Neuro-Endocrinal regulation of Menstrual cycle

NEUROENDOCRINALNEUROENDOCRINAL
REGULATION OFREGULATION OF
MENSTRUAL CYCLEMENSTRUAL CYCLE

 NEUROENDOCRINALNEUROENDOCRINAL
REGULATION OFREGULATION OF
MENSTRUAL CYCLEMENSTRUAL CYCLE –– is ais a
complex, genetically determinatecomplex, genetically determinate
system of inter-control of genitals,system of inter-control of genitals,
central nervous system and targetcentral nervous system and target
organs. Formation of reproductiveorgans. Formation of reproductive
system starts in antenatally andsystem starts in antenatally and
finishes at the age of 18-21.finishes at the age of 18-21.

THERE ARE 5 LEVELSTHERE ARE 5 LEVELS
OF MENSTRUAL CYCLEOF MENSTRUAL CYCLE
REGULATION.REGULATION.
1 Target organs.1 Target organs.
 They include external and internal genitalThey include external and internal genital
organs, mammary glands, bone tissue andorgans, mammary glands, bone tissue and
skin.skin.
 Target organs have receptors for steroidTarget organs have receptors for steroid
hormones.hormones.
 Due to the influence of sex hormones onDue to the influence of sex hormones on
these organs there originates the formation ofthese organs there originates the formation of
secondary sexual character, cyclical processessecondary sexual character, cyclical processes
in endometrium, vagina.in endometrium, vagina.

2. Ovaries.2. Ovaries.
 Steroid hormones in the ovary are beingSteroid hormones in the ovary are being
synthesized due to the action pituitarysynthesized due to the action pituitary
hormones.hormones.
 The hormones synthesis process inside theThe hormones synthesis process inside the
ovary was entitled steroidogenesis.ovary was entitled steroidogenesis.
 Adrenal glands and adipose tissue synthesizeAdrenal glands and adipose tissue synthesize
steroid hormones also.steroid hormones also.
 Steroid hormones are being synthesized fromSteroid hormones are being synthesized from
cholesterol and have the same nature.cholesterol and have the same nature.
 Schematically this process can be representedSchematically this process can be represented
in the following way: cholesterol – pregnenolonein the following way: cholesterol – pregnenolone
– androgens – estrogens.– androgens – estrogens.

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 Ovaries synthesize 3 types of hormones:Ovaries synthesize 3 types of hormones:
estrogens, gestogens, androgens. Femaleestrogens, gestogens, androgens. Female
organism producer 3 fractions of estrogens.organism producer 3 fractions of estrogens.
 EstradiolEstradiol -- is the most active one and is beingis the most active one and is being
produced by ovaries.produced by ovaries.
 EstroneEstrone –– less active, basically produced byless active, basically produced by
adipose tissue.adipose tissue.
 EstriolEstriol –– is a result of transformation ofis a result of transformation of
estradiol, estrone and androgens ofestradiol, estrone and androgens of
epinephroses. Estriol is major hormone ofepinephroses. Estriol is major hormone of
pregnancy with minimal hormonal activity.pregnancy with minimal hormonal activity.

 Progesterone –Progesterone – is hormone of yellowis hormone of yellow
body of ovary and is a gestogen.body of ovary and is a gestogen.
 Major androgen of ovary is aMajor androgen of ovary is a
testosteronetestosterone, which is produced by cells, which is produced by cells
of internal theca. Testosterone is not veryof internal theca. Testosterone is not very
active.active.
 Under the influence of enzyme 5-α-Under the influence of enzyme 5-α-
reductase, it is transformed into morereductase, it is transformed into more
active hormone – dehydrotestosterone.active hormone – dehydrotestosterone.

 Most estrogens and androgens mergeMost estrogens and androgens merge
with sex steroid-binding globulin (SSBG).with sex steroid-binding globulin (SSBG).
 Less amount of estrogens merge withLess amount of estrogens merge with
albumin and erythrocytes.albumin and erythrocytes.
 Only one percent of estrogens remainsOnly one percent of estrogens remains
free and influences the target organs.free and influences the target organs.
 SSBG is synthesized by liver, its quantitySSBG is synthesized by liver, its quantity
is proportional to estrogen level, andis proportional to estrogen level, and
decreases under the influence ofdecreases under the influence of
androgens.androgens.
 Today there are discovered 2Today there are discovered 2
progesterone-binding proteins.progesterone-binding proteins.

