Disorders of menstrual function. Neuroendocrine syndromes in gynecology.
Prepared by Korda I.
The menstrual cycle is a cycle of physiological changes that occurs in fertile females.
The female menstrual cycle is determined by a complex interaction of hormones.
Menstrual cycle Timing
Follicular phase: day 1-14, menses: day 1-5
Ovulatory phase: day 14-16
Luteal phase: day 16-28
Days 1-5: Estrogen Falls, FSH Rises.
Menstrual bleeding begins on Day 1 of the cycle and lasts approximately 5 days. During the last few days prior to Day 1, a sharp fall in the levels of estrogen and progesterone signals the uterus that pregnancy has not occurred during this cycle. This signal results in a shedding of the endometrial lining of the uterus.
5. Since high levels of estrogen suppress the secretion of FSH, the drop in estrogen now permits the level of follicle stimulating hormone (FSH) to rise.
FSH stimulates follicle development.
By Day 5 to 7 of the cycle, one of these follicles responds to FSH stimulation more than the others and becomes dominant. As it does so, it begins secreting large amounts of estrogen.
6. Days 6-14: Estrogen Is Secreted, FSH Falls.
Estrogen is secreted by the follicle during this phase of the menstrual cycle. It stimulates the endometrial lining of the uterus suppresses the further secretion of FSH.
At about mid-cycle (Day 14), the estrogen helps stimulate a large and sudden release of luteinizing hormone (LH).
This LH surge, which is accompanied by a transient rise in body temperature, is a sign that ovulation is about to happen.
The LH surge causes the follicle to rupture and expel the egg into the Fallopian tube.
7. Days 14-28: Estrogen And Progesterone Secretion First Rise, then Fall.
After rupture of the follicle, it is transformed into the corpus luteum and produces progesterone.
P supports to prepare the endometrial lining for implantation of the fertilized egg.
(If the egg is fertilized, a small amount of human chorionic gonadotrophin (hCG) is released that stimulates further progesterone production.)
8.After implantation, the trophoblast will secrete human Chorionic Gonadotropin (hCG) into the maternal circulation.
keeps the corpus luteum viable.
The corpus luteum continues to produce estrogen and progesterone, which keep the endometrial lining intact.
9.If the egg is not fertilized, the corpus luteum shrinks, and the levels of estrogen and progesterone drop, the uterus sheds its lining, and menstruation begins.
In addition, with no estrogen to suppress it, FSH levels again start to rise. Thus, one cycle ends and another begins.
Flow lasts 2-7 days
Cycle 21-35 days in length
Total menstrual blood loss 20-60 mL
13. puberty is the process of physical changes by which a child's “body becomes an adult body capable of reproduction.
menarche - A woman's first menstruation is termed, and occurs typically around age 12. The menarche is one of the later stages of puberty in girls.
menopause - the end of a woman's reproductive phase, which commonly occurs somewhere between the ages of 45 and 55.
Causes giving rise to menstrual function disorders, are nervous and mental affections, stresses, psychic traumas, sexual infantilism, serious and protracted chronic diseases, chronic intoxications, feeding violations (exhaustion or obesity), endocrine diseases, gynecological diseases.
OF MENSTRUAL FUNCTION VIOLATIONS
Amenorrhea — absence of menses.
Violation of menses rhythm:
opsomenorrhea — menses come extremely rarely: in 6-8 weeks
spaniomenorrhea — the extremely long menstrual
cycle, menses come
2-4 times per year
proiomenorrhea (tachimenorrhoea) — shortened menstrual cycle, menses come in 21 days
Change of blood amount, that exudes during menses:
hypermenorrhea — a excessive amount of blood, more than 100-150 ml
hypomenorrhea — reduced amount of blood, less than 50 ml
Abnormal menses’ duration:
polymenorrhea — menses’ duration is 7-12 days
oligomenorrhea — menses duration is less than 2 days
algomenorrhea — pain during menses in genital organs region
dysmenorrhea — general disturbances during menses (headache, nausea, anorexia, raised irritability)
algodysmenorrhea — a combination of local pain and general state disturbance
Menorrhagia — the cyclic uterine bleeding, associated with menstrual cycle, lasting more than 12 days.
