and 0* levels +hypergonadotropic 1ry amenorrhea . !bsence o the Y chromosome will allow development of the va!ina, uterus, and fallopian tubes normally until puberty when oestro!en-induced maturation fails to occur. +he ovaries are represented by small strea4 !onads, the uterus is infantile in si8e, the cervi: and the va!ina are normally canali8ed. .henotypic characteristics include" low hair line, short stature, webbed nec4, shield chest, and increased carryin! an!le at the elbow. /ardiac and renal anomalies should be ruled out . In subCects with a mosaic 4aryotype (?', @A?<, @@), spontaneous menstruation and pre!nancy may sometimes occur (-%-'% of cases). It is hypergonadotropic 2ry amenorrhea due to e:haustion or depletion of oocytes that occurs before the a!e of ?0 years leadin! to ovarian failure and premature menopause. /auses include" 1. -. &. "diopathic, associated with autoimmune ovarian destruction !aryotypic abnormalities (loss of a small portion of the @ chromosome) "nduced by radiation therapy or chemotherapy.

0/ Premat!re o(arian "ail!re: -

-/ Resistant o(ary syndrome: +his type of hypergonadotropic 2ry amenorrhea occurs when viable follicles within the ovary fail to respond to pituitary !onadotropin due to a defect in their #$%&'$ receptor comple:. In few cases the condition is temporary and some may ovulate and conceive.

+/ Polycystic o(ary syndrome .P-OS/ ./)2 describes a triad of chronic anovulation (or oli!o-ovulation), obesity, and hirsutism (andro!en e:cess). Dia!nosis is made by inclusion of at least two of the followin! criteria" 1. 7enstrual irre!ularity si!nifyin! oli!o-or anovulation -. Bltrasound characteristic picture of multiple small peripherally arran!ed cysts (strin! of pearls) &. /linical or laboratory evidence of hyperandro!enism (hirsutism, elevated andro!en levels, elevated 0* levels and low-normal 12* levels). E/ Other ca!se: (ilateral sur!ical removal of the ovaries (durin! hysterectomy, or in some cases of breast carcinoma). Destruction of the ovaries (post irradiation E chemotherapy)

III* +ISOR+ERS O' #HE AN#ERIOR PI#,I#AR& %$AN+ A/ Pit!itary adenomas: e*g*2 Prolactinoma .rolactinomas are the commonest pituitary disorder responsible for amenorrhoea (F0% of cases). .rolactinomas result in hyperprolactinaemia which in turn suppresses hypothalamic 5n6* secretion, leadin! to low !onadotropin and ,- concentrations. +hey are responsible for al most -0% of cases of -ry amenorrhoea. 2erum prolactin concentrations !enerally correlate with pituitary tumour si8e (microadenomas <10 mm si8e, or macroadenomas %10 mm si8e).

&

0/ Empty sella syndrome: n empty sella refers to an enlar!ed sella turcica that is not entirely filled with pituitary tissue. It occurs mostly due to a defect in the diaphra!ma sella that allows cerebrospinal fluid (/21) pressure to enlar!e the sella. +he condition is typically detected by 76I, and is not associated with hypopituitarism or any other type of hormone disorder

-/ Pit!itary ins!""iciency: 2heehanGs syndrome (pituitary necrosis followin! severe postpartum haemorrha!e leadin! to hypopituitarism and hypo!onadotropic amenorrhoea). 6adiation necrosis, pituitary infarctions, and non-lactotrophic adenomas. Infiltrative lesions of the pituitary !land, such as lymphocytic hypophysitis.

IV* -NS AN+ H&PO#HA$AMI- +ISOR+ERS *ypothalamic amenorrhoea occurs due to decreased (n)H pulse fre,uency and amplitude leadin! to decreased pituitary !onadotropin secretion, absent midcycle 0* sur!es, chronic anovulation, and low serum ,- concentrations (hypogonadotropic hypogonadism . /ommon causes include"

1- 'xercise and stress:


minimum of around -0% of body fat by wei!ht is re$uired for the initiation of menarche and maintenance of menses. 7enstrual irre!ularities are therefore common in female competitive athletes, in which an added stress of performance may result in increased levels of circulatin! endorphins which can reduce 5n6* production from the hypothalamus. (motionally stressful events such as those related to wor4, family relationships, study, travel, death or illness of a close family member, may all cause amenorrhea.

