Hormones and InfertilityHormones and Infertility

By SP Rugera (Senior Lecturer)By SP Rugera (Senior Lecturer)MBARARA UNIVERSITYMBARARA UNIVERSITY

Date: 06/05/2014Date: 06/05/2014

REFERENCESREFERENCES INFERTILITY AND HORMONESINFERTILITY AND HORMONES: :

http://www.fertility.com/international/ accessed 03.05.2014 accessed 03.05.2014

TIETZ TEXTBOOK OF CLINICAL CHEMISTRY: Edited by Carl TIETZ TEXTBOOK OF CLINICAL CHEMISTRY: Edited by Carl Burtis, Edward R. Ashwood Third Edition Pages 1620-1627Burtis, Edward R. Ashwood Third Edition Pages 1620-1627

A MANUAL OF LABORATORY and DIAGNOSTIC TESTS by A MANUAL OF LABORATORY and DIAGNOSTIC TESTS by Frances Fischbach Pages 358-383Frances Fischbach Pages 358-383

CLINICAL DIAGNOSIS AND MANAGEMENT BY LABORATORY CLINICAL DIAGNOSIS AND MANAGEMENT BY LABORATORY METHODS: Edited by John Bernard Henry 20METHODS: Edited by John Bernard Henry 20thth Edition Pages Edition Pages 304-332 304-332

INTRODUCTIONINTRODUCTION According to the World Health Organisation According to the World Health Organisation

(WHO), about 15% of couples of childbearing age (WHO), about 15% of couples of childbearing age seek medical help for infertilityseek medical help for infertility

The problem can stem from both female and The problem can stem from both female and male issues. Generally speaking, the source of male issues. Generally speaking, the source of infertility is:infertility is: Exclusively with the female in about 30 - 40% of cases.Exclusively with the female in about 30 - 40% of cases. Exclusively with the male in about 10 - 30% of cases.Exclusively with the male in about 10 - 30% of cases. A combination of both partners having detectable A combination of both partners having detectable

abnormalities in 15 - 30% of cases.abnormalities in 15 - 30% of cases.

Percentage incidence of Percentage incidence of causes of infertilitycauses of infertility

DEFINITION/OCCURENCEDEFINITION/OCCURENCE Absence of pregnancy - one year of uninterrupted Absence of pregnancy - one year of uninterrupted

sex (NO contraceptives) sex (NO contraceptives)

Primary:Primary: NNo previous successful pregnancy o previous successful pregnancy (Now unable to conceive)(Now unable to conceive)

Secondary:Secondary: Previous successful pregnancy (Now Previous successful pregnancy (Now unable to conceive)unable to conceive)

Occurrence: Occurrence: 50% of infertility of male origin50% of infertility of male origin

INTERLOCKING PLAYERSINTERLOCKING PLAYERSThe following are important players:The following are important players:

Woman's ovulatory cycle Woman's ovulatory cycle

Production of sperm in the male Production of sperm in the male

Hormones (gonadotropins) = affect Hormones (gonadotropins) = affect the ovaries and the testes the ovaries and the testes

HORMONE PRODUCTION HORMONE PRODUCTION SITESSITES

REPRODUCTION REPRODUCTION GONADOTROPINSGONADOTROPINS

human follicle stimulating hormone (hFSH) – human follicle stimulating hormone (hFSH) – (pituitary gland)(pituitary gland)

human luteinizing hormone (hLH) – (pituitary human luteinizing hormone (hLH) – (pituitary gland) gland)

-Both under secretion control gonadotropin--Both under secretion control gonadotropin-releasing hormone (GnRH) – (hypothalamus).releasing hormone (GnRH) – (hypothalamus).

human chorionic gonadotropin (hCG) - human chorionic gonadotropin (hCG) - placenta (maintains pregnancy after placenta (maintains pregnancy after implantation)implantation)

THE FEMALE AND MENSTRUAL THE FEMALE AND MENSTRUAL CYCLESCYCLES

FEMALE SEXUAL FEMALE SEXUAL ORGANORGAN

FEMALE SEXUAL ORGANSFEMALE SEXUAL ORGANS

THE FEMALE AND MENSTRUAL THE FEMALE AND MENSTRUAL CYCLES CYCLES continuedcontinued

Menstrual cycle occurs in three phases:Menstrual cycle occurs in three phases:

Follicular phase:Follicular phase: Days 1 to 13. Days 1 to 13.