PHYSIOLOGIC EFFECTSPHYSIOLOGIC EFFECTS
OF ESTROGENOF ESTROGEN
ON FEMALE ORGANISMON FEMALE ORGANISM
 Uterus.Uterus. Estrogens determine the proliferationEstrogens determine the proliferation
processes in endometrium, growth ofprocesses in endometrium, growth of
myometrium and uterine tubes.myometrium and uterine tubes.
 Mammary glands.Mammary glands. Stimulate growth.Stimulate growth.
 Bone tissue.Bone tissue. Estrogens are parathormoneEstrogens are parathormone
antagonists. They hinder development ofantagonists. They hinder development of
osteoporosis and condense growth zones inosteoporosis and condense growth zones in
bones.bones.
 Cardiovascular system - iCardiovascular system - i ncreases thencreases the
arterial pressure and vascular tone.arterial pressure and vascular tone.

 Circulatory system.Circulatory system. Increases amount ofIncreases amount of
fibrin.fibrin.
 Mineral metabolism.Mineral metabolism. Estrogens influence theEstrogens influence the
natrium metabolism they attract sodium fromnatrium metabolism they attract sodium from
tissues and can cause the edemas.tissues and can cause the edemas.
 Lipidic metabolism.Lipidic metabolism. Increases quantity ofIncreases quantity of
high-density β-lipoproteins this is anti-high-density β-lipoproteins this is anti-
atherosclerotic effect.atherosclerotic effect.
 Central nervous system.Central nervous system. Estrogens shapeEstrogens shape
optimal neuropsychic. They change synthesis ofoptimal neuropsychic. They change synthesis of
pituitary and hypothalamus hormone.pituitary and hypothalamus hormone.

PHYSIOLOGIC EFFECTSPHYSIOLOGIC EFFECTS
OF PROGESTERONE.OF PROGESTERONE.
 Uterus.Uterus. In case of sufficient concentration ofIn case of sufficient concentration of
estrogens, progesterone exerts influence uponestrogens, progesterone exerts influence upon
tissues.tissues.
 Progesterone creates the evident anti-Progesterone creates the evident anti-
proliferative effect and conditions the secretionproliferative effect and conditions the secretion
processes in endometrium.processes in endometrium.
 Besides, progesterone furthers myometriumBesides, progesterone furthers myometrium
growth.growth.
 Mammary gland.Mammary gland. Along with estrogens andAlong with estrogens and
prolactin, progesterone conditions the tissueprolactin, progesterone conditions the tissue
development of. Besides, progesterone furthersdevelopment of. Besides, progesterone furthers
lactation.lactation.

 Cardiovascular system.Cardiovascular system. ProgesteroneProgesterone
decreases vessels tone and arterialdecreases vessels tone and arterial
pressure.pressure.
 Circulatory system.Circulatory system. Progesterone doesProgesterone does
not influence the amount of fibrin.not influence the amount of fibrin.
 Mineral metabolism.Mineral metabolism. Progesterone hasProgesterone has
diuretic effect.diuretic effect.
 Central nervous system.Central nervous system.
Progesterone may cause depressions. ItProgesterone may cause depressions. It
shows evident anti-gonadotrophic action.shows evident anti-gonadotrophic action.

EFFECTS OFEFFECTS OF
ANDROGENS.ANDROGENS.
 - Androgens is normal concentration are- Androgens is normal concentration are
synergists of estrogens.synergists of estrogens.
 - In high concentrations androgens show evident- In high concentrations androgens show evident
anti-gonadotrophic action and further theanti-gonadotrophic action and further the
development of secondary male sexualdevelopment of secondary male sexual
characters.characters.
 - During antenatal and postnatal periods- During antenatal and postnatal periods
increase of level causes change of centralincrease of level causes change of central
nervous system.nervous system.


 3. Hypophysis.3. Hypophysis.
 Hypophysis is divided into 2 lobes:Hypophysis is divided into 2 lobes:
anterior – adenohypophysis and posterioranterior – adenohypophysis and posterior
– neurohypophysis.– neurohypophysis.
 Adenohypophysis consists of groups ofAdenohypophysis consists of groups of
cells, these groups of cells are responsiblecells, these groups of cells are responsible
for the synthesis of the followingfor the synthesis of the following
hormones:hormones:
 growth hormone (somatotropic hormone –growth hormone (somatotropic hormone –
STH);STH);

 thyrotropin (thyroid stimulating hormone –thyrotropin (thyroid stimulating hormone –
TSH);TSH);
 prolactin (PRL);prolactin (PRL);
 follicle-stimulating hormone (FSH);follicle-stimulating hormone (FSH);
 luteinizing hormone (LH);luteinizing hormone (LH);
 adrenocorticotropic hormone (ACTH);adrenocorticotropic hormone (ACTH);
 melanotropic hormone (MH).melanotropic hormone (MH).