Methrorrhagia — acyclic uterine bleeding that is not associated with menstrual cycle.
There are distinguished hypomenstrual syndrome (opsomenorrhea, oligomenorrhea, hypomenorrhea) and the hypermenstrual syndrome (proiomenorrhea, hypermenorrhea, polymenorrhea).
According to the woman’s age the bleeding is classified:
in child age and in period of pubescence — juvenile
in women of puberty age — bleeding of reproductive or genital period
in climacteric period — climacteric bleeding
According to recurrence ovulative (cyclic, diphasic) disorders of menstrual cycle and anovulative (monophased).
Menstrual cycle irregularities:
1. abnormal frequency
Normal cycle Duration: 28 d ±5 Amount: 3-5 pads or tampons (»35 mL)
oligomenorrhea Duration > 35 days
Abnormal frequency: Duration < 22 days
Menstrual cycle irregularities:
2. abnormal amount of duration
Hypomenorrhea Amount < 2 per day
Hypermenorrhea Amount > 5 per day
16. Spotting: bleeding unrelated to menses
Metrorrhagia: > 14 days, no clear cycle
Algomenorrhea — pain during menses in genital organs region
Dysmenorrhea — general disturbances during menses (headache, nausea, anorexia, raised irritability)
Algodysmenorrhea — a combination of local pain and general state disturbance
17. Amenorrhea: absence of bleeding for more than 6 months
Primary amenorrhea is the absence of menstrual function from puberty age.
Amenorrhea is not an independent disease, but a symptom of many diseases, causing disorders of menstrual function regulation on different levels.
Forms of amenorrhea:
Genuine — absence of cyclic changes in women’s organism, most frequently associated with acute insufficiency of sexual hormones.
Falce amenorrhea (cryptomenorrhea — latent menses) — absence of menstrual blood excretion because of cyclic changes presence in organism. False amenorrhea is a clinical sign of genital organs development abnormalities — athresia of hymen or vagina, when blood, having no exit, is accumulated in vagina, uterus and uterine tubes.
Primary amenorrhea is the absence of menstrual function from puberty age.
Secondary amenorrhea is the suppression of menstrual function in woman who has menstruated before.
Physiological amenorrhea is absence of menses before puberty period, during pregnancy and lactation, in menopause period.
The pathological amenorrhea can be provoked by many causes, especially by general state changes, most frequently by endocrine diseases.
There are different forms of pathological amenorrhea: hypothalamic, pituitary, ovarian and uterine ones according to the level of menstrual function regulation disturbance.
18. Physical examination
Height and Weight
Sign of thyroid disease
Secondary sexual characteristics
Decrease in breast size or Vaginal dryness
19. Primary amenorrhea
Hypothalamic disorders 49-62 %
Pituitary 7-16 %
Ovarian disorder 10 %
21. Dysorder of Hypothalamus
Affecting Release of
Variable Estrogen Status
Chronic diseases :
Renal, Lung, Liver,
Chronic infection, Addison’s disease
Congenital adrenal hyperplasia
Androgen secreting adrenal tumor
Androgen secreting ovarian tumor
Granulosa cell tumor
Polycystic Ovary Syndrome (PCOS)
The ovaries contain many small follicles or cysts. Each has an egg, but they do not grow normally and shrink before ovulation. Each month, new follicles develop and shrink into cysts.
The fertility is reduced.
Most PCOS cases are unexplained.
• The disorder may be inherited.