Ovulatory phase:Ovulatory phase: Around day 14. Around day 14.

Luteal phase:Luteal phase: Days 15 to 28.  Days 15 to 28. 

THE FEMALE AND MENSTRUAL THE FEMALE AND MENSTRUAL CYCLES CYCLES continuedcontinued

The cycle controlled by hormones:The cycle controlled by hormones:   Follicle stimulating hormone (FSH)Follicle stimulating hormone (FSH)

Luteinizing hormone (LH)Luteinizing hormone (LH)

OestrogenOestrogen

Progesterone     Progesterone     

THE FEMALE AND MENSTRUAL THE FEMALE AND MENSTRUAL CYCLES CYCLES continuedcontinued

FEMALE INFERTILITYFEMALE INFERTILITY

The following factors contribute:The following factors contribute:ovarian (hormonal)ovarian (hormonal)tubal tubal cervicalcervicaluterineuterinepsychosocialpsychosocial immunologicimmunologic

FACTORS FACTORS continuedcontinued

Factor’s contribution:Factor’s contribution:Ovulatory - 30% of all cases of Ovulatory - 30% of all cases of

infertilityinfertilitypelvic - 50% pelvic - 50% immunologic - 5%.immunologic - 5%.Others - 15%Others - 15%

ENDOMETRIOSIS (causes ENDOMETRIOSIS (causes mechanical obstruction) mechanical obstruction)

OVULATORY DYSFUNCTIONOVULATORY DYSFUNCTION Can develop regard less of normal menses Can develop regard less of normal menses

- dysfunction difficult to diagnose. - dysfunction difficult to diagnose. Complicated by many metabolic diseases Complicated by many metabolic diseases

that affect ovulatory function. that affect ovulatory function.

There are also diseases that tend to There are also diseases that tend to increase androgen levels - include increase androgen levels - include Thyroid, liver disease as well as obesity.Thyroid, liver disease as well as obesity.

HYPOGONADISM HYPOGONADISM Hypogonadism (decreased functional Hypogonadism (decreased functional

activity of the gonads) - also cause activity of the gonads) - also cause infertility in the femaleinfertility in the female

Either Hypergonadotropic or Either Hypergonadotropic or hypogonadotropic (increased or hypogonadotropic (increased or reduced gonadotropins)reduced gonadotropins)

REFERENCE VALUESREFERENCE VALUEShhCG - absent in serum or urine – not CG - absent in serum or urine – not

pregnantpregnantFSH Female FSH Female

FollicularFollicular 1.68-15 IU/L1.68-15 IU/LOvulatory peakOvulatory peak 21.9 – 56.621.9 – 56.6LutealLuteal 0.61-16.30.61-16.3PostmenopausePostmenopause 14.2-52.314.2-52.3

MaleMale 1.24-7.81.24-7.8

REFERENCE VALUES REFERENCE VALUES continuedcontinued

LHLHFollicularFollicular 1.37-9.9 IU/L1.37-9.9 IU/LOvulatory peakOvulatory peak 6.17 – 17.26.17 – 17.2LutealLuteal 1.09-9.21.09-9.2PostmenopausePostmenopause 19.3-100.619.3-100.6

MaleMale 1.42-15.41.42-15.4

REFERENCE VALUES REFERENCE VALUES continuedcontinued

ProlactinProlactin Non pregnant - 0-23ng/mLNon pregnant - 0-23ng/mL

Pregnant – 34-386 ng/mLPregnant – 34-386 ng/mL

Men – 0-20 ng/mLMen – 0-20 ng/mL

Children 3.2-20 ng/mLChildren 3.2-20 ng/mL

REFERENCE VALUES REFERENCE VALUES continuedcontinued

TestosteroneTestosteroneMen – 270-1070 ng/mLMen – 270-1070 ng/mLChildren – 0-20 ng/mLChildren – 0-20 ng/mLWomen – 15-70 ng/mLWomen – 15-70 ng/mL

