1. NEUROENDOCRINAL
REGULATION OF
MENSTRUAL CYCLE
AMAN BALOCH

2.  NEUROENDOCRINAL
REGULATION OF MENSTRUAL
CYCLE – is a complex, genetically
determined system of inter-regulation
of genitals, central nervous system
and target organs.
Formation of reproductive system
starts antenatally and finishes at the
age of 18-21.

3. 5 LEVELS
OF MENSTRUAL CYCLE
REGULATION.
1 Target organs.
 These include external and internal genital
organs, mammary glands, bone tissue and
skin.
 Target organs have receptors for steroid
hormones.
 Influence of sex hormones on these organs
leads to formation of secondary sexual
character, cyclical processes in endometrium
and vagina.

4. 2. Ovaries.
 Steroid hormones in the ovary are synthesized
due to the action pituitary hormones.
 The hormones synthesis process inside the
ovary is called steroidogenesis.
 Adrenal glands and adipose tissue synthesize
steroid hormones too.
 Steroid hormones are synthesized from
cholesterol and have the same nature.
 Schematically this process can be represented
in the following way: cholesterol – pregnenolone
– androgens – estrogens.

5.  Ovaries synthesize 3 types of hormones:
estrogens, gestogens, androgens. Female
organism produces 3 fractions of estrogens.
 Estradiol - is the most active estrogen and is
produced by ovaries.
 Estrone – less active, mainly produced by
adipose tissue.
 Estriol – is a result of transformation of
estradiol, estrone and androgens of
epinephroses.
 Estriol is produced only during pregnancy and
has minimal hormonal activity.

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

7.  Most estrogens and androgens merge
with sex steroid-binding globulin (SSBG).
 Smaller amount of estrogens merge with
albumin and erythrocytes.
 Only one per cent of estrogens remains
free and influences the target organs.
 SSBG is synthesized by liver, its quantity
is proportional to estrogen level, and
decreases under the influence of
androgens.
 Today have been discovered 2
progesterone-binding proteins.

8. PHYSIOLOGIC EFFECTS
OF ESTROGEN
ON FEMALE ORGANISM
 Uterus. Estrogens determine the proliferation
processes in endometrium, growth of
myometrium and uterine tubes.
 Mammary glands. Stimulate growth.
 Bone tissue. Estrogens are parathormone
antagonists. They hinder development of
osteoporosis and condense growth zones in
bones.
 Cardiovascular system - i ncrease the
arterial pressure and vascular tone.

9.  Circulatory system. Increase the amount of
fibrin.
 Mineral metabolism. Estrogens influence the
natrium metabolism they attract sodium from
tissues and can cause oedemas.
 Lipidic metabolism. Increases quantity of
high-density β-lipoproteins; this has anti-
atherosclerotic effect.
 Central nervous system. Estrogens form
optimal neuropsychic condition. They change
synthesis of pituitary and hypothalamus
hormone.

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

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

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

13. 
 3. Hypophysis.
 Hypophysis is divided into 2 lobes:
anterior – adenohypophysis and posterior
– neurohypophysis.
 Adenohypophysis consists of groups of
cells, these groups of cells are responsible
for the synthesis of the following
hormones:
 growth hormone (somatotropic hormone –
STH);

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

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

16.  Hormones are not synthesized in
the posterior lobe of hypophysis.
 Oxytocin and vasopressin are
synthesized in hypothalamus, but
are accumulated in the posterior
lobe of hypophysis.

17.  4. Hypothalamus.
 Nucleuses of hypothalamus synthesize
the following neurohormones: libertines
and statines.
 The libertines stimulate
adenohypophysis, statines inhibit it.
 These hormones are called releasing
hormones.

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

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

20.  Neurohormones are synthesized not only
in hypothalamus.
 Somatostatin is synthesized in tissues of
thyroid gland, bowels.
 Other hypothalamus peptides – gastrin,
cholecystokinin, enkephaline are
synthesized by other tissues also.
 They create a regulation system called
“diffused neuroendocrinal system of
organism”.

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

22. NEUROENDOCRINAL
REGULATION
OF MENSTRUAL CYCLE.
 At the age of 10-12 years the reproductive
system starts its development.There are several
theories, which explain activation of
hypothalamo-pituitary-ovarian system.
 1.Theory of late-pubescence. According to this
theory sensitivity of hypothalamus to the steroid
hormones changes with the age. Besides,
sensitivity of ovaries to gonadotropin increases
also.

