1. MENSTRUAL CYCLE DISORDERS DIAGNOSIS
PETR KREPELKA 1

2. NORMAL MENSTRUAL CYCLE
The mean duration of the MC
Mean 28 days (only 15% of ♀)
Range 21-35
The average duration of the MC
3-8 days
The normal estimated blood loss?
Approximately 30 ml
Ovulation occurs
Usually day 14
34 hrs after the onset of mid-cycle LH surge 2

3. NORMAL MENSTRUAL CYCLE
Regulation of MC
Interaction between hypothalamus, pituitary & ovaries
Menarche
12.7
Menopause
51.4 3

4. HYPOTHALAMIC ROLE IN THE MENSTRUAL CYCLE
The hypothalamus secretes GnRH in a pulsatile fashion
GnRH activity is first evident at puberty
Follicular phase GnRH pulses occur hourly
Luteal phase GnRH pulses occur every minutes
Loss of pulsatility down regulation of pituitary receptors   secretion of gonadotropins
Release of GnRH is modulated by –ve feedback by:
steroids
gonadotropins
Release of GnRH is modulated by external neural signals 4

5. PHASES OF THE MENSTRUAL CYCLE
Ovulation divides the MC into two phases:
1-FOLLICULAR PHASE
-Begins with menses on day 1 of the menstrual cycle
& ends with ovulation
▲RECRUITMENT
FSH  maturation of a cohort of ovarian
follicles “recruitment”
 only one reaches maturity 5

6. FOLLICULAR PHASE
MATURATION OF THE FOLLICLE (FOLLICULOGENESIS) - FSH  primordial follicle (oocyte arrested in the diplotene stage of the 1st meiotic division surrounded by a single layer of granulosa cells)   1ry follicle (oocyte surrounded by a single layer of granulosa cells basement membrane & theca cells)   2ry follicle or preantral follicle (oocyte surrounded by zona pellucida , several layers of granulosa cells & theca cells)

7. FOLLICULOGENESIS
 tertiary or antral follicle 2ry follicle accumulate fluid in a cavity “antrum” oocyte is in eccentric position surrounded by granulosa cells “cumulous oophorus”

8. FOLLICULOGENESIS continue to thrive
SELECTION
-Selection of the dominant follicle occurs day 5-7
-It depends on
- the intrinsic capacity of the follicle to
synthesize estrogen
-high est/and ratio in the follicular fluid
-As the follicle mature   estrogen  FSH
“-ve feed back on the pituitary”  the follicle
with the highest No. of FSH receptors will
continue to thrive
- The other follicles “that were recruited” will become atretic 8

9. - LH  theca cells  uptake of cholesterol & LDL 
FSH ACTIONS
-recruitement
-mitogenic effect   No. of granulosa cells
 FSH receptor
-stimulates aromatase activity  conversion of
androgens  estrogens “estrone & estradiol”
-  LH receptors
- ESTROGEN
Acts synergistically with FSH to
- induce LH receptors
- induce FSH receptors in granulosa
& theca cells
- LH  theca cells  uptake of cholesterol & LDL 
androstenedione & testosterone

10. FOLLICULOGENESIS OTHER FACTORS THAT PLAY A ROLE IN FOLLICULOGENISIS
-INHIBIN
Local peptide in the follicular fluid
-ve feed back on pituitary FSH secreation
Locally enhances LH-induced androstenedione production
-ACTIVIN
Found in follicular fluid
Stimulates FSH induced estrogen production
 gonadotropin receptors
androgen
No real stimulation of FSH secretion in vivo (bound to protein in serum)

11. PREOVULATORY PERIOD - NEGATIVE FEEDBACK ON THE PIUITARY
- estradiol & inhibin -ve feed back on pituitary   FSH
-This mechanism operating since childhood
- POSITIVE FEEDBACK ON THE PITUITARY
  estradiol (reaching a threshold concentration pg/ml, for 48 hrs )   +ve feed back on the pituitary (facilitated by low levels of progestrone)   LH surge  secretion of progestrone
Operates after puberty
+ve feed back on pituitary   FSH 11

12. PREOVULATORY PERIOD LH SURGE Lasts for 48 hrs
Ovulation occurs after 34hrs
Accompanied by rapid fall in estradiol level
Triggers the resumption of meiosis
Affects follicular wall  follicular rupture
Granulosa cells  lutenization  progestrone synthesis