• Deficiency in luteinizing hormone (LH)
Polycystic Ovary Syndrome (PCOS)
Clinical consequences of persistent anovulation
2. Menstrual dysfunction
3. Hirsutism, Alopecia, Acne
4. Risk of endometrial cancer , breast cancer
5. Risk of CVS disease
Disorder of Anterior Pituitary
Non functioning adenomas
Surgical or Radiological ablation
26. Prolactin Secreting Adenoma
Most common pituitary tumor
50% identified at autopsy
Disruption of the reproductive mechanism
Amenorrhea -Visual field defect
Medical : dopamine agonist
Acute infarction and necrosis
Hypopituitarism= early in the PP period
Failure of lactation
Loss of pubic and axillary hair
GH, Gn (FSH,LH),
ACTH, TSH (in frequency)
Disorders of the Ovary
. Chromosomal etiology
XY gonadal dysgenesis
Resistance ovarian syndrome
Premature ovarian failure
(the early depletion of ovarian follicles)
Effect of radiation and chemotherapy
Gonadal dysgenesis associated with 45,XO
Most common chromosomal abnormality in spontaneous abortion
Sexual infantilism -Less common
Short stature Autoimmune
Webbed neck CVS anomalies
cubitus valgus Renal anomalies
Premature ovarian failure
follicular depletion before age 40
physical insult :
Ovarian Resistance Syndrome
Primordial follicles fail to progress
Despite elevated gonadotropins
Disorders of the Outflow Tract or Uterus
1. Asherman’s syndrome
2. Mullerian anomalies
3. Androgen Insensitivity
4. (Testicular Feminization)
Curettage, Uterine surgery
Diagnosis : HSG Hysteroscope
33. Mullerian anomalies
Lack of Mullerian Development
Ovaries : Normal
Gonadal Sex :46xy
Blind vaginal canal
Absent or meager pubic and axillary hair
T or slightly
PMS = Recurrent psychological or physical symptoms during the luteal phase of menstrual cycle, resolves by the end of menstruation, and interferes with some aspect of function.
Premenstrual Dysphoric Disorder (PMDD) = more severe form of PMS meeting DSM-IV criteria.
About three per cent of women across all countries suffered the most severe type of PMS, called premenstrual dysphoric disorder (PMDD)
>1 somatic and affective symptom 5 days prior to menses x 3 cycles
Somatic: Depression, anger, irritability, confusion, social withdrawal, fatigue
Affective: breast tenderness, bloating, headache, swelling
Resolve within 4 days onset of menses and symptom free until day 12 of cycle
Not due to medications, drugs or ETOH use
Menstrual exacerbation of:
a. psychiatric disorder
b. Medical condition:
ii. hyper- or hypo- thyroidism
v. Chronic fatigue syndrome
Rx of mild to moderate PMS
Vit B6 during luteal phase (1 system review)
Calcium (2 large RCTs )
Evening primrose oil (weak RCTs)
Magnesium (weak RCTs)
A dysfunctional uterine bleeding (DUB) is the bleeding, not associated with organic diseases of women’s genitals, interrupted pregnancy or systemic diseases of the organism.
The dysfunctional uterine bleeding can appear at any age. Depending on the time of their onset juvenile bleeding (at child age and in period of pubescence), bleeding of reproductive period, climacteric bleeding are classified. DUB are the manifestations of initial stages of neuroendocrinological diseases, especially of blood diseases. Most frequently the dysfunctional uterine bleeding appear in young women during the formation of menstrual and reproductive function. In early reproductive phase as a damaging factor are frequently the situations, connected with mental and physical overload. chronic stress and diseases of adaptation are the pathological background on which the lesions of hormonal status develop.
In women of reproductive age the basic cause of dysfunctional uterine bleeding are inflammatory diseases. Late reproductive phase, or premenopause, comes in women at the age over 35. At this age even moderate irritants, which earlier were not the reasons of menstrual function disorders, can become starting mechanism for development of cyclic system activity dysfunction.
Disease etiology is associated with unfavourable affects of environment, psychic stresses, lesions of the ovaries’ and other endocrine glands function.
Dysfunction of hypothalamus-pituitary-ovaries-uterus system cause violation of follicle maturing. Depending on the fact that ovulation comes or not, the bleeding can be ovulative and anovulative.
Classification of dysfunctional uterine bleeding according to pathogeneses:
I. Ovulative (two-phased) according to the type of:
II. Anovulative (monophased) according to the type of:
according to onset time: cyclic (those, that come in term of next menses, but differ from it with amount of lost blood and duration); non-cyclic (appear out of menses or continue with interruptions during all the cycle).
according to patient’s age: juvenile, of reproductive age, climacteric, menopausal bleeding.
Non-ovulate uterine bleeding
Follicle atresia is a disorder of menstrual cycle, that manifests in cyclic uterine bleedings through regular time intervals, but ovulations are absent. Follicle begins its development, reaches some maturity degree, but ovulation does not come, luteal body does not appear, follicle undergoes reverse development. There is no regular hormones’ excretion (oestrogens-progesteron), secretory changes do not come in endometrium. Disease is followed by hypoestrogeny.