REFERENCE VALUES REFERENCE VALUES continuedcontinued

ProgesteroneProgesterone

Men – Less than 1.0ng/mLMen – Less than 1.0ng/mL WomenWomen

PrepubertalPrepubertal 0.1-0.3 ng/mL0.1-0.3 ng/mL FollicularFollicular 0.1-0.7 ng/mL0.1-0.7 ng/mL LutealLuteal 2-25 ng/mL2-25 ng/mL First timesterFirst timester 10-44 ng/mL10-44 ng/mL Second Second 19.5-82.5 ng/mL19.5-82.5 ng/mL ThirdThird 65-290 ng/mL65-290 ng/mL

Hypergonadotropic Hypergonadotropic hypogonadismhypogonadism

Causes of hypergonatropic hypogonadism:Causes of hypergonatropic hypogonadism:

premature ovarian failurepremature ovarian failure

gonadal dysgenesis (Turner syndrome and its gonadal dysgenesis (Turner syndrome and its variants)variants)

resistant ovary syndromeresistant ovary syndrome

menopause and menopause and

luteal phase deficiency. luteal phase deficiency.

Hypogonatropic Hypogonatropic hypogonadismhypogonadism

Causes of hypogonatropic Causes of hypogonatropic hypogonadism:hypogonadism:

pituitary or hypothalamic pituitary or hypothalamic insufficiencyinsufficiency

hyperprolactinaemia.hyperprolactinaemia.

LABORATORY ASSESSMENT LABORATORY ASSESSMENT OF FEMALE INFERTILITYOF FEMALE INFERTILITY

Initial history + physical examination, Initial history + physical examination, menstrual history importantmenstrual history important

Ovulation:Ovulation:

Infertile despite clinically normal menstrual Infertile despite clinically normal menstrual cycles, or have amenorrhoea or oligonorrhoea.cycles, or have amenorrhoea or oligonorrhoea.

Even if cycle regular: determine whether Even if cycle regular: determine whether

ovulation occurring + if luteal development is ovulation occurring + if luteal development is normal.normal.

Ovulation evaluationOvulation evaluation ProgestoneProgestone level is the primary assay level is the primary assay

Immediately after ovulation, progesterone levels Immediately after ovulation, progesterone levels rise reaching a maximum after 5 days. rise reaching a maximum after 5 days.

If ovulation does not occur, the expected rise is If ovulation does not occur, the expected rise is lower than normallower than normal

Mid luteal phase levels are indicators:Mid luteal phase levels are indicators:

>10ng/mL - Normal ovulation>10ng/mL - Normal ovulation <10ng/mL - Anovulation, inadequate luteal phase <10ng/mL - Anovulation, inadequate luteal phase

progesterone production or inappropriate timing progesterone production or inappropriate timing of sample collection.of sample collection.

Ovulation evaluation Ovulation evaluation continuedcontinued

Monitoring of basal body temperatureMonitoring of basal body temperature: :

Ovulation produces a rapid rise in body Ovulation produces a rapid rise in body temperature of 0.5temperature of 0.5ooF (persist through luteal F (persist through luteal phase) - Temperature chartsphase) - Temperature charts

This is not helpful as it is retrospective (you This is not helpful as it is retrospective (you

cannot use it to time the period of cannot use it to time the period of intercourse that yields fertilization)intercourse that yields fertilization)

Ovulation evaluation Ovulation evaluation continuedcontinued

Luteinising Hormone surgeLuteinising Hormone surge: :

Luteinising hormone physiologically Luteinising hormone physiologically appears in urine after a surge (24 – appears in urine after a surge (24 – 36hrs before ovulation). 36hrs before ovulation).

Useful in timing intercourse for Useful in timing intercourse for possible fertilization. possible fertilization.

However does not confirm presence of However does not confirm presence of ovulation or the cause of anovulation.ovulation or the cause of anovulation.

Ovulation evaluation Ovulation evaluation continuedcontinued

LH KITS TO TIME OVULATIONLH KITS TO TIME OVULATION Physiological surge led to development of LH Physiological surge led to development of LH

hormone kits – ACCURATE TIMING OF OVULATION hormone kits – ACCURATE TIMING OF OVULATION Uses “dipstick” with two site double monoclonal Uses “dipstick” with two site double monoclonal

enzyme linked antibody to detect presence of LH enzyme linked antibody to detect presence of LH in urine in urine

A positive test indicates LH surge is occurring. A positive test indicates LH surge is occurring. Predicts ovulation APPROX. 70% of cases. Predicts ovulation APPROX. 70% of cases.