2- Anorexia and !eight loss:


6apid wei!ht loss below 1'--0% of ideal body wei!ht is often associated with -ry amenorrhoea. )norexia nervosa is an e:treme form of this condition that may affect 1% of youn! women. (ulimia (induced vomitin!) may be present in '0% of cases.

.- &rug*induced amenorrhea: +his may occur with the use of dru!s such as"
.ro!estins (Depot-.rovera), dana8ol, and 5n6* a!onists nti-psychotics and tri-cyclic anti-depressants (stimulate prolactin secretion) nti-hypertensives such as reserpine and methyldopa, in addition to opiates and barbiturates. contraceptive pills. +he condition is temporary and normal menses is usually resumed in --< months.

4- Post pill amenorrhoea: It may occur in nearly 1% of women discontinuin! combined oral /- Pseudocyesis +false pregnancy : is an interestin! condition that may rarely occur in women desirous
of pre!nancy. +he aetiolo!y is un4nown but there appears to be a voluntary alteration of hypothalamic function. .rolactin levels may be elevated enou!h to cause !alactorrhea.

6-

0nfiltrati$e lesions of hypothalamus +rare : - 0ymphoma, 0an!erhans cell histiocytosis, and sarcoidosis can result in decreased 5n6* secretion, low or normal serum 12* and 0*, and amenorrhea. 7ost women with infiltrative disease of the hypothalamus who have amenorrhoea will have one or more neurolo!ic symptoms as severe headache, chan!e in personality, or mar4ed mood chan!es.

1-

2allmann 3yndrome: +%ongenital (n )H deficiency - .rimary amenorrhea due to con!enital 5n 6* deficiency occurrin! in association with infantile sexual de$elopment and anosmia (failure of neuronal mi!ration of olfactory placode in the nose)

V* EN+O-RINE +ISOR+ERS: Hypothyroidism: +2* is usually elevated which results in an elevated prolactin level. %ushing4s syndrome: Increased adrenal activity leads to a hyperandro!enic state.

-lassi"ication o" amenorrhoea according to gonadotropin prod!ction


"y#er$onadotro#%c amenorrhea; elevated !onadotropins (12* % -0 IBA0, and 0* % ?0 IBA0) &u$onadotro#%c amenorrhea; normal !onadotropin levels (12* and 0* levels of '--0 IBA0) "y#o$onadotro#%c amenorrhea2 low !onadotropin levels (12* and 0* < ' IBA0)

-$INI-A$ EVA$,A#ION O' A -ASE O' AMENORRHOEA 3 O$I%OMENORRHOEA


A/ HIS#OR& #A4IN% IN AMENORRHOEA 0n cases of primary Amenorrhoea: Developmental history" !rowth spurt, breast development, and pubic hair !rowth. .resence or absence of cyclic symptoms (cryptomenorrhea). *istory of chronic illness. ,:cessive wei!ht loss or presence of an eatin! disorder. ,:cessive e:ercise. *istory or family history of anosmia (deficient smell senses *allmann 'yndrome). 0n cases of secondary Amenorrhoea are: !e of onset of menarche. 7enstrual, contraceptive and reproductive history .ast medical and sur!ical history. .resence of menopausal symptoms. 1amily history of premature menopause. /urrent medications. Development of virili8in! si!ns or !alactorrhea. .sycholo!ical history. 6ecent stressful events (past or present history of depression or an eatin! disorder).

0/ E5AMINA#ION O' A -ASE O' AMENORRHEA: +eneral examination, for female phenotypic characters. (valuation of pubertal development, includin! current hei!ht, wei!ht, and arm span (normal arm span for adults is within ' cm of hei!ht). -easurement of the body mass index ((7I H wei!ht in 4! A hei!ht in 7 s$uared). Iormal (7I for hei!ht H -< or less, overwei!ht# -J--K, )besity with e:cessive body fat# %-K. )ssessment of breast and pubic hair development by +anner sta!in! (see puberty)

'

+enital examination" clitoral si8e, intactness of the hymen, depth of the va!ina (not in vir!ins), and presence of a cervi:, uterus, and ovaries. If the va!ina cannot be penetrated with a fin!er, rectal e:amination may allow evaluation of the internal or!ans. (xamination of the s!in for hirsutism, acne, striae, and increased pi!mentation. In cases with Turner syndrome the blood pressure should be measured in both arms because it is associated with an increased incidence of coarctation of the aorta.