Clinic. Menses loose regular rhythm, intensity and duration. In response to follicle atresia and decreasing of hormones amount, in 8-16 days after bleeding onset menstrual-like reaction comes. Its mechanism is connected with blood transsudation from superficial endometrium layer vessels, where hemorrhages and regions of necrosis appear. Absence of ovulation causes infertility, that is frequently a basic patients’ complaint. The anovulate cycles can alternate with ovulate ones.
Diagnostics. For making diagnosis a continued observation of a woman and research of functional diagnostics tests indexes are necessary. Basal temperature is monophased, line is beneath 37°, the “fern” and “pupil” phenomena are weakly expressed or they are absent at all even in the middle of menstrual cycle. The colpocytological examination shows a moderate or insignificant saturation of organism with estrogens. The histological investigation proves that there are no secretory transformations of endometrium, uterine mucous membrane is in proliferation phase with tissue oedema.
Treatment. At lowered estrogen saturation the cyclic therapy with estrogens and gestagens for normalization of menstrual cycle and methods for ovulation stimulating are prescribed. The course lasts for 3-6 months.
The prolonged follicle persistence (hemorrhage methropathy, Shredder’s disease). It is developed as a result of extremely long follicle existence.
Pathogenesis. During first phase of menstrual cycle a follicle grows and develops for extremely long time. Ovulation does not come. Luteal body does not form. Tere is no progesterone production, that’s why secretion phase in endomethrium does not come. Follicle grows to significant size, sometimes a follicle cyst (a retentive formation 3 and more cm in diameter) is formed. This causes estrogens hyperproduction under the effect of which the pathological endomethrium proliferation with polyp excrescence phenomena takes place in uterus. As a result of endometrium thickening the destructive changes develop in it. necrosis and irregular desquamation appear. They are accompanied by continued bleeding, because the absence of secretory changes in uterus does not allow the functional layer of endometrium to exfoliate, as it happens during normal menses. the histological picture shows the stagnant plethora with dilation of capillaries in endometrium, blood circulation is disturbed, vessels’ permeability increases, tissual hypoxia and other dysmetabolic process develop.
Clinic. Basic sign of hemorrhage methropathy is bleeding after 1,5-2 months of amenorrhea. Period of amenorrhea corresponds to follicular development, and bleeding onset corresponds to the beginning of necrotic changes in endometrium. In such patients appears infertility, associated with absence of ovulation.
Diagnosis. Diagnosis is made on the basis of analyzing patient’s complaints. For definition of hormonal status research of ovarian function: basal temperature is lower 37°, “fern” and “pupil” phenomena are positive during the whole period of amenorrhea without cyclic variations. Colpocytological researches show an excessive saturation of the organizm with estrogens, caryopicnotic index is 60-80%. During investigation of hormones excretion with urine they find a considerable lowering of Pregnandiol excretion. During the histological research of endomethrium there is diagnosed absence of secretory transformations before expectative menses, uterine mucous membrane is in the phase of pathological proliferation, glandular-cystic hyperplasia of endometrium with necrosis, thrombosis and dystrophy phenomena is typical.
Treatment. Management the uterine bleeding arrest and normalization of menstrual cycle. Patient’s age is taken into account while choosing the treatment methods. In reproductive age and in menopause treatment begins from uterine curretage. This operation has a diagnostic and medical sense, because abrasion of the mucous membrane arrests bleeding, and histological research allows to exclude malignant tumor as a bleeding source. The curretage day is conditionally considered the first day of artificially created menstrual cycle. Later the contrainflammatoty treatment (for prevention of post-operative infection development in uterus) should be applied and menstrual cycle made regular. With this aim synthetic progestines during the three months period are taken.
According to hypoestrogeny type (shortening of the folliculin phase). Bleeding appears as a result of defective follicle maturing, the first cycle phase is shortened, ovulation takes place on the 8-10th cycle day. Menstrual cycle is shortened to 2-3 weeks, amount of excretions can be enlarged (hypermenorrhea), menses duration can be usual or elongated up to 7-10 days. Reproductive function is present.