 LH, FSH, PRL are major hormones whichLH, FSH, PRL are major hormones which
regulate menstrual cycle.regulate menstrual cycle.
 But it is only possible under condition ofBut it is only possible under condition of
optimal concentrations of other pituitaryoptimal concentrations of other pituitary
hormones.hormones.
 Synthesis of pituitary hormones is realizedSynthesis of pituitary hormones is realized
due to stimulating impact ofdue to stimulating impact of
hypothalamus.hypothalamus.
 PRL synthesis depends on dopaminePRL synthesis depends on dopamine
concentration.concentration.
 PRL concentration increases whenPRL concentration increases when
dopamine level decreases.dopamine level decreases.

 Hormones are not synthesized atHormones are not synthesized at
the posterior lobe of hypophysis.the posterior lobe of hypophysis.
 Oxytocin and vasopressin areOxytocin and vasopressin are
synthesized in hypothalamus, butsynthesized in hypothalamus, but
accumulated in posterior lobe ofaccumulated in posterior lobe of
hypophysis.hypophysis.

 4. Hypothalamus.4. Hypothalamus.
 Nucleuses of hypothalamus synthesizesNucleuses of hypothalamus synthesizes
the following neurohormones: libertinesthe following neurohormones: libertines
and statines.and statines.
 The libertines stimulateThe libertines stimulate
adenohypophysis, statines inhibit it.adenohypophysis, statines inhibit it.
 These hormones were entitled releasingThese hormones were entitled releasing
hormones.hormones.

 Liberines include the following hormones:Liberines include the following hormones:
 adrenocorticotropin-releasing hormoneadrenocorticotropin-releasing hormone
(ACTH-RG);(ACTH-RG);
 thyrotropin-releasing hormone (TRG);thyrotropin-releasing hormone (TRG);
 gonadotropin-releasing hormone (GN-gonadotropin-releasing hormone (GN-
RG);RG);
 growth hormone-releasing hormonegrowth hormone-releasing hormone
(somatoliberin GH-RG);(somatoliberin GH-RG);
 melanoliberin (M-RG)/melanoliberin (M-RG)/

 StatinesStatines include the followinginclude the following
hormones:hormones:
 somatostatin;somatostatin;
 dopamine (major prolactin-dopamine (major prolactin-
inhibiting factor).inhibiting factor).

 Synthesis of neurohormones descendsSynthesis of neurohormones descends
not only in hypothalamus.not only in hypothalamus.
 Somatostatin is synthesized in tissues ofSomatostatin is synthesized in tissues of
thyroid gland, bowels.thyroid gland, bowels.
 Other hypothalamus peptides – gastrin,Other hypothalamus peptides – gastrin,
cholecystokinin, enkephaline arecholecystokinin, enkephaline are
synthesized by other tissues also.synthesized by other tissues also.
 They create a regulation system entitledThey create a regulation system entitled
“diffused neuroendocrinal system of“diffused neuroendocrinal system of
organism”.organism”.

 5. Extra-hypothalamic structures.5. Extra-hypothalamic structures.
 Epiphysis, limbic system, celebrumEpiphysis, limbic system, celebrum
tonsil, hippocampus influence thetonsil, hippocampus influence the
reproductive function.reproductive function.
 They are related to extra-hypothalamicThey are related to extra-hypothalamic
structures.structures.
 Function of hypothalamus can beFunction of hypothalamus can be
stimulated or inhibited by enkephalins,stimulated or inhibited by enkephalins,
endorphins, neuropeptides.endorphins, neuropeptides.

NEUROENDOCRINALNEUROENDOCRINAL
REGULATIONREGULATION
OF MENSTRUAL CYCLE.OF MENSTRUAL CYCLE.
 At the age of 10-12 years reproductive systemAt the age of 10-12 years reproductive system
starts its development.There are severalstarts its development.There are several
theories, which explain activation oftheories, which explain activation of
hypothalamo-pituitary-ovarian system.hypothalamo-pituitary-ovarian system.
 1.Theory of after-ripening. According to this1.Theory of after-ripening. According to this
theory sensitivity of hypothalamus to the steroidtheory sensitivity of hypothalamus to the steroid
hormones changes with the age. Besides,hormones changes with the age. Besides,
sensitivity of ovaries to gonadotropin increasessensitivity of ovaries to gonadotropin increases
also.also.

 2.Theory of resonance. According to2.Theory of resonance. According to
this theory increase in electricalthis theory increase in electrical
activity of hypothalamus nucleusesactivity of hypothalamus nucleuses
stimulates an increase of GN-RGstimulates an increase of GN-RG
level.level.
 3.Theory of block release.3.Theory of block release.
According to this theory at the startAccording to this theory at the start
of pubescence epiphysis functionof pubescence epiphysis function
decreases and hypothalamusdecreases and hypothalamus
function increases.function increases.