Some studies show a 92% positive predictive Some studies show a 92% positive predictive value with LH home kits for ovulation to occur value with LH home kits for ovulation to occur within 48 hours of a positive urine LH screen.within 48 hours of a positive urine LH screen.

Evaluation of endocrine Evaluation of endocrine parameterparameter

Hypergonadotropic hypogonadism Hypergonadotropic hypogonadism Repeatedly elevated basal FSH trends (> 30 I U/L) Repeatedly elevated basal FSH trends (> 30 I U/L)

or a single elevation of >40 Iu/L indicates primary or a single elevation of >40 Iu/L indicates primary ovarian failureovarian failure

Estradiol levels of < 20 Iu/L (hypoestrogenic) are Estradiol levels of < 20 Iu/L (hypoestrogenic) are evident in hypergonadotropic hypogonadismevident in hypergonadotropic hypogonadism

HyperprolactinaemiaHyperprolactinaemia

Luteal phase deficiency is diagnosed when period Luteal phase deficiency is diagnosed when period between ovulation and menses is 10 days or less.between ovulation and menses is 10 days or less.

Evaluation of endocrine Evaluation of endocrine parameter parameter continuedcontinued

Hypogonadotropic hypogonadismHypogonadotropic hypogonadism

Estradiol levels <40 pg/mLEstradiol levels <40 pg/mL

Decreased LH levels (< 10 Iu/L)Decreased LH levels (< 10 Iu/L)

Decreased FSH levels (< 10 Iu/L)Decreased FSH levels (< 10 Iu/L)

HypothyroidismHypothyroidism

MALE INFERTILITYMALE INFERTILITYHypogonadism - results into lowered Hypogonadism - results into lowered

testosterone levels - affects sperm testosterone levels - affects sperm development (infertility) development (infertility)

Infertility can be due either Infertility can be due either hypogonatropic or hypogonatropic or hypergonadotropic hypogonadism.hypergonadotropic hypogonadism.

Factors leading to male Factors leading to male InfertilityInfertility

These include Endocrine as well as non These include Endocrine as well as non endocrineendocrine : :

EndocrineEndocrine

◊◊Hypothalmic dysfunctionHypothalmic dysfunction: (majorly Kallmann’s syndrome) : (majorly Kallmann’s syndrome) due to hypogonatropic hypogonadism whose causes due to hypogonatropic hypogonadism whose causes include:include:- GnRH deficiency and- GnRH deficiency and-Hyper-prolactinaemia. -Hyper-prolactinaemia. Deficiency of GnRH in hypothalamus causes Kallmann’s Deficiency of GnRH in hypothalamus causes Kallmann’s syndrome. syndrome.

Hyperprolactaemia impairs GnRH release - impotence. Drugs that Hyperprolactaemia impairs GnRH release - impotence. Drugs that increase proclactin e.g. antihypertensive drugs also cause thisincrease proclactin e.g. antihypertensive drugs also cause this

◊ ◊ Pituitary dysfunctionPituitary dysfunction: : Resulting majorly from surgery, radiation or Resulting majorly from surgery, radiation or adenomas.adenomas.

Factors leading to male Infertility Factors leading to male Infertility continuedcontinued

Non direct endocrine:Non direct endocrine:

◊◊ Antibodies to spermsAntibodies to sperms: : Antibodies decrease motility; Antibodies decrease motility; cause agglutination - sperm failure.cause agglutination - sperm failure.

◊◊ Others: Others: ▪ ▪ Exogenous androgens, Exogenous androgens, ▪ ▪ thyroid disorders, thyroid disorders, ▪ ▪ adrenal hyperplasia and testicular failure adrenal hyperplasia and testicular failure anatomic anatomic ▪ ▪ abnormal spermatogenesis abnormal spermatogenesis ▪ ▪ psychosocial problems psychosocial problems ▪▪Obesity in the infertility male (Gynaecomastia) - Obesity in the infertility male (Gynaecomastia) - sign of high concentration of oestrogen or most sign of high concentration of oestrogen or most likely testicular feminisation syndrome.likely testicular feminisation syndrome.

