The menstrual cycle is regulated by hormones from the hypothalamus, pituitary, and ovaries. It involves two cycles - the ovarian cycle which includes the follicular, ovulatory, and luteal phases, and the endometrial cycle which includes the proliferative, secretory, and menstrual phases. Common menstrual disorders include premenstrual syndrome, mastodynia, and abnormal uterine bleeding such as menorrhagia, metrorrhagia, and amenorrhea. Diagnosis involves taking a medical history and performing examinations, scans, and biopsies to determine the underlying cause.
2. OUTLINE
INTRODUCTION
REGULATION OF THE MENSTRUAL CYCLE
OVARIAN CYCLE
ENDOMETRIAL CYCLE
MENSTRUATION
SOME CLINICAL SIGNIFICANCE OF THE
MENSTRUAL CYCLE
DISORDERS OF THE MENSTRUAL CYCLE
CONCLUSION
REFERENCES
3. INTRODUCTION
The menstrual cycle is the regular natural changes that occur
in the ovaries and uterus that makes pregnancy possible.
It occurs due to the rise and fall of hormones in the cycle.
4. INTRODUCTION CONT’D
Definition of normal menstruation
It is the cyclical shading of a functional endometrium; and has the following
characteristics:
Amount of flow: 25-80 ml average 30 mls
Cycle length: 21-35 days
Duration of flow: 2-7 days
Healthy menstrual blood does NOT coagulate
It occurs in a cyclic manner and regularly
5. INTRODUCTION CONT’D
Menstruation is the visible manifestation of cyclic physiologic
uterine bleeding due to shedding of the endometrium following
interplay of hormones mainly through hypothalamo-pituitary-
ovarian axis.
For menstruation to occur, the axis must be actively coordinated,
endometrium must be responsive to the ovarian hormones and
the outflow tract must be patent.
6. INTRODUCTION CONT’D
Since menstruation is the obvious monthly event during the
reproductive life, it is termed the “menstrual cycle”
However, the normal menstrual cycle is mostly a reflection of
ovarian events.
7. Regular menstruation is the obvious marker that the various level of
interaction of the hypothalamus, pituitary, ovary and uterus are
functionally intact.
The main aim of the menstrual cycle is to ensure mono ovulation,
and implantation of an early embryo can arrest the process of
endometrial shedding and ensure its survival.
INTRODUCTION CONT’D
8. REGULATION OF THE MENSTRUAL CYCLE
The menstrual cycle is regulated at both endocrine and
paracrine levels.
Endocrinologically there are classical feedback loops that
modulate release of gonadotropin hormones from the
pituitary with the ovarian steroids as the afferent arm.
More recent studies have begun to elaborate a complex
series of paracrine processes that operate within the
tissues of the ovary and uterus to impose local
regulation.
9. REGULATION OF THE MENSTRUAL
CYCLE CONT’D
The hypothalamus in the forebrain secretes the peptide hormone;
gonadotropin-releasing hormone (GnRH).
This in turn controls pituitary hormone secretion.
GnRH is released in