Treatment. such patients usually do not need treatment. Sometimes at hyperpolymenorrhea uterotonics are prescribed.
According to hypogestageny type. The second place of the cycle shortens, yellow body involutes prematury, owing this gestagens are produced in insufficient amount. the secretory changes of endometrium are also insufficiently expressed, that’s why endometrium exfoliating is uneven (fig. 71).
Clinic. There are cyclic uterine bleedings, continued menses and the intervals between menses are shortened. Before menses there are greasing blood spots discharge. The reproductive function is lost, infertility develops.
Diagnosis. Basal temperature chart is diphasic. The first phase lasts for 2 weeks, the second one for 3-7 days.
Treatment. Progesterone 1ml of 1% solution for 5-6 days is prescribed in second phase of menstrual cycle. For yellow body functions enforcing vitamin E 50-60 mg and Ascorbic acid 0,5 g daily for 10 days are indicated.
According to hypergestageny type. The first phase of menstrual cycle is of full value and is finished with ovulation. Luteal body is generated. It persists for a long period and excretes an excessive amount of Progesteron. The second phase lasts for 20-25 days. Total duration of menstrual cycle is 35-40 days. Menses delay for a long period, then bleeding begins. It is prolonged up to 2-4 weeks by reason of endometrium regeneration slowing (fig. 72).
Diagnosis. Basal temperature chart is diphasic, the second phase (hypertermic) lasts for a long time, the premenstrual lowering of temperature is absent. One should make a differential diagnostics with pregnancy interruption in early terms (test on pregnancy).
Treatment is begun from the uterine curretage. Histological research shows secretory transformation of endometrium. Estrogens from the 1st till the 25th cycle day, gradually decreasing a dose are indicated. Synthetic Progestines are taken according to the scheme.
The juvenile bleeding
Non-cyclic uterine bleeding, those appear in period of pubescence, are called “juvenile” or puberty ones. Their frequency rate is from 2,5% to 10%.
Etiology. Stress affects activation of the hypothalamus-pituitary-adrenal cortex system, secretion of Gonadoliberin and gonadotropic hormones is broken. Follicles persistence that leads to changing of sexual hormones production is developed.
If in the girl’s organism there is a vitamin C deficiency, due to disbalanced diet, irregular feeding, it causes increasing of vessel walls permeability. Microcirculation and prostaglandin biosynthesis are failured. Owing this fact the blood fibrillation processes fails too.
Among the ethiological factors the infectious diseases, especially chronic tonsillitis is of a great importance. The tonsillogenous infection reduces immune reserve, influences on hypothalamic region and ovaries.
For contemporary conceptions pathogenesis of juvenile uterine bleeding is connected with synchronization violations of gonadotropic releasing factors’ excretion in blood, which affect FSH and LH production disorders. This disturbs a mechanism of follicle maturing, ovulation and yellow body formation. The follicle development is by persistence or atresia type, that creates conditions for hyperplastic processes in endometrium. bleeding appears as a reaction to decreasing of hormonal stimulation during the follicle regress.
Dysmetabolism appears in endometrium as a result of tissues hypoxia. There are dystrophic regions, necrosis with long and uneven exfoliating of endomethrium. It happens due to hardening of fibroid argirophil structure of uterine mucous membrane.
In patients with JUB not only the disorders of reproductive system are present, but the changes in hemostatic system are also frequently observed.
Clinic and diagnostics. The early beginning of pubescence and early menarche is typical, but from 15-16 years a level of sexual maturity according to signs complex is lower than in coevals. It is explained by the beginning of steroids’ synthesis failure and increasing of androgens production with progressing of disease.
In many girls with juvenile uterine bleedings the fibrous-cystic mastopathy is found, that’s why the examination of breasts in such patients is obligatory.
During the examination of external genitals its development is correct. In patients with hypoestrogenic type of bleeding mucous membrane is pale-pink, uterine cervix is conic in shape, “pupil” and “fern” symptoms are positive, bloody excretions are not significant and without mucus. During the rectal-abdominal examination uterine size corresponds to the age, an angle between the body and cervix is not expressed, ovaries are not palpated.