 Activation of hypothalamus makes itActivation of hypothalamus makes it
drastically sensible to decrease indrastically sensible to decrease in
estrogen’s concentration.estrogen’s concentration.
 Next, it synthesized GN-RG, whichNext, it synthesized GN-RG, which
stimulates production of FSH and LH.stimulates production of FSH and LH.
 Gonadotropins influence the process ofGonadotropins influence the process of
growth and development of folliclegrowth and development of follicle
(“folliculogenesis”) in ovaries.(“folliculogenesis”) in ovaries.
 This descending process is entitledThis descending process is entitled
direct relationship.direct relationship.

 Ovary of newborn girl contains 400-500Ovary of newborn girl contains 400-500
thousands of primary ovarian follicle.thousands of primary ovarian follicle.
 Only 400 follicles ripen and reach theOnly 400 follicles ripen and reach the
ovulation.ovulation.
 In the ovary there starts the developmentIn the ovary there starts the development
of several primary ovarian follicles underof several primary ovarian follicles under
the influence of FSH.the influence of FSH.
 In the beginning they grow independently.In the beginning they grow independently.

 Later on, their growth depends on the FSH levelLater on, their growth depends on the FSH level
and the sensitivity of follicle to the FSH.and the sensitivity of follicle to the FSH.
 Therefore, only one follicle amounts to the sizeTherefore, only one follicle amounts to the size
of pre-ovulatory, other undergo atrophy.of pre-ovulatory, other undergo atrophy.
 Wall of antrum-containing follicle has 3 sheaths:Wall of antrum-containing follicle has 3 sheaths:
interstitial, internal theca and granulosis.interstitial, internal theca and granulosis.
 These sheaths have differing sensibility toThese sheaths have differing sensibility to
gonadotropic hormones.gonadotropic hormones.
 Intersticium and theca are more sensible to LH,Intersticium and theca are more sensible to LH,
and granulosis – to FSH.and granulosis – to FSH.

 Follicle synthesizes steroid hormones.Follicle synthesizes steroid hormones.
 This process is called steroidogenesis.This process is called steroidogenesis.
 This process is integrated: theca andThis process is integrated: theca and
intersticium synthesize steroids up tointersticium synthesize steroids up to
androgen fraction, and granulosisandrogen fraction, and granulosis
produces estrogens.produces estrogens.
 Increase in estrogen’s concentrationIncrease in estrogen’s concentration
depresses function of hypophysis.depresses function of hypophysis.
 This process is called negativeThis process is called negative
inverse relationship.inverse relationship.

 It takes place in the early pubertal period whenIt takes place in the early pubertal period when
menstrual cycles are monophase.menstrual cycles are monophase.
 Positive inverse relationship isPositive inverse relationship is
 characterized by maximum estrogen’scharacterized by maximum estrogen’s
concentration.concentration.
 Consequently there occurs keen increase ofConsequently there occurs keen increase of
honadotropines and libertines.honadotropines and libertines.
 Ovulation follows this process.Ovulation follows this process.
 Ovulation process is a histochemical process.Ovulation process is a histochemical process.
 Estrogens, prostaglandins and histamineEstrogens, prostaglandins and histamine
influence the sheath of follicle and cause itsinfluence the sheath of follicle and cause its
rupture.rupture.

 Granulosis cells are transformed into theGranulosis cells are transformed into the
yellow body under the influence of LHyellow body under the influence of LH
after ovulation.after ovulation.
 The yellow body synthesizesThe yellow body synthesizes
progesterone.progesterone.
 Increase of progesterone inhibits theIncrease of progesterone inhibits the
synthesis of LH.synthesis of LH.
 This causes the death of the yellow body.This causes the death of the yellow body.

 Ovarian cycle isOvarian cycle is a consistent process ofa consistent process of
growth and development of follicle, ovulation,growth and development of follicle, ovulation,
development and death of the yellow body.development and death of the yellow body.
 Ovarian cycle is divided into 3 phases:Ovarian cycle is divided into 3 phases:
 Follicular phaseFollicular phase is characterized by growthis characterized by growth
and development of follicle.and development of follicle.
 It lasts 12-14 days.It lasts 12-14 days.
 Ovulatory phaseOvulatory phase – it several hours.– it several hours.
 Lutein phaseLutein phase is characterized by developmentis characterized by development
and functioning of the yellow body.and functioning of the yellow body.

 Uterine cycle isUterine cycle is a cyclic process in the ovary,a cyclic process in the ovary,
which causes cyclic changes in thewhich causes cyclic changes in the
endometrium. It has 4 phases:endometrium. It has 4 phases:
 Desquamation.Desquamation. Decrease of steroid hormonesDecrease of steroid hormones
causes spasm, ischemia and rejection spiroidcauses spasm, ischemia and rejection spiroid
artery of decidual sphere of endometrium.artery of decidual sphere of endometrium.
 First day of desquamation corresponds to theFirst day of desquamation corresponds to the
first day of menstruation and menstrual cycle.first day of menstruation and menstrual cycle.
 Regeneration.Regeneration. It corresponds to the earlyIt corresponds to the early
period of follicular phase in the ovary.period of follicular phase in the ovary.
 Regeneration lasts 4-5 days.Regeneration lasts 4-5 days.
 It starts with epithelization of endometrium.It starts with epithelization of endometrium.

 Proliferation.Proliferation. It lasts 5-7 days and results inIt lasts 5-7 days and results in
ovulation.ovulation.
 It corresponds to the late period of follicularIt corresponds to the late period of follicular
phase in the ovary.phase in the ovary.
 Is characterized by proliferation of epitheliumIs characterized by proliferation of epithelium
and development of spiroid arteries.and development of spiroid arteries.
 Secretion.Secretion. It corresponds to lutein phase in theIt corresponds to lutein phase in the
ovary. It lasts 10-12 days.ovary. It lasts 10-12 days.
 The process of proliferation is superseded byThe process of proliferation is superseded by
secretion.secretion.
 If pregnancy did not take place, cyclic processesIf pregnancy did not take place, cyclic processes
in the system uterus-ovaries-hypothalamic-in the system uterus-ovaries-hypothalamic-
pituitary system repeat.pituitary system repeat.

MENSTRUAL DISORDERSMENSTRUAL DISORDERS
ETIOLOGYETIOLOGY
 Nervous diseases.Nervous diseases.
 Mental diseases.Mental diseases.
 Malnutrition.Malnutrition.
 Some occupational hazards.Some occupational hazards.
 Systemic and gynecologic inflammatory diseases.Systemic and gynecologic inflammatory diseases.
 Illness of the haemopoiesis, cardiovascular and otherIllness of the haemopoiesis, cardiovascular and other
systems.systems.
 Gynecologic operations.Gynecologic operations.
 Puberty disorders.Puberty disorders.
 Age-specific reconstruction of the functional state inAge-specific reconstruction of the functional state in
hypothalamic-pituitary-ovarian axis in the menopause.hypothalamic-pituitary-ovarian axis in the menopause.

AMENORRHOEAAMENORRHOEA
 Pathological primary amenorrhoea – when thePathological primary amenorrhoea – when the
patient has never menstruated.patient has never menstruated.
 Pathological secondary amenorrhoea – whenPathological secondary amenorrhoea – when
the periods are absent for more than 6 months.the periods are absent for more than 6 months.
 Physiological amenorrhoea – before puberty,Physiological amenorrhoea – before puberty,
during pregnancy and lactation, and after theduring pregnancy and lactation, and after the
menopause.menopause.
 False amenorrhoea – when the flow does notFalse amenorrhoea – when the flow does not
escape because of some obstruction.escape because of some obstruction.
 True amenorrhoea – when the endometrialTrue amenorrhoea – when the endometrial
cycle is absent.cycle is absent.

TRUE PATHOLOGICALTRUE PATHOLOGICAL
AMENORRHOEAAMENORRHOEA
1.Uterine disorders.1.Uterine disorders.
 the uterus may be congenitally defective;the uterus may be congenitally defective;
 the endometrium atrophies afterthe endometrium atrophies after
irradiation with X-ray or radium, andirradiation with X-ray or radium, and
hysterectomy.hysterectomy.

2. Ovarian disorders.2. Ovarian disorders.
 failure of ovarian development occurs in cases offailure of ovarian development occurs in cases of
gonadal dysgenesis;gonadal dysgenesis;
 Stein-LeventhalStein-Leventhal syndrome is a disorder of unknownsyndrome is a disorder of unknown
cause.cause.
 After some years of normal menstruationAfter some years of normal menstruation
amenorrhoea occurs with hirsuties.amenorrhoea occurs with hirsuties.
 Both ovaries are enlarged and contain multipleBoth ovaries are enlarged and contain multiple
small follicular cysts.small follicular cysts.
 There is a block in the normal conversion ofThere is a block in the normal conversion of
progesterone to estrogen so that an intermediateprogesterone to estrogen so that an intermediate
androgen substance androstendione appears inandrogen substance androstendione appears in
excess.excess.
 The urinary excretion of estrogens is normal or low,The urinary excretion of estrogens is normal or low,
while that of pregnantriol (a metabolic product ofwhile that of pregnantriol (a metabolic product of
certain androgens) is raised;certain androgens) is raised;
 arrhenoblastoma is a very rare cause of amenorrhoea;arrhenoblastoma is a very rare cause of amenorrhoea;
 ovarian infections or new growths as processesovarian infections or new growths as processes
destroying all ovarian tissue.destroying all ovarian tissue.

3. Pituitary disorders.3. Pituitary disorders.
 There is of production of gonadotrophicThere is of production of gonadotrophic
hormones.hormones.
 Amenorrhoea is one aspect of generalAmenorrhoea is one aspect of general
disorders and the gynecologist is seldomdisorders and the gynecologist is seldom
responsible for treatment.responsible for treatment.
 Pituitary infantilism (Levi-Loraine syndrome).Pituitary infantilism (Levi-Loraine syndrome).
The adult resembles a child. No effectiveThe adult resembles a child. No effective
treatment is known.treatment is known.
 Pituitary cachexia (Simmond’s disease). ThisPituitary cachexia (Simmond’s disease). This
is usually due to ischemic necrosis of theis usually due to ischemic necrosis of the
pituitary glands (hypophysis) due topituitary glands (hypophysis) due to
thrombosis of pituitary vessels afterthrombosis of pituitary vessels after
postpartum hemorrhage and collapse.postpartum hemorrhage and collapse.
 Failure of lactation is followed by genitalFailure of lactation is followed by genital
atrophy, loss of pubic hair, weakness,atrophy, loss of pubic hair, weakness,
anorexia.anorexia.

 Treatment with cortisone, thyroxin and anabolicTreatment with cortisone, thyroxin and anabolic
steroids may cause some improvement.steroids may cause some improvement.
 Adipogenital dystrophy is characterized byAdipogenital dystrophy is characterized by
dwarfing, adiposity and genital infantilism, and isdwarfing, adiposity and genital infantilism, and is
usually caused by a craniopharyngioma thatusually caused by a craniopharyngioma that
involves the pituitary gland and hypothalamus.involves the pituitary gland and hypothalamus.
The treatment is surgical.The treatment is surgical.
 In acromegaly the eosinophilic adenoma of theIn acromegaly the eosinophilic adenoma of the
pituitary gland may destroy the gonadotrophicpituitary gland may destroy the gonadotrophic
cells, and the same may happen with othercells, and the same may happen with other
pituitary tumors.pituitary tumors.
 Small pituitary adenoma may secrete prolactinSmall pituitary adenoma may secrete prolactin
and cause amenorrhoea with galactorrhoea.and cause amenorrhoea with galactorrhoea.

4.Other endocrine disorders.4.Other endocrine disorders.
 Amenorrhoea occurs:Amenorrhoea occurs:
 in severe cases of hyperthyreoidism,in severe cases of hyperthyreoidism,
myxoedema and cretinism;myxoedema and cretinism;
 in some cases of diabetes;in some cases of diabetes;
 in Addison’s disease;in Addison’s disease;
 with adrenocortical tumors orwith adrenocortical tumors or
hyperplasia.hyperplasia.

 5. Nervous disorders5. Nervous disorders (stress(stress
or hypothalamic amenorrhoea).or hypothalamic amenorrhoea).
This is the commonest type ofThis is the commonest type of
secondary amenorrhoea, andsecondary amenorrhoea, and
may be the result of emotionalmay be the result of emotional
disturbances.disturbances.

 6.Disorders of general health and6.Disorders of general health and
nutrition.nutrition. Any chronic or severe illnessAny chronic or severe illness
(including nutritional deficiency) will(including nutritional deficiency) will
cause amenorrhoea.cause amenorrhoea.
 7.Oral contraception.7.Oral contraception. A delayed firstA delayed first
period is common after stopping oralperiod is common after stopping oral
contraception. More prolongedcontraception. More prolonged
amenorrhoea sometimes occurs.amenorrhoea sometimes occurs.

DIAGNOSISDIAGNOSIS
 General examination;General examination;
 Special gynecologic examination;Special gynecologic examination;
 Ultrasonic;Ultrasonic;
 X-ray;X-ray;
 Hormonal tests.Hormonal tests.

TREATMENTTREATMENT
 Sedative therapy;Sedative therapy;
 Vitamin therapy;Vitamin therapy;
 Adequate nutrition, a special diet intended toAdequate nutrition, a special diet intended to
decrease the body weight;decrease the body weight;
 Physiotherapy (endonasal electrophoresis withPhysiotherapy (endonasal electrophoresis with
2% solution of vitamin B1, 0.25% solution of2% solution of vitamin B1, 0.25% solution of
dyphenhydramine hydrochloride).dyphenhydramine hydrochloride).
 Drugs suppressing prolactin secretionDrugs suppressing prolactin secretion
(bromocriptine, parlodel, dostineks).(bromocriptine, parlodel, dostineks).
 Hormonal therapy of the cyclic hormonesHormonal therapy of the cyclic hormones
(estrogens followed by progesterone).(estrogens followed by progesterone).

DISFUNCTIONAL UTERINEDISFUNCTIONAL UTERINE
BLEEDINGBLEEDING
 Disfunctional, or anovulatoryDisfunctional, or anovulatory
uterine bleeding is associateduterine bleeding is associated
with anovulation caused bywith anovulation caused by
impaired or unestablishedimpaired or unestablished
functional relationships in thefunctional relationships in the
hypothalamic-pituitary-ovarianhypothalamic-pituitary-ovarian
axis.axis.

ClassificationClassification
 In juvenile age;In juvenile age;
 In reproductive age;In reproductive age;
 In the premenopausal period.In the premenopausal period.

 Dysfunctional uterineDysfunctional uterine
bleedings may be dividedbleedings may be divided
into anovulatory andinto anovulatory and
ovulatory ones.ovulatory ones.

 Anovulatory bleedings are induced by theAnovulatory bleedings are induced by the
absence of ovulation and luteal phase ofabsence of ovulation and luteal phase of
the cycle.the cycle.
 Anovulatory uterine bleeding develops inAnovulatory uterine bleeding develops in
patients with:patients with:
 persistence of an ovarian follicle;persistence of an ovarian follicle;
persistent follicles release a large numberpersistent follicles release a large number
of estrogens;of estrogens;
 atresia of a few follicles; atresia of someatresia of a few follicles; atresia of some
small follicles is associated withsmall follicles is associated with
hypoestrogenism.hypoestrogenism.

 Both account for continuous, monotonousBoth account for continuous, monotonous
secretion of estrogens.secretion of estrogens.
 Ovulation does not occur and the corpus luteumOvulation does not occur and the corpus luteum
fails to form.fails to form.
 Excessive proliferation of the endometriumExcessive proliferation of the endometrium
occurs as a result of prolongedoccurs as a result of prolonged
exposure to estrogens in both processes.exposure to estrogens in both processes.
 Persistent and atretic follicles undergoPersistent and atretic follicles undergo
involution.involution.
 The level of hormones (estrogens) is decreasedThe level of hormones (estrogens) is decreased
in the blood, and bleeding develops.in the blood, and bleeding develops.

 Circulation in the endometrium isCirculation in the endometrium is
impaired, the capillary permeability isimpaired, the capillary permeability is
decreased, and the sites of dystrophy anddecreased, and the sites of dystrophy and
necrosis are manifested.necrosis are manifested.
 The necrotic mucosa is rejected slowly,The necrotic mucosa is rejected slowly,
which causes prolonged bleeding.which causes prolonged bleeding.
 Dysfunctional uterine bleedings are notDysfunctional uterine bleedings are not
attended with pain.attended with pain.

CLINICAL PICTURECLINICAL PICTURE
 Amenorrhoea: in 4-8 weeks in persistent follicle;Amenorrhoea: in 4-8 weeks in persistent follicle;
3-4 months in atretic follicles;3-4 months in atretic follicles;
 Bleedings are more abundant in persistentBleedings are more abundant in persistent
follicles, being occasionally profuse;follicles, being occasionally profuse;
 Anemia;Anemia;
 Decrease the patient’s working capacity;Decrease the patient’s working capacity;
 General fatigue;General fatigue;
 Headache;Headache;
 Poor appetite;Poor appetite;
 Sleep;Sleep;
 Pale skin;Pale skin;
 Tachycardia;Tachycardia;
 Decreased blood pressure.Decreased blood pressure.

DIAGNOSISDIAGNOSIS
 Diagnosis is based on general andDiagnosis is based on general and
gynecologic examination. At generalgynecologic examination. At general
examination one should pay attention toexamination one should pay attention to
the typical sings:the typical sings:
 bleedings that follow the suppression ofbleedings that follow the suppression of
menses;menses;
 monophase basal body temperature;monophase basal body temperature;
 high or low karyopycnotic index.high or low karyopycnotic index.

 Dysfunctional uterine bleedings should beDysfunctional uterine bleedings should be
differentiated from many disease formsdifferentiated from many disease forms
that are attended with bleedings:that are attended with bleedings:
 abortions;abortions;
 interrupted fallopian pregnancy;interrupted fallopian pregnancy;
 tumors of the uterus.tumors of the uterus.

 TREATMENTTREATMENT
 The doctor’s tactics largelyThe doctor’s tactics largely
depend on the patient’s age.depend on the patient’s age.

Juvenile bleedings.Juvenile bleedings.
 Conservative treatment (use coagulants,Conservative treatment (use coagulants,
hemostatic agents, stimulants of uterinehemostatic agents, stimulants of uterine
contractility).contractility).
 Hormonal haemostasis (“medicamentousHormonal haemostasis (“medicamentous
curettage” synthetic estrogen-progesteroncurettage” synthetic estrogen-progesteron
drugs (logest, yrina, dgaz, ganin) aredrugs (logest, yrina, dgaz, ganin) are
prescribed in a dose of 5-6 tablets daily isprescribed in a dose of 5-6 tablets daily is
gradually decreased to 1 tablet per day ( thegradually decreased to 1 tablet per day ( the
total couse of drug administration is 21total couse of drug administration is 21
days).days).
 Diagnostic curettage of the uterine mucosa.Diagnostic curettage of the uterine mucosa.
 When bleeding has been arrested, cyclicWhen bleeding has been arrested, cyclic
hormone therapy is administered for 6 or 9hormone therapy is administered for 6 or 9
cycles.cycles.

In the child-bearing age.In the child-bearing age.
 Conservative treatment.Conservative treatment.
 Hormonal haemostasis (“medicamen-tousHormonal haemostasis (“medicamen-tous
curettage” synthetic progestins (norcolut,curettage” synthetic progestins (norcolut,
orgametril, utrogestan, dyphaston) areorgametril, utrogestan, dyphaston) are
total couse of drug administration is 21 days).total couse of drug administration is 21 days).
 When bleeding has been arrested, cyclicWhen bleeding has been arrested, cyclic
hormone therapy is administered for 6 or 9hormone therapy is administered for 6 or 9
cycles.cycles.

Premenopausal andPremenopausal and
menopausal agemenopausal age
 Conservative treatment.Conservative treatment.
 Hormonal haemostasis (“medicamen-tousHormonal haemostasis (“medicamen-tous
curettage” synthetic progestins (norcolut,curettage” synthetic progestins (norcolut,
orgametril, utrogestan, dyphaston) areorgametril, utrogestan, dyphaston) are
total couse of drug administration is 21total couse of drug administration is 21
days).days).
 The therapy is directed at regulating theThe therapy is directed at regulating the
menstrual function ( in women under 45menstrual function ( in women under 45
years) or its suppression ( in women over 45years) or its suppression ( in women over 45
years).years).

 DYSMENORRHOEADYSMENORRHOEA
(ALGOMENORRHOEA)(ALGOMENORRHOEA)
 This term is used to painfulThis term is used to painful
menstruation.menstruation.
 Pain may develop before thePain may develop before the
onset of menstruation andonset of menstruation and
continue throughout the period ofcontinue throughout the period of
menstrual flow.menstrual flow.

 Sometimes, pain is severe and attendedSometimes, pain is severe and attended
by nausea, vomiting and otherby nausea, vomiting and other
disturbances, which reduce the patient’sdisturbances, which reduce the patient’s
working capacity.working capacity.
 In many cases dysmenorrhoea is just aIn many cases dysmenorrhoea is just a
manifestation of systemic diseases.manifestation of systemic diseases.
 It may be attributed to retroflexion orIt may be attributed to retroflexion or
anteflexion of the uterus, cicatricialanteflexion of the uterus, cicatricial
changes, and narrowing of the cervicalchanges, and narrowing of the cervical
canal.canal.

 Primary and secondary forms ofPrimary and secondary forms of
dysmenorrhoea are distinguished.dysmenorrhoea are distinguished.
 The formes does not appear to be linkedThe formes does not appear to be linked
to any organic disease and is congenital.to any organic disease and is congenital.
 The latter develops in women withThe latter develops in women with
previously normal menstruations.previously normal menstruations.
 Secondary dysmenorrhoea may beSecondary dysmenorrhoea may be
related to inflammatory processes,related to inflammatory processes,
endometriosis, and genital tumors.endometriosis, and genital tumors.

Treatment.Treatment.
 Anti-inflammatory drugs.Anti-inflammatory drugs.
 Hormonal drugs.Hormonal drugs.
 Surgical treatment.Surgical treatment.
 Sedative drugs.Sedative drugs.
 Vitamin therapy.Vitamin therapy.

Neuro-Endocrinal regulation of Menstrual cycle

Neuro-Endocrinal regulation of Menstrual cycle

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