-/ INVES#I%A#IONS IN A -ASE O' AMENORRHEA: '. "ormonal (ro %le) 'erum h.+" to e:clude possible pre!nancy as the commonest cause of -ry amenorrhea. 'erum Prolactin, as hyperprolactinaemia is a common cause of -ry amenorrhea. Pituitary +onadotropins, 12*-0*" ,levated levels will confirm premature ovarian failure, or resistant ovary. 6educed levels indicate a pituitary or hypothalamic disorder.

/varian steroids namely 'erum (0, 0ow levels in !onadal dys!enesis, premature ovarian failure, and menopause, while normal or elevated levels are found in ./)2. )ndrogen profile, amenorrhea associated with hyperandro!enism" e.!." - ./)2 (the commonest cause), /ushin! syndrome and / *, andro!en-secretin! ovarian tumours (androblastoma), and testicular femini8ation (male andro!en levels) are all rare causes . Thyroid function tests" +2*-+&-+?" should be performed in all patients with amenorrhea. +nR$ stimulation tests may be helpful in distin!uishin! between a pituitary and hypothalamic cause. *. (el+%c ,ltrasound) .elvic ultrasound is best performed via +ransva!inal route (+=2). In vir!ins it may be either performed transabdominal (+ 2) with a full bladder as a prere$uisite, or transrectal (+62). ,:amination of A 5he uterus1 - Its presence e:cludes mullerian a!enesis. - ssessment of body to cervi: ratio" (-#1 is normal 1#1 denotes infantile uterus). - ssessment of endometrial thic4ness which correlates with oestro!en levels, and echo!enicity that correlates with proliferative or secretory activity. " 5he o$aries: - +heir presence e:cludes !onadal dys!enesis and strea4 !onads. - +heir si8e and confi!uration will e:clude ./)2, and functional cysts. - +o monitor follicular activity in suspected anovulatory cases. -. .aryoty#e) .hoto!raphin! the chromosomes to enable their countin! and structural e:amination, usin! lymphocytes or fibroblasts, is indicated in women with" - Primary amenorrhoea" suspected +urner syndrome (?' @)) or testicular femini8ation (?< @L) - 'econdary amenorrhoea due to premature ovarian failure in a women < ?0 years a!e 4. !uto%mmune screen) may detect ovarian antibodies in women with premature ovarian failure.

<

/. 012M3I scann%n$# 7ay be useful in determinin! the intracranial lesions, as pituitary adenomas.

#REA#MEN# O' AMENORRHEA


+he aim may be" to re-establish cyclic bleedin!, to maintain a normal uterine si8e, or to help proper development of secondary se:ual characters. In some treatment of infertility will be the achieved !oal. 6* -yclic hormone replacement therapy .HR#/2 - %yclic combined oestrogen6gestagen (as that in )/.) for -1 days each month will help to induce re!ular cycles and prevent the deleterious se$uelae of oestro!en deprivation. It is suitable in cases with premature ovarian failure, strea4 !onads, hypoplastic uterus, and ./)2. - %yclic natural or synthetic progesterone therapy (J-10 days every month) may be enou!h to induce re!ular cycles whenever the endometrium is properly primed by oestro!en as in some cases of ./) 7* +r!gs "or ind!ction o" o(!lation (see infertility for treatment of anovulation)# - %lomiphene citrate +%% oral tablets in cases with normal 12* levels (eu!onadotropic) - 0-7- gonadotropin therapy +H7(6h%( in hypothalamic or pituitary amenorrhea with low 12* levels (*ypo!onadotropic) desirous for fertility. 8* +r!gs "or treatment o" Hyperprolactinaemia: (pituitary hyperplasia or microadenomas) - Dopamine a!onists (bromocryptine), 1-- tablets daily (?-< wee4s) to restore normal prolactin levels - /aber!oline, 1A- tablet once or twice wee4ly, is associated with less side effects (see !alactorrhea) 9* +r!gs to restore thyroid disorders2 treated either with either - +hyroid e:tract (eltro:in) in cases of hypothyroidism ntithyroid dru!s (thiouracil) in thyroid hyperfunction and thyroto:icosis. :* Pit!itary +isorders: a) (%tu%tary %nsu %c%ency) can be mana!ed either by cyclic combined *6+ therapy for establishment of re!ular menses (e.!." )/.), or by I7 !onadotropin therapy (*75Ah/5) for induction of ovulation in cases of anovulatory infertility. b) (%tu%tary macroadenomas) rarely cases with increased intracranial tension or those unresponsive to medical therapy may re$uire trans-sphenoidal sur!ery or 5amma 4nife.

