HYPERPROLACTINEMIA AND HYPERPROLACTINEMIA AND HYPERANDROGENEMIAHYPERANDROGENEMIA

Prof.Hamonangan HutapeaProf.Hamonangan HutapeaDepartement of Obstetrics and GynecologyDepartement of Obstetrics and Gynecology

Medical FacultyMedical FacultyUniversity of Sumatera UtaraUniversity of Sumatera Utara

Hyperprolactinaemia.Hyperprolactinaemia.

Introduction.Introduction.

Prolactine (PRL) is secreted from the Prolactine (PRL) is secreted from the Anterior Hypophisis.Anterior Hypophisis.

Normal blood level of PRL: 150-500 IU/LNormal blood level of PRL: 150-500 IU/L

or 12.5 – 25 ng/ml.or 12.5 – 25 ng/ml.

During pregnancy,During pregnancy,a tenfold increase in a tenfold increase in serum PRL level.serum PRL level.

There are at least 4 basic molecular types of PRL

hormone circulating in the normal women’s blood :

~ Little Prolactin (native PRL), MW 23 kDa.

~ Big Prolactin, MW ± 50 kDa.

~ Big-big Prolactin, MW ± 150 kDa.

~ Glycosilated Prolactin, MW 25 kDa.

Definition.Definition.

Hyperprolactinaemia is inapropriately Hyperprolactinaemia is inapropriately increased PRL level occuring when the increased PRL level occuring when the woman is non-pregnant, and may cause woman is non-pregnant, and may cause amenorrhoeaamenorrhoea or or galactorrhoeagalactorrhoea or both. or both.

AetiologyAetiology

Pituitary(Pituitary(Hypophisis) tumor; Hypophisis) tumor; 1.Microadenoma :1.Microadenoma :<10mm diameter<10mm diameter 2.Macroadenoma:>10mm diameter.2.Macroadenoma:>10mm diameter.

Hypothyroidism.Hypothyroidism. Primary hypothyroidismPrimary hypothyroidismTRHTRH PRL production.PRL production.

Drugs :Drugs : Dopamine agonist: Dopamine agonist: Phenothiazines,Butyrephenones,Phenothiazines,Butyrephenones, Benzamides,Cimetidine,MethyldopaBenzamides,Cimetidine,Methyldopa Other drugs: antidepressants,opiates,cocaine etcOther drugs: antidepressants,opiates,cocaine etc

IdiopathicIdiopathic

DiagnosisDiagnosis

The diagnosis of hyperprolactinaemia can The diagnosis of hyperprolactinaemia can be made on a single serum measurement.be made on a single serum measurement.

A serum PRL of A serum PRL of ≥≥800 IU/L in the presence 800 IU/L in the presence of oligo-or amenorrhoea, of oligo-or amenorrhoea, pathological pathological significance.significance.

CT-scanning or MRI should be done to CT-scanning or MRI should be done to exclude a hypophysis tumor.exclude a hypophysis tumor.

Mechanism of amenorrhoea.Mechanism of amenorrhoea.

Raised PRL Raised PRL Disturbance of normal Disturbance of normal hypothalamic GnRH releasehypothalamic GnRH releaseLHpulsatility LHpulsatility suppressed suppressed Anovulation/Amenorrhoea. Anovulation/Amenorrhoea.

Control of PRL release:Control of PRL release:

11..TRHTRHHypothalamusHypothalamushypophysishypophysisPRL PRL

22..DopamineDopaminehypophysishypophysisPRLPRL

33..EstrogenEstrogenhypophysishypophysisPRLPRL

44. Breast suckling. Breast sucklingTRH….TRH….PRLPRL

Treatment.Treatment.

1.1. Medicament.Medicament.

a. a. BromocriptineBromocriptine;;2,5mg orally2,5mg orally 2-3 X daily 2-3 X daily with meals.Or by vaginal administration.with meals.Or by vaginal administration.

b. b. QuinagolideQuinagolide.(A new dopamine .(A new dopamine agonist),once a day,tolerated better.agonist),once a day,tolerated better.

c.c. Cabergoline Cabergoline ( a new dopamine ( a new dopamine agonist, long half-life.Administered agonist, long half-life.Administered weekly.weekly.

22. Surgical treatment.. Surgical treatment.

* Trans-sphenoidal surgery is usually * Trans-sphenoidal surgery is usually done to resect both micro-and or done to resect both micro-and or macroadenomas.macroadenomas.

* The results of treatment vary greatly * The results of treatment vary greatly between centres,between centres,±50%±50%

33. Radiotherapy (very rare). Radiotherapy (very rare)

IS THERE ANY QUESTION?IS THERE ANY QUESTION?

Pituitary AdenomaPituitary Adenoma

Pituitary adenomas secreting hormones other Pituitary adenomas secreting hormones other than prolactin may also affect menstrual than prolactin may also affect menstrual function.function.

* ACTH secreting tumor* ACTH secreting tumorcortisol cortisol Cushing’s Cushing’s disease.disease.

* Adenoma or adenocarcinoma of the adrenal * Adenoma or adenocarcinoma of the adrenal cortex maycortex maycortisol.cortisol.

* Ectopic production of ACTH by other tumors * Ectopic production of ACTH by other tumors such as Bronchial carcinoma or carcinoid tumorssuch as Bronchial carcinoma or carcinoid tumors

cortisol.cortisol.

CUSHING’S SYNDROMECUSHING’S SYNDROME

Cortisol excessCortisol excessprotein catabolismprotein catabolism gluconeogenesisgluconeogenesisconversion to fatconversion to fat deposition to face,neck and trunk.deposition to face,neck and trunk.Cortisol excessCortisol excessdepression of immune reaction.depression of immune reaction.Cortisol excessCortisol excessprotein catabolismprotein catabolism

wasting of limbs.wasting of limbs.

Excess of other steroids:Excess of other steroids: Estrogen Estrogen amenorrhoea amenorrhoea Androgen Androgen mild virilism mild virilism

PAUSEPAUSE

NOWNOW

HYPERANDROGENEMIAHYPERANDROGENEMIA

Hyperandrogenemia is a condition that the Hyperandrogenemia is a condition that the circulating level of testosterone, dehydro-circulating level of testosterone, dehydro-testosterone and adrostenedion, is high, testosterone and adrostenedion, is high, and may stimulate the derangement of and may stimulate the derangement of physical condition.physical condition.

Normal Androgen level: depends on the Normal Androgen level: depends on the phase of the menstrual cycle.phase of the menstrual cycle.

Increase LH level Increase LH level androgen.androgen.

CLINICAL APPEARANCESCLINICAL APPEARANCES

PCOSPCOS is is Functional derangement of the Functional derangement of the Hypothalamo-pituitary-ovarian axis Hypothalamo-pituitary-ovarian axis associated with anovulation.associated with anovulation.

LH levels relatively high, FSH LH levels relatively high, FSH

levels are relatively low.levels are relatively low.

LH:FSH ratio elevated.LH:FSH ratio elevated.

LH LH levels of Testosterone,Androstenelevels of Testosterone,Androstene

dione and DHA from Ovarium dione and DHA from Ovarium

Clinical appearances

Some of these androgens Some of these androgens estrogen estrogen (estone) in fatty tissues (Aromatization)(estone) in fatty tissues (Aromatization)

High androgen levels High androgen levels SHBG by 50% SHBG by 50% unbound, active androgensunbound, active androgens

The pathophysiology of PCOS is not clearThe pathophysiology of PCOS is not clear

(Genetic element?)(Genetic element?)

Clinical features of PCOSClinical features of PCOS

VariableVariable

The classic ‘Stein Leventhal’ syndrome,:The classic ‘Stein Leventhal’ syndrome,:

* oligomenorrhea* oligomenorrhea

* hirsutism* hirsutism

* obesity* obesity

* infertility.* infertility.

Diagnosis of PCOSDiagnosis of PCOS

No specific features of PCOS are No specific features of PCOS are diagnostic of the condition.diagnostic of the condition. on clinical on clinical grounds supported by :grounds supported by :

1.Ultrasound 1.Ultrasound **follicular cysts(follicular cysts(Ø:6-8mm)Ø:6-8mm)

**ovarian volumeovarian volume

( 25% of normal women)( 25% of normal women)

Eleveted LH:FSH ratio.Eleveted LH:FSH ratio.

Eleveted free testosterone levels.Eleveted free testosterone levels.

Decreased SHBG.Decreased SHBG.

Diagnosis of PCOSDiagnosis of PCOS

2. Infertility2. Infertilityovulation disorders.ovulation disorders.

3. Amenorrhea,3. Amenorrhea,

4. Obesity4. Obesity

5. Hirsutism5. Hirsutism

Long- term effects of PCOSLong- term effects of PCOS

Increased risk of endometrial cancer(3X)Increased risk of endometrial cancer(3X)

Increased risk of Diabetes Mellitus Increased risk of Diabetes Mellitus (Hyperinsulinemia due to insuline (Hyperinsulinemia due to insuline resistance)resistance)

Increased risk of hypertension and Increased risk of hypertension and cardiovascular disease.cardiovascular disease.

Treatment of PCOSTreatment of PCOS

Aimed at relieving symptoms and preventing Aimed at relieving symptoms and preventing long term effects.:long term effects.:

* Infertility* Infertility :1. Treat cause if known eg.:1. Treat cause if known eg.PRL.PRL. 2. Ovulation induction.2. Ovulation induction.

* Amenorrhea* Amenorrhea :1. need contraception:1. need contraception combined OC Pillscombined OC Pills 2. need no contraception2. need no contraception cyclical gestogenscyclical gestogens

Treatment of PCOSTreatment of PCOS

* Hirsutism * Hirsutism 1.Local treatment 1.Local treatment 2.Medicament treatment.:2.Medicament treatment.: * Low dose oral contraceptives* Low dose oral contraceptives * Medroxyprogesterone acetate* Medroxyprogesterone acetate * Cyproterone acetate* Cyproterone acetate * Dexamethasone* Dexamethasone * GnRH analoque (addback HRT)* GnRH analoque (addback HRT) * Ovarian Drilling,and etc.* Ovarian Drilling,and etc.

THANK YOU.THANK YOU.

THANK YOUTHANK YOU