LABORATORY ASSESSMENT LABORATORY ASSESSMENT OF MALE INFERTILITYOF MALE INFERTILITY

May detect early hormonal deficiency or distinguish May detect early hormonal deficiency or distinguish between testicular and pituitary causes.between testicular and pituitary causes.

Initial evaluation - detailed history of patient Initial evaluation - detailed history of patient targeting reproductive organs for evidence of proper targeting reproductive organs for evidence of proper androgenisation (include medication/systemic illness androgenisation (include medication/systemic illness or potential toxin exposure) or potential toxin exposure)

The laboratory evaluation has three major aspects: The laboratory evaluation has three major aspects: SEMEN ANALYSIS/ENDOCRINE SEMEN ANALYSIS/ENDOCRINE PARAMETERS/IMMUNOLOGICAL PARAMETERSPARAMETERS/IMMUNOLOGICAL PARAMETERS

Semen analysisSemen analysis ejaculate volume, pH, motility and motility direction ejaculate volume, pH, motility and motility direction ParameterParameter ValueValue Ejaculate volumeEjaculate volume > 2 mL> 2 mL Sperm DensitySperm Density > 20 million/mL> 20 million/mL Total sperm countTotal sperm count > 40 million per ejaculate> 40 million per ejaculate MotilityMotility > 50% forward (60 min > 50% forward (60 min

of ejaculation)of ejaculation) MorphologyMorphology > 30% normal> 30% normal PHPH 7.2 – 87.2 – 8 Colour Colour Grey white yellowGrey white yellow LiquefactionLiquefaction With in 40 minWith in 40 min Acid phoshataseAcid phoshatase 100-300100-300μμg/mL g/mL Others (Fructose, Citric acid, Inositol, Zinc, Magnesium, Others (Fructose, Citric acid, Inositol, Zinc, Magnesium,

Prostaglandins, glycerophosphorylcholine, Carnitine, Prostaglandins, glycerophosphorylcholine, Carnitine, Glucosidase)Glucosidase)

Endocrine parametersEndocrine parametersEndocrine parametersEndocrine parameters

Serum testosteroneSerum testosterone IfIf male shows male shows evidence of deficient dev. of secondary evidence of deficient dev. of secondary sex characteristics sex characteristics

Subject to Subject to HcgHcg stimulation (5000 IU stimulation (5000 IU Hcg)Hcg)Measure testosterone 48-96hrs laterMeasure testosterone 48-96hrs laterDecreased testerone (infertilty)Decreased testerone (infertilty)

Endocrine parameters Endocrine parameters continuedcontinued

Hypergonadtropic hypogonadismHypergonadtropic hypogonadism

FSH FSH -Should be measured in males with sperm counts -Should be measured in males with sperm counts

less than 5 – 10 million/mL. less than 5 – 10 million/mL.

-Elevated levels of FSH (sertoli cell dysfunction, -Elevated levels of FSH (sertoli cell dysfunction, azoospermia, primary germinal cell failure or azoospermia, primary germinal cell failure or genetic conditions e.g Klinefelters syndrome) genetic conditions e.g Klinefelters syndrome)

-Elevated FSH and LH with decreased -Elevated FSH and LH with decreased testosterone and oligospermia indicate primary testosterone and oligospermia indicate primary testicular failure (andropause)testicular failure (andropause)

Endocrine parameters Endocrine parameters continuedcontinued

Exogenous GnRH administrationExogenous GnRH administration Administered GnRH - distinguishes Administered GnRH - distinguishes

between gonadal insufficiency between gonadal insufficiency (pituitary failure or hypothalamic (pituitary failure or hypothalamic failure)failure)

FSH levels are measured at 15, 30, 90 FSH levels are measured at 15, 30, 90 and 120 minutes after administration. and 120 minutes after administration.

Endocrine parameters Endocrine parameters continuedcontinued

Interpretation of results:Interpretation of results: No rise in FSH and LHNo rise in FSH and LH indicates indicates Pituitary failure.Pituitary failure.

Increase < Increase < 2times FSH levels from initial value2times FSH levels from initial value and /or and /or maximum level does not exceed 3mIu/mL maximum level does not exceed 3mIu/mL indicates indicates relative relative pituitary insuffiency.pituitary insuffiency.