ANA#OMI- S,R%I-A$ -ORRE-#ION:


In some cases sur!ical correction is re$uired to relieve obstruction, or to allow for normal coital function 6* Imper"orate hymen: is easily corrected with sur!ery via a cruciate incision of the hymen. 7* #rans(erse (aginal sept!m will re$uire e:cision. 8* 4a$%nal a$enes%s" can under!o formation of a functional neo-va!ina, with s4in !raftin!. 9* 5onadectomy" is sometimes indicated in patients with testicular feminisation, and those with dys!enetic !onads, in presence of a L chromosome, due to the ris4 of mali!nant transformation (!onadoblastoma). 2uch cases will re$uire lon! life *6+ to improve secondary se:ual characters, and avoid e:cessive bone loss and osteoporosis.

%A$A-#ORRHOEA
(alactorrhoea is the continuous secretion of mil! from the breasts in the absence of recent pregnancy. "t is almost always secondary to hyperprolactinaemia. .rolactin is a polypeptide hormone secreted by the lactotroph cells of the anterior pituitary !land. Its secretion is controlled by hypothalamic prolactin inhibitin! factor (dopamine) in contrast to all other anterior pituitary hormones which are controlled by hypothalamic stimulatin! factors (5n6*, /+*-6*, +6*, 5*-6*M.) -A,SES O' H&PERPRO$A-#INAEMIA: '. *. (hys%olo$%cal) In some women mil4 may be e:pressed for several months after lactation has stopped. 6ru$ %nduced) 2ome dru!s may cause hyperprolactinaemia with or without !alactorrhoea - .henothia8ine derivatives, reserpine and !an!lion bloc4in! a!ents. - .sychotropic dru!s and tricyclic antidepressants. -. (%tu%tary d%sorders) Pituitary hyperplasia Prolactinomas" (microadenomas and macroadenomas), cause hyperprolactinaemia associated with symptoms and si!ns of increased intracranial tension (headache, visual disturbance, and diminution in the field of vision). .hiari &rommel syndrome" characteri8ed by lactational amenorrhoea associated with uterine super involution (small uterus) persistin! for years after pre!nancy. functional failure of the hypothalamus and the pituitary to return to 12* secretion instead of prolactin is postulated as a cause, however a pituitary tumour will be found sooner or later in '0 % of cases. similar picture (&orbes2 or 3el .astillo2s syndrome) can occur without a precedin! pre!nancy and is then sometimes, but not always, caused by a chromophobe adenoma of the pituitary.

7 4. /.

1hyro%d d%sorders) 5alactorrhoea is described in association with hypothyroidism possibly in association with persistently elevated +2*. 8ther rare causes; for an un4nown reason, !alactorrhea sometimes occurs with pulmonary disease and followin! thoracic operations.

+IA%NOSIS ,levated serum prolactin levels usually correlate with the character of the lesion Iormal serum prolactin levels ran!e from -.K E -K n!Aml .ituitary hyperplasia" levels usually % &0 n!Aml .ituitary adenomas" levels usually % 100 n!Aml

#REA#MEN# 1. -. &. ,:clude pituitary tumour (brain /+ A 76I scans). ,:clude thyroid disease by (+2*-+&-+?), and mana!e accordin!ly. Dru!s used for treatment of hyperprolactinaemia (dopamine a!onists) 4romoergocryptine 0 mg (1-- tablets daily, until restoration of normal levels). lisuride hydrogen maleate 5.0 mg (1-- tablets daily, until restoration of normal levels)

.abergoline 5.6 mg (1A- tablet twice wee4ly for ? wee4s).

PO$&-&S#I- OVAR& S&N+ROME .P-OS/


In 1935 'tein and #eventhal were the first to describe a syndrome of amenorrhea8 hirsutism8 obesity8 in association with infertility in a !roup of patients who also showed cystic changes in their o$aries . 0ater on the condition has been described as the ./)2.