13. OVULATION Gentle release of the oocyte surrounded by the cumulus
The dominant follicle protrudes from the ovarian cortex
Gentle release of the oocyte surrounded by the cumulus
granulosa cells
Mechanism of follicular rupture
1- Follicular pressure
Changes in composition of the antral fluid   colloid
osmotic pressure
2-Enzymatic rupture of the follicular wall
LH & FSH  granulosa cells  production of plasminogen activator
  plasmin   fibrinolytic activity  breake down of F. wall
LH   prostglandin E   plasminogen activator
  PG F2α   lysosomes under follicular wall 13

14. LUTEAL PHASE LASTS 14 days FORMATION OF THE CORPUS LUTEUM
After ovulation the point of rupture in the follicular wall seals
Vascular capillaries cross the basement membrane & grow into the granulosa cells  availability of LDL-cholestrole
LH  LDL binding to receptors
 3α OH steroid dehydrogenase activity
 progestrone
The luteal phase is about 14 days in length and ends with the onset of menses.
This phase includes the functional lifespan of the corpus
luteum, which supports the released ovum by secreting progesterone. Progesterone
secretion increases up to 8 days after the LH surge. Smaller
increases in 17α-hydroxyprogesterone, estradiol, and estrone occur. Progesterone
decreases before menses unless the ovum is fertilized and pregnancy
results. A serum progesterone level higher than 10 ng/mL 1 week before
menses is probably diagnostic of normal ovulation. Progestins increase basal
morning body temperature so that a “thermogenic shift” of more than 0.3° C
occurring after a nadir is a presumptive sign of ovulation. Unfortunately,
taking basal temperatures on a daily basis is tedious, subject to error, and not
very reliable 14

15. LUTEAL PHASE Marked  in progestrone secretion Progestrone actions:
-suppress follicular maturation on the
ipsilateral ovary
-thermogenic activity  basal body temp
-endometrial maturation
Progestrone peak 8 days after ovulation (D22 MC)
Corpus luteum is sustained by LH
It looses its sensitivity to gonadotropins  luteolysis 
estrogen & progestrone level  desquamation of the endometrium “menses”

16. LUTEAL PHASE estrogen & progestrone   FSH &LH
The new cycle stars with the beginning of menses
If pregnancy occurs  hCG secreation  maintain the
corpus luteum

17. ENDOMETRIAL CHANGES DURING THE MENSTRUAL CYCLE
1-Basal layer of the enometrium
-Adjacent to the mometrium
-Unresponsive to hormonal stimulation
-Remains intact throughout the menstrual cycle
2-Functional layer of the endometrium
Composed of two layers:
-zona compacta  superficial
-Spongiosum layer 17

18. ENDOMETRIAL CHANGES DURING THE MENSTRUAL CYCLE
1-Follicular /proliferative phase
Estrogen  mitotic activity in the glands & stroma 
 endometrial thickness from 2 to 8 mm
(from basalis to opposed basalis layer)
2-Luteal /secretory phase
Progesterone - Mitotic activity is severely restricted
-Endometrial glands produce then secrete
glycogen rich vacules
-Stromal edema
-Stromal cells enlargement
-Spiral arterioles develop, lengthen & coil 18

19. MENSTRUATION Periodic desquamation of the endometrium
The external hallmark of the menstrual cycle
Just before menses the endometrium is infiltrated with leucocytes
Prostaglandins are maximal in the endometrium just before menses
Prostaglandins  constriction of the spiral arterioles ischemia & desquamation
Followed by arteriolar relaxation, bleeding & tissue breakdown
When estradiol and progesterone decline, the stroma becomes edematous, endometrial and
blood vessel necrosis occurs, and bleeding ensues. Local release of prostaglandins
may initiate vasospasm with ischemic necrosis and uterine contractions
that accompany menstrual flow. Prostaglandin synthetase inhibitors can
relieve menstrual cramping. Fibrinolytic activity peaks at the time of menstruation,
accounting for the noncoagulability of menstrual blood. The histologic
changes are characteristic; therefore, endometrial biopsies can be
used to characterize the stage of the cycle and to assess the tissue response
to gonadal steroids. 19

20. Definition of normal menstruation
Regularity
Frequency - Cycle lenght
Duration of menstrual flow
Volume of menstrual flow

21. Describing normal uterine bleeding
Regularity of menstruation
Regular
Iregular
Absent
Frequency
Frequent
Normal
Infrequent

22. Describing normal uterine bleeding
Duration of menstrual flow
Prolonged
Normal
Shortened
Volume of menstrual flow
Heavy
Light