Increase Increase FSH levels to <3times the initial valueFSH levels to <3times the initial value and the and the maximum does not exceed 9mIu/mL maximum does not exceed 9mIu/mL indicates indicates occlusion of occlusion of sperm conveying structures (azoospermic patients) – there is sperm conveying structures (azoospermic patients) – there is need for a testicular biopsy for confirmation of diagnosis.need for a testicular biopsy for confirmation of diagnosis.

Increase FSH - Increase FSH - >3times the basal levels>3times the basal levels and/or maximum and/or maximum greater than 9 mIu/mL greater than 9 mIu/mL indicates indicates exaggerated GnRH exaggerated GnRH response (masked hypergonadotropic hyponadism or in response (masked hypergonadotropic hyponadism or in adequate GnRH pulsability by the hypothalamus)adequate GnRH pulsability by the hypothalamus)

Endocrine parameters Endocrine parameters continuedcontinued

Immunologic parametersImmunologic parameters Antisperm antibodies detected in the Antisperm antibodies detected in the

techniques (agglutination, ELISAs RIAs, and techniques (agglutination, ELISAs RIAs, and immunoflourescent) immunoflourescent)

Antibodies on a carrier recognize any human Antibodies on a carrier recognize any human immunoglobin (antisperm antibodies) in the immunoglobin (antisperm antibodies) in the serum. serum.

High percentage - cause is antisperm High percentage - cause is antisperm antibodies.antibodies.

SPECIAL HORMONAL OCURRENCES IN SPECIAL HORMONAL OCURRENCES IN THE FEMALE CONDITIONS OTHER THAN THE FEMALE CONDITIONS OTHER THAN

INFERTILITYINFERTILITYAMMENORHOEAAMMENORHOEAAbsence of menstrual bleeding in a Absence of menstrual bleeding in a

normal ovulatory menstrual cycle normal ovulatory menstrual cycle Normal bleeding – every after 28days Normal bleeding – every after 28days

Varies between 25 – 30 days in Varies between 25 – 30 days in

healthy femaleshealthy females

AMMENORHOEAAMMENORHOEA

Primary ammenorrhoeaPrimary ammenorrhoea - NO spontaneous - NO spontaneous periodic menstruation by the age of 16 years periodic menstruation by the age of 16 years (with/out female secondary sexual xteristics)(with/out female secondary sexual xteristics)

Secondary ammenorrhoea Secondary ammenorrhoea refers to refers to absence of periodic menstruation for absence of periodic menstruation for at least 6 months in a female - previously at least 6 months in a female - previously

experienced menses experienced menses 12 months in females with a history of 12 months in females with a history of

oligomenorrhoea or infrequent menstruations oligomenorrhoea or infrequent menstruations (less than 9 times in a year)(less than 9 times in a year)

AAMMENORHOEAMMENORHOEA continuedcontinued

Cause of ammenorrhoea (Cause of ammenorrhoea (usually overlap)usually overlap):: Pregnancy( chorionic gonadotrophin antibodies in urine - pregnancy test)Pregnancy( chorionic gonadotrophin antibodies in urine - pregnancy test)

Lower tract defects (viginal aplasia, imperfolate hymen, congenital, vaginal Lower tract defects (viginal aplasia, imperfolate hymen, congenital, vaginal atresia), uterine disorders, ovarian disorders (various syndromes including atresia), uterine disorders, ovarian disorders (various syndromes including Turners, testicular fertilization, polysystic ovary), adrenal disorders Turners, testicular fertilization, polysystic ovary), adrenal disorders (congenital adrenal hypoplasma) hypothyroidism, pituitary- hypothalam ic (congenital adrenal hypoplasma) hypothyroidism, pituitary- hypothalam ic disorders (hypopitutation, Kallmann’s syndrome)disorders (hypopitutation, Kallmann’s syndrome)

Secondary ammenorrhoea include: uterine disorders (post traumatic, Secondary ammenorrhoea include: uterine disorders (post traumatic, progestational agents) ovarian disorders (polycystic ovary syndrome, progestational agents) ovarian disorders (polycystic ovary syndrome, ovarian tumors, premature ovarian failure) adrenal hyperplasia, cushings ovarian tumors, premature ovarian failure) adrenal hyperplasia, cushings syndrome, hypo/hyperthyroidism, tumors of the hypothalamus, stress e.t.c.syndrome, hypo/hyperthyroidism, tumors of the hypothalamus, stress e.t.c.

Hyperprolactinaemia is an important cause of ammenorrhoea. High plasma Hyperprolactinaemia is an important cause of ammenorrhoea. High plasma prolactin levels inhibit the normal pulsatile release of GnRH and inhibit prolactin levels inhibit the normal pulsatile release of GnRH and inhibit gonadal steroid hormone synthesis directly. This causes low gonadotrophin gonadal steroid hormone synthesis directly. This causes low gonadotrophin and oestrogen levels and symptoms of oestrogen deficiency.and oestrogen levels and symptoms of oestrogen deficiency.

NOTE: INTEPRETE hyperprolactinaemia with caution. Samples should be NOTE: INTEPRETE hyperprolactinaemia with caution. Samples should be taken 2 – 3 hours after waking up. Even minor stresses e.g. during taken 2 – 3 hours after waking up. Even minor stresses e.g. during venepuncture or drugs e.g. methyldopa and patients on estrogen seem to venepuncture or drugs e.g. methyldopa and patients on estrogen seem to affect it (increase)affect it (increase)

CROSS CUTTING SPECIAL CASES: CROSS CUTTING SPECIAL CASES: HIRSUTISM AND VIRILISATION HIRSUTISM AND VIRILISATION

HIRSUTISM HIRSUTISM Excessive growth of terminal hair on girls, Excessive growth of terminal hair on girls,

boys and women in a distribution similar boys and women in a distribution similar to that occurring in post pubertal mento that occurring in post pubertal men

True hirsutism occurs in women and True hirsutism occurs in women and evidenced by increase in androgens. evidenced by increase in androgens. However idiopathic hirsutism occurs at a However idiopathic hirsutism occurs at a rate of 50% in all hirsute women. In such rate of 50% in all hirsute women. In such cases normal physical and laboratory cases normal physical and laboratory findings are evident findings are evident

HIRSUTISMHIRSUTISM continuedcontinued

Testosterone is the most important hormone. In normal Testosterone is the most important hormone. In normal women, about half the plasma testosterone comes from the women, about half the plasma testosterone comes from the ovary, both by direct secretion and by peripheral ovary, both by direct secretion and by peripheral conversion of androstenedione. The rest is derived from conversion of androstenedione. The rest is derived from peripheral conversion of adrenal androstenedione and peripheral conversion of adrenal androstenedione and dehydroepiandrosterone (DHEA)dehydroepiandrosterone (DHEA)

Evaluation of both disorders is through estimation of both Evaluation of both disorders is through estimation of both testosterone and DHEA. High DHEA-S suggest the testosterone and DHEA. High DHEA-S suggest the androgens are of adrenal origin whereas high testosterone androgens are of adrenal origin whereas high testosterone suggests either an adrenal or ovarian source (but majorly suggests either an adrenal or ovarian source (but majorly ovarian).ovarian).

In hirsutism, plasma LH is increased with a high LH to FSH In hirsutism, plasma LH is increased with a high LH to FSH of usually greater than 3:1. Plasma testosterone levels are of usually greater than 3:1. Plasma testosterone levels are high. This is sometimes accompanied by raised levels of high. This is sometimes accompanied by raised levels of prolactin.prolactin.

VIRILISMVIRILISM Virilism is a serious case than hirsutism Virilism is a serious case than hirsutism Also associated with increased androgen levelsAlso associated with increased androgen levels Identified by Identified by

enlargement clitoris, enlargement clitoris, Increased hair growth of male distributionIncreased hair growth of male distribution deepening of voice and breast atrophy deepening of voice and breast atrophy

Main causes - ovarian tumors which secrete Main causes - ovarian tumors which secrete androgens mainly testosterone and adrenocortical androgens mainly testosterone and adrenocortical pathology especially tumors e.g pituitary dependent pathology especially tumors e.g pituitary dependent cushings syndrome (although rarely). There is a rise cushings syndrome (although rarely). There is a rise in DHEASin DHEAS