+e"inition o" P-OS


./)2 describes a triad of chronic ano$ulation, with features of hyperandrogenism (hirsutism, increased ovarian andro!en, increased 0*), and ultrasound P%O morphology (described later).

Pre(alence and aetiology:


./)2 may affect up to /7'9: of women in the reproductive a!e ./) alone on can be detected by B2 in almost -'% of otherwise normal females +he e:act aetiolo!y of the syndrome remains unclear. familial bac4!round is su!!ested with a special gene related to its development.

Pathogenesis:
./)2 is characteri8ed by e:cessive ovarian andro!en production, increased 0* levels, low E normal 12* levels, decreased 2*(5, increased insulin resistance leadin! to hyperinsulinaemia a Hyperandrogenaemia" * ,:cess andro!en, converted in fatty tissue into estrone (,1), will result in increased pituitary 0* and suppression of 12* (abnormal 0*A12* ratio). * +onically elevated 0* levels and low-normal 12* levels will result in" arrest of follicular !rowth, creatin! a state of chronic anovulation with secondary amenorrhoea or oli!omenorrhoea. * Increased andro!ens levels produced from theca cells, to!ether with decreased hepatic 2*(5 results in increased free testosterone (+) levels with associated abnormal e:cessive hair !rowth (hirsutism). * ,:cess suprarenal andro!en production as in congenital adrenal hyperplasia (/ *) may lead to secondary polycystic ovary chan!es. b Hyperinsulinaemia" * ./)2 may be associated with peripheral insulin resistance disorder leadin! to hyperinsulinaemia. * *yperinsulinaemia increases the sensitivity of ovarian theca cells to 0* and decrease aromata8e en8yme activity leadin! to over-production of ovarian andro!ens (hyperandro!enaemia). N.B.; * ./)2 patients are at increased ris4 for diabetes mellitus, obesity, and cardiovascular disease. * ./)2 patients are also at increased ris4 of endometrial hyperplasia due to hi!her levels of increased free oestro!en (oestrone ,1, a wee4ly active oestro!en), unopposed by pro!esterone (anovulation) . loss of '%-10% of body wei!ht may help patients to re-establish ovulatory cycles.

+iagnosis o" P-OS


!) 0l%n%cal #resentat%on) - 7enstrual irre!ularities in the form of 0ry amenorrhea or oligomenorrhoea - DB( may occur in cases with associated endometrial hyperplasia B) ;aboratory %n+est%$at%ons) - ,levated 0* levels with normal 12* lead to #$%&'$ ration of 70. - ,levated levels of plasma ,1, androstenedione ( D), and free +. - *yperinsulinaemia due to associated increased insulin resistance 0) 0lass%c ,ltrasound eatures) ()dam2s criteria) - +he ovaries are increased in si8e and volume, showin! small peripherally arran!ed follicles ran!in! from --10 mm in diameter !ivin! it a nec9lace appearance (strin! of pearls) with increased stroma 6) ;a#arosco#%c a##earance) - ,nlar!ed ovaries with thic4 capsule, and absent !yrii due to chronic anovulation (oyster shell ovary)

0r%ter%a or d%a$nos%s o (08S is made by inclusion of at least two of the followin! criteria"
1. 7enstrual irre!ularity si!nifyin! oli!o-or anovulation (amenorrhoea E oli!omenorrhoea) -. Bltrasound characteristic picture of multiple small peripherally arran!ed cysts (strin! of pearls) &. /linical or laboratory evidence of hyperandro!enism (hirsutism, elevated andro!en levels, elevated 0* levels and low-normal 12* levels).

#REA#MEN# O' P-OS (depends on the presenting symptom):


'. <e%$ht reduct%on; in obese females a reduction of '-10% of body wei!ht reduces insulin and andro!en and improves response to therapy, and may by itself re-establish ovulatory cycles. *. Menstrual %rre$ular%t%es) a. b. c. d. /yclic !esta!en therapy for 10 days every cycle, from day 1<--', usually results in a re!ular -K-&0 days cycle (e.!. medro:y pro!esterone acetate 10 m! per day) /ombined )/. (day '--'), will establish re!ular cycles in cases not re$uestin! pre!nancy -edical treatment aims at increasin! 12* and mimic4in! 0* sur!e thus promotin! follicular !rowth and ovulation. /lomiphene citrate, *75A*/5, or recombinant 12* and 0* can be used. )nti diabetic drugs in cases of insulin resistance (e.!. metformin '00 m! t.d.s.). .orticosteroid therapy is used to suppress /+* production and hence the adrenal !land in case of adrenal hyperandro!enism. 'urgical treatment via laparoscopic ovarian drilling (#/3)" aims at decreasin! ovarian andro!en production. *owever, adhesion formation is an unfavourable side effect of sur!ery. nti-andro!ens as cyproterone acetate

-. In ert%l%ty (see induction of ovulation for details).