In patients with hyperestrogeny type of bleeding mucous membrane of vagina is pink coloured, the vaginal folds are well expressed, uterine cervix is cylindrical in shape, “pupil” and “fern” symptom +++ or ++++. There are plenty of bloody excretions with mucus admixtures. At rectal-abdominal examination uterus is slightly enlarged, an angle between its body and cervix is clearly expressed, ovaries may be enlarged comparing to the age norm.
On sonogram the uterus exceeds an age norm, ovaries are considerably greater, than in coeval healthy girls, there are small cysts compartments in them.
Estrogens secretion by urine is decreased, concentration of Progesterone in serum is also decreased.
Hysteroscopy shows hyperplasy and polyps of endometrium, rough uterine contours.
Tests of functional diagnostics: monophased basal temperature chart, CPI is 50-80% due to hyperestrogeny type and 20-40% due to hypoestrogeny type.
Taking into account a presence of hyperplastic processes in uterus in majority of girls with JUB, there is a necessity of oncologic awareness, because the cases of endometrium cancer among the girls of 16-18 years are described. The indications owing to which uterine curretage is performed in girls, are only cases of vital necessity, are reconsidered, and now it is recommended to make a diagnostic uterine curretage in patients with recidivate JUB. For making the operation the special child speculum are used, hymen previously is injected all round by Lidase, general anesthesia is used for the operation.
The blood coagulation system of the patient is estimated and she must be consulted in specialized stationary in haematologist for revealing of possible blood disease.
Treatment consists of:
prescribing of haemostatics and contractors
General treatment starts from creation of favourable work and rest regimen, creation of physical and psychic calmness, correct feeding, rich in vitamins. There is prescribed Sodium bromide and Caffeine, small doses of tranquilizers. Among physiotherapy the most procedures effective are endonasal Calcium electrophoresis, Novocaine electrophoresis, vibrate massage of the paravertebral zones. They use reflexotherapy and laser accupuncture.
Management of anaemia includes prescribing of ferrum preparations, vitamins of B group, Ascorutin, Folic acid.
Haemostatic effect is reached by using of 10% Calcium chloride solution intravenously, Pituitrin or Mammophysin 0,3-0,5 ml i/m 2-3 times a day during bleeding. For decreasing of blood loss they use fitopreparates — extract of Chamomile, viburnum, hydropepper.
Hormonal therapy foresees:
normalization of menstrual function
Hormonal therapy is prescribed on condition that the symptomatic therapy is not effective. Estrogens or combined estrogen-gestagen remedies are indicated.
Estrogenic haemostasis: 0,1% solution of Estradiol-dipropionate 1 ml intramuscularly in 3-4 hrs. or Folliculin 10 000-20 000 UA in 3-4 hrs are applied. Haemostasis is gradual during 24 hours mainly. Abrupt preparations’ cancellation can cause renewing of the bleeding, that’s why an estrogens dose is gradually decreased, to 50% daily. In 5-6 days gestagens for 6-8 days are prescribed.
Haemostasis by synthetic Progestins: monophasal estrogen-gestagen remedies (Bisecurin, Non-Ovlon, Ovulen) are taken in dose of 2-3 tabl. per day till the bleeding stops, then the dose to 1 tabl. daily is reduced. The medicine is used for 15-20 days more (1 tabl. per day). In 3-4 days after cancellation menstrual-like bleeding comes.
Surgical treatment — uterine curretage is indicated in case of disease duration with frequent relapses for more than 2 years. It is a medically-diagnostic procedure allowing to achieve haemostasis and to examine the endomethrium (in general majority of patients its hyperplasy is found).
Correcting hormone therapy. Taking into account a hyperestrogenic type of bleeding with progesterone deficit and shortening of the luteal phase, for normalization of menstrual function gestagen preparations are indicated.
The mechanism of their action is based on gestagens ability to stimulate secretion phase in endomethrium and normal (desquamation of functional layer (gestagenic curettage). They use 17-hydroxyprogesterone-capronate 12,5% 1 ml intramuscularly once for 8 days before expectative menses. Such cure takes 3-4 months. after the treatment a FSH and LH correlation can adjust, ovulatory cycles can appear.
For renewing of normal menstrual function application of combined estrogen-gestagen preparations during 4-6 months is prescribed. They are used after hormonal or surgical haemostasis.