23. Nomenclature for normal menstraution
Abnormal uterine bleeding
Feature
Normal
Abnormality 1
Abnormality 2
Regularity
Regular ±2;20d
Iregular variation > 20d
Absent
Frequency
Normal q 24-38d
Frequent < 24d
Infrequent >38d
Duration
Normal 4,5-8d
Prolonged > 8d
Shortened <4,5d
Volume
Heavy
Light 23

24. Classification of causes of abnormal uterine bleeding
PALM - COEIN
Polyp
Coagulopathy
Adenomyosis
Ovulatory dysfunction
Leiomyoma
Submucosal
Endometrial
Other
Iatrogenic
Malignancy&hyperplasia
Not classified
Thesystem ha sbeen approved by the FIGO Executiv eBoardas aFIGO classification system.
There are 9 main categories,which are arranged according to the acronym PALM-COEIN(pronounced“pahm-koin”): 24

25. Myoma classification Submucosal Pedunculated intracavitary 1
Pedunculated intracavitary 1
>50% intracavitary 2
≤50% intracavitary
Other 3
Contacts endometrium, 0% intracavitary 4
Intramural 5
Subserosal ≥50% intramural 6
Subserosal <50% intramural 7
Subserosal pedunculated 8

26. Initial evaluation. For a diagnosis of chronic abnormal uterine bleeding (AUB), the initial assessment requires the patient to have experienced 1 or a combination of unpredictability, excessive duration, abnormal volume, or abnormal frequency of menses for at least the previous 3 months. Patients should undergo a structured history designed to determine ovulatory function, potential related medical disorders, medications, and lifestyle factors that might contribute to AUB. For those with heavy menstrual bleeding, the structured history should include the questions from Table 1 . Understanding the future fertility desires of the patient will help to frame the discussion of therapy following appropriate investigation. Ancillary investigations should include a hemoglobin and/or a hematocrit assessment, appropriate tests for features that could contribute to an ovulatory disorder (thyroid function, prolactin, and serum androgens), and if the Table 1 -based structured history is positive for coagulopathy either referral to a hematologist or appropriate tests for von Willebrand disease. Reproduced, with permission, from Ref. [11] .
Reproduced, with permission, from Ref. [11] .
FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age
Munro, Malcolm G., International Journal of Gynecology & Obstetrics, Volume 113, Issue 1, 3-13
Copyright © 2011

27. Uterine evaluation. The uterine evaluation is, in part, guided by the history and other elements of the clinical situation, such as patient age, presence of an apparent chronic ovulatory disorder, or presence of other risk factors for endometrial hyperplasia or malignancy. For those at increased risk, endometrial biopsy is probably warranted. If there is a risk of structural anomaly, particularly if previous medical therapy has been unsuccessful, evaluation of the uterus should include imaging, at least with a “screening” transvaginal ultrasound (TVUS) examination. Unless the ultrasound image indicates a normal endometrial cavity, it will be necessary to use either or both hysteroscopy and saline infusion sonography (SIS) to determine whether target lesions are present. Such an approach is also desirable if endometrial sampling has not provided an adequate specimen. Uncommonly, these measures are inconclusive or, in the instance of virginal girls and women, not feasible outside of an anesthetized environment. In these instances, magnetic resonance imaging (MRI) may be of value, if available. Abbreviations: AUB, abnormal uterine bleeding; CA, carcinoma. Reproduced, with permission, from Ref. [11] .
Reproduced, with permission, from Ref. [11] .
FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age
Munro, Malcolm G., International Journal of Gynecology & Obstetrics, Volume 113, Issue 1, 3-13
Copyright © 2011

28. Menstrual cycle disorders
Polymenorrhoea
Oligomenorrhoea
Hypomenorrhoea
Amenorrhoea
Menorrhagia
Hypermenorrhoea
Dysmenorrhoea
Premenstrual syndrome 28

29. Polymenorrhoea vs. oligomenorrhoea

30. Hypermenorrhoea vs. menorrhagia30

31. Dysmenorrhoea Painful menstruation
Primary – occurs only in ovulatory cycles
High level of prostaglandines
Secondary
Endometriosis
Pelvic inflammatory disease
Congenital abnormalities 31

32. Premenstrual syndrome
Complex of physical and emotional symptoms that occur cyclic before menstruation
Therapy - symptomatic
Premenstrual syndrome (PMS), also known as premenstrual tension, is a
complex of physical and emotional symptoms that occur repetitively in a
cyclic fashion before menstruation and that diminish or disappear with
menstruation. 32

33. …thank you for your attention