?. "%rsut%sm) a. b. /osmetic therapy (0aser therapy, depilation or electrolysis).

10

Hirs!tism
+e"initions Hirsutism: is defined as e:cessive !rowth of androgen dependent sexual hair (present on the upper lip, chin, inner thi!hs, limbs, chest, abdomen and pubic trian!le). It arises from the !rowth promotin! effects of andro!en on the hair follicle, an irreversible effect even when andro!en levels fall. Hypertrichosis: is e:cessive !rowth of androgen independent hair in non se:ual areas, such as the forearm and le!s ;irili<ation: is hirsutism associated with other si!ns of hyperandrogenism such as" increased muscle mass, cliterome!aly, temporal baldness, voice deepenin!, and increased libido. It can also be associated with si!ns of defemini8ation as decreased breast si8e and loss of va!inal lubrication.

-lassi"ication M%ld) fine pi!mented hair affectin! the face (incomplete beard), chest, abdomen 3 perineum. Moderate) coarse pi!mented hair affectin! same areas as in mild cases. Se+ere) coarse pi!mented hair affectin! the face (complete beard), tip of nose, ear lobes, chest, abdomen, perineum 3 pro:imal interphalan!eal Coints. -ommon ca!ses o" hirs!tism '. !drenal $land) - .ongenital adrenal hyperplasia (partial or complete -1 hydro:ylase deficiencyM.). - )drenal tumours1 secrete D* , D* 2, and rarely +estosterone. *. 8+ar%an causes) - /varian hyperandrogenism1 as ./)D, hyperthecosis, stromal cell hyperplasia. - )ndrogenic ovarian tumors as sertoli lyedi! cell tumor, adrenal rest tumor, hilar cell tumor, and !onadoblastoma. +hese tumors secrete mainly testosterone and rarely D* . -. M%=ed o+ar%an > adrenal hy#erandro$en%sm) (-9749: o cases) Increase adrenal production of andro!en leads to inhibition of follicular maturation 3 induction of premature atresia and conse$uent increase in the production of ovarian andro!en.

4. (%tu%tary $land) /ushin!Gs syndrome due to increase production of /+*, acrome!aly due to increased production of 5*, hyperprolactinemia" (prolactin stimulates the production of D* 2 by adrenal !land). )verproduction of adrenal andro!en throu!h corticotropin andro!en stimulatin! hormone (/ 2*). Dana8ol is a 1J alpha ethinyl testosterone derivative used in treatment of endometriosis. .ro!esto!en of the 1F nor-testosterone derivative, used in treatment of abnormal uterine bleedin!. ndro!en is sometimes used for treatment of postmenopausal osteoporosis.

:* Androgenic dr!gs:

;* Idiopathic: 7any cases of hirsutism occur due to increased sensitivity of hair follicles to normal female andro!en levels, eiither due to increased receptor activity or due to increased activity of the en8yme ' alpha reductase, which is responsible for conversion of + into D*+ which has a more potent action.