23.  2.Theory of resonance. According to
this theory the increase in electrical
activity of hypothalamus nucleuses
stimulates an increase of GN-RG
level.
 3.Theory of block release.
According to this theory at the start
of pubescence epiphysial function
decreases and hypothalamic
function increases.

24.  The activation of hypothalamus makes it
oversensitive to decrease in estrogen
concentration.
 Next, it synthesizes GN-RG, which
stimulates production of FSH and LH.
 Gonadotropins influence the process of
growth and development of follicle
(“folliculogenesis”) in ovaries.
 This descending process is called
direct relationship.

25.  The ovary of a newborn girl contains from
400.000 to 500.000 primary ovarian
follicles.
 Only 400 follicles ripen and reach the
ovulation.
 Under the influence of FSH the
development of several primari ovarian
follicles starts in the ovary.
 In the beginning they grow independently.

26.  Later on, their growth depends on the FSH level
and the sensitivity of follicle to the FSH.
 Therefore, only one follicle reaches the size of
pre-ovulatory, others atrophy.
 The wall of antrum-containing follicle has 3
sheaths: interstitial, internal theca and
granulosis.
 These sheaths have different sensitivity to
gonadotrophic hormones.
 Intersticium and theca are more sensitive to LH;
granulosis is more sensitive to FSH.

27.  Follicle synthesizes steroid hormones.
 This process is called steroidogenesis.
 Theca and intersticium synthesize steroids
up to androgen fraction; granulosis
produces estrogens.
 Increase in estrogen concentration
depresses the function of hypophysis.
 This process is called negative
inverse relationship.

29.  It takes place in the early pubertal period when
menstrual cycles are monophase.
 Positive inverse relationship is
characterized by maximum estrogen
concentration.
 Consequently honadotropines and libertines
increase dramatically.
 Ovulation follows this process.
 The ovulation process is a histochemical
process.
 Estrogens, prostaglandins and histamine
influence the sheath of the follicle and cause its
rupture.

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

31.  The ovarian cycle is a consistent process of
growth and development of follicle, ovulation,
development and death of the yellow body.
 Ovarian cycle is divided into 3 phases:
 Follicular phase is characterized by growth
and development of follicle.
 It lasts 12-14 days.
 Ovulatory phase – lasts several hours.
 Lutein phase is characterized by development
and functioning of the yellow body.

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

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

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

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

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

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

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

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

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

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

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

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

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

46. DISFUNCTIONAL UTERINE
BLEEDING
 Disfunctional,or anovulatory
uterine bleeding is associated
with anovulation caused by
impaired or unestablished
functional relationships in the
hypothalamic-pituitary-ovarian
axis.

47. Classification
 In juvenile age;
 In reproductive age;
 In the premenopausal period.

48.  Dysfunctionaluterine
bleedings may be divided
into anovulatory and
ovulatory ones.

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

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

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

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

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

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

56.  TREATMENT
 Thedoctor’s tactics largely
depend on the patient’s age.

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

58. In the child-bearing age.
 Diagnostic curettage of the uterine mucosa.
 Conservative treatment.
 Hormonal haemostasis (“medicamen-tous
curettage” synthetic progestins (norcolut,
orgametril, utrogestan, dyphaston) are
prescribed in a dose of 5-6 tablets daily is
gradually decreased to 1 tablet per day ( the
total couse of drug administration is 21 days).
 When bleeding has been arrested, cyclic
hormone therapy is administered for 6 or 9
cycles.

59. Premenopausal and
menopausal age
 Diagnostic curettage of the uterine mucosa.
 Conservative treatment.
 Hormonal haemostasis (“medicamen-tous
curettage” synthetic progestins (norcolut,
orgametril, utrogestan, dyphaston) are
prescribed in a dose of 5-6 tablets daily is
gradually decreased to 1 tablet per day ( the
total couse of drug administration is 21
days).
 The therapy is directed at regulating the
menstrual function ( in women under 45
years) or its suppression ( in women over 45
years).

60.  DYSMENORRHOEA
(ALGOMENORRHOEA)
 This term is used to painful
menstruation.
 Pain may develop before the
onset of menstruation and
continue throughout the period of
menstrual flow.

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

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

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