Dr. ASMAA GYNECOLOGY lec5
Primary amenorrhoeaThe student at the end of this lectureshould be able to :Define primary amenorrhoea.Classify the causes of primaryamenorrhoea.Understand the changes of puberty.Exclude anatomical abnormality inpatients with normal secondary sexualcharacteristics.Primary amenorrhoea :is defined as absence of spontaneous menstruation by 16 years of age in the presence of normal secondary sexual characteristics OR by 14 years of age when there is absence of secondary sexual characteristics (2 years of thelarche) menstruation is not an event but part of the sexual development at the time of puberty ,it occurs at any time between the 10-18 years old .NORMAL PUBERTY:Puberty is the time when one becomes functionally able to reproduce ,including both physical and psychological development.
There is 5 changes (secondary sexual characteristics)these are the :-breast growth. -pubic hair growth-axillary hair growth-growth spurt-onset of menstruationlater on ovulation become established.These changes occurs as a result of endocrine changes . During childhood gonadotrophin levels are low both in term of pulse frequencyand amplitude ,then establishment of the mature hypothalamus and GNRH release leads to a normal endocrine environment. Oestradiol start to rise from the developing ovarian follicles, this oestrogen leads to econdary sexual development of the breast and establishment of menstruation. The secretion of androgen, (DHEA) and (DHEAS) begins from the age of 6 years prime the development of pubic and axillaryhair growth.
Clinical classification of primary amenorrhea:Primary amenorrhea with sexual infantilism.Primary amenorrhea with breastdevelopment and mullerian anomalies.Ammenorrhea /oligomenorrhea with breastdevelopment and normal mullerian system.
1.Primary ammenorrhea with sexual infantilism Hypogonadotrophic causes (low FSH)(LH is low)(oestrogen low)-Failure of GnRH secretion from the hypothalamus.-Failure of FSH secretion from the anterior pituitary. It may result from serious causes as CNS tumors ,kallman syndrome ,prolactin secretin tumor or general process of pituitary failure MRI,CT is adviced for diagnosisof tumor lesion and in addition of FSH measurement we require TSH,GH,ACTH measurement Apparent hypogonadotrophic hypogonadism may actually represent constitutionally delayed puberty due to undefined hereditary factors,there is commonly a history of late puberty in family members acquired causes of hypogonadotrophichypogonadism:weight loss/ anorexia.Exercisestresshyperprolactinaemia17%of body weight is fat required for initiation of menarche, and 20% is required to maintain menses. The stress increase the level of circulatingEndorphins can reduce the GnRH production by the hypothalamus
Hypergonadotrophic hypogonadisim :causes (High FSH.LH) with low oestrogen Result from congenital or acquired absence of ovarianfollicles, causes includes: Gonadal agenesis/ dysgenesis ,including turner syndrome(45X0)and pure gonadal dysgenesis(46XX,46XY),and mosaicism. Most patient of this group will have no secondary sexual characteristics occasionally patients with mosaicisim or turner syndrome will have sufficient ovarian follicular activity and secrete oestrogen to cause breast development,menstruation,ovulation and rarely even pregnancy . In all patients Karyotype is required to exclude y chromosome as there is risk of development of a gonadoblastoma: a benign germ cell tumor of the gonads ,enentually dysgerminoma a malignant germ cell tumor.
17-hydroxylase(p450c17) deficiencyThere is low sex steroid(oestrogen and androgen) there is hypertension and hypokalemia due to mineralocorticoid excess. (excess aldosterone)
2.primary amenorrhoea with breast development and mullerian abnormality: Patient in this group has 2 categories:• Complete androgen insensitivity syndromeAIS.• Mullerien dysgenesis or agenesis.Differentiation between them is bymeasurement of serum testosterone leveland by determination of karyotype.
Androgen insensitivity syndrome:There is defect in androgen receptor,their karyotype is 46XY and they demonstrate normal level of testosterone although on the lower side of normal,they may also have mildly elevated FSH and LH level becausethe testes are located in the abdominal wall cavity,with greater temperature which is not allowing for normal male hormonal secretion.Breast development is caused by small oestrogen produced by testes and by conversion of androgen to oestrogen in the liver and else where.The testes secrete normal amount of AMH so there is no uterus ,only a small vaginal dimple.
Treatment:gonadal resection to avoidneoplasia once puberty is complete.Creation of neovagina.Psychological counseling.
Mullerian dysgenesis or agenesis:patient with primary amenorrhoea,breast development and 46XXkaryotype have level of testosterone appropriate for females, amenorrhea occurs when the defect cause obstruction of the vaginalcanal like Imperforate hymen transverse vaginal septum absent vagina and functioning uterus absent vagina and non-functioning uterus
Heterosexual development:Congenital adrenal hyperplasiaAndrogen secreting tumors5 alpha reductase deficiencyTrue hermaphroiteAbsent mullerian inhibitor
Evaluation and management of primary amenorrhoeaMost of condition are rare and constitutional delay is the most common diagnosis ,because rest of diagnosis have serious implications diagnosis of constitutional delay should only be made when all other syndrome have been excluded .In constitutional delay the female have normal secondary sexual characteristics , no anatomical abnormality no endocrine abnormality only they have immature pulsatile release of the GnRH. They will eventually menstruate spontaneously as the maturation processproceeds
If there is normal secondary sexual characteristics,checkfor anatomical abnormality:if the uterus is present , then check forout flow tract Obstruction by: examinationUSMRI or CT scanningTreatment is by pelvic reconstructionsurgery.If the uterus is absent check the karyotype:If 46XX, Rokitansky syndrome is themost likely diagnosis.If 46XY, Xy female is the likely diagnosiswhich require surgical removal of thegonads as the malignant potential is 30% inthese patients
IF the anatomy is normal checkthe gonadotrophin and prolactin:If LH:FSH ratio is elevated PCOSIf PRL prolactinomaTreatment is by bromocriptine or surgery if gonadotrophin resistant ovarysyndrome further diagnosis is by ovarianbiopsyif gonadotrophin Indicate constitutionaldelay :reassurance, annual review , mayinduce one cycle by COCPAbout 25%of patients with primaryamenorrhoea with presence of breast andUterus, have :-elevated prolactin serum level.-No galactorrhoea.-radiological abnormality indicate thepresence of pituitary adenomaIf serum prolactin is normal, differentialDiagnosis will include:-PCOS-hypothalamic-pituitarydysfunction(exercise,anorexia)-premature ovarian failure
Absence of secondary sexual characteristics:Measure the gonadotrophin:Low hypogonadotrophic hypogonadismHigh karyotype should be performed:46XX in patients with premature ovarian failure, the resistant ovary syndrome or gonadal agenesis.46XY in 46XY gonadal agenesis or testicular enzymatic failure.In patient with hypogondotrophic hypogonadism treatment directed to:Manage avoidable underlying problems.In isolated GNRH deficiency replacementtherapy (oestrogen and progesterone) toinduce secondary sexual characteristicsdevelopment.These patients can be informed that theyare infertile and ovulation can be inducedby various fertility regimes