11

In(estigations o" a case o" hirs!tism a Hormonal assays - .lasma + level (nH 0.--0.K n!Aml), levels % - n!Aml su!!est andro!en secretin! tumor. - 1ree + level (nH 1-&% of total +) it is a !ood inde: for andro!enicity. - D* 2, (nH 8655 0655 n!Aml), levels % F000 n!Aml su!!ests adrenal tumour. c )adiologic in$estigations: - /+ or 76I on the pituitary !land. - I=. for adrenal tumor. - bdominal 3 pelvic ultrasono!raphy, for adrenal tumours, ./)2, and virili8in! ovarian tumours. #reatment o" hirs!tism combination of hormonal suppression of hair !rowth and mechanical hair removal offers the most complete and effective treatment for patients with hirsutism. )nce terminal hair has been established withdrawal of andro!en does not affect the established hair pattern. '. &l%m%nat%on o s#ec% %c causes -6emoval of ovarian or adrenal tumours -,limination of dru!s suspected to contribute to the abnormal hair !rowth -+reatment of /ushin! syndrome, thyroid disease, or hyperprolactinaemia *. "a%r remo+al techn%?ues -2havin!, twee8in!, wa:in!, and use of depilatories, are all temporary used at repeated intervals -(leachin! is effective for mild hair !rowth -.ermanent destruction of hair follicle by electrolysis or more recently by laser, !ive promisin! results -. Su##ress%on o andro$en synthes%s -)ral contraceptive pills ()/.) containin! combined low dose oestro!en and pro!estin are effective in increasin! 2*(5, and decreasin! free + levels. .ro!estins may also inhibit '-N reductase activity. -7edro:y-pro!esterone acetate (D7. )" !iven 1'0 m! I7 every & months results in suppression of 12* and 0*, to!ether with increased testosterone clearance from the circulation. -/orticosteroids (de:ametha8one 1-' m!Aday)" induce suppression of adrenal andro!en production in severe cases of I/ *. 0on! term side effects include osteoporosis, diabetes mellitus, and avascular necrosis of the hip. 7ild cases of / * can be mana!ed successfully with )/.. 4. !ndro$en rece#tor bloc@ers -+hese medications inhibit bindin! of D*+ to the andro!en receptor, thus directly inhibitin! hair !rowth. Ohen combined with )/. or pro!estins further benefit may be obtained. -3pironolactone: is an aldosterone anta!onist used fre$uently as a diuretic that also inhibits 'N reductase and variably suppresses ovarian and adrenal synthesis of andro!en. -%ypretorone acetate: is a potent pro!estin and antiandro!en that inhibits 0* and decreases andro!en levels. It is used for 10 days each cycle. &iane ./ is an )/. that uses cypretorone acetate as a pro!estin and is widely used in treatment of hirsutism in females that re$uest contraception. /. 8ther med%cat%ons -0%met%d%ne) it competes with andro!en at the receptor site. Dose# &00m! 6 times daily. -Insul%n sens%t%A%n$ a$ents; 7etformin" is used in patients with hirsutism associated with ./)2, to improve insulin sensitivity, thus decreasin! hyperinsulinaemia and andro!en levels.

1-

Key Points in Amenorrhoea 8. 0. 3. ;. 6. <. ?. @. A. Primary amenorrhea may occur either due to outflow tract disorders9 chromosomal abnormalities9 gonadal or -ullerian agenesis9 and central hypothalamic disorders. Physical examination for the development of 0ry sexual characters9 integrity of external genitalia9 presence of the uterus and gonads by :' and hormonal assays are the !ey points for proper diagnosis. "n the absence of both uterus and breasts9 !aryotype usually reveals ;<X= pattern "n absence of uterus and presence of breasts9 !aryotype will differentiate between -ullerian agenesis and testicular femini>ation. Pregnancy is the commonest cause of 0ry amenorrhea. /ther causes include hyperprolactinaemia9 chronic anovulation9 premature ovarian failure9 'heehan syndrome and )sherman syndrome. Pituitary &'$ and #$ levels will differentiate between hypergonadotrophic and hypogonadotrophic amenorrhea9 while prolactin levels will exclude hyperprolactinaemia. Treatment of amenorrhoea is specific to the cause9 and may include hormone replacement therapy9 induction of ovulation9 treatment of hyperprlactinaemia9 correction of thyroid and adrenal disorders. 'urgical treatment includes correction of outflow tract disorders9 creation of neo vagina9 and +onadectomy in cases with = chromosome disorders. $yperprolactinaemia is a common cause of 0ry amenorrhoea treated medically by dopamine agonists

85. P./' is the commonest cause of 0ry amenorrhoea diagnosed by combination of clinical laboratory and :' criteria. "ts treatment depends upon the clinical presentation whether infertility9 hirsutism9 or menstrual disorders. 88. $irsutism may be idiopathic in many cases. "t may be one of the androgenic manifestations of P./'9 or otherwise secondary to endocrine disorders in the pituitary9 thyroid9 or adrenal glands 80. Treatment of hirsutism includes, elimination of the cause9 suppression of androgen synthesis9 and use of androgen receptor bloc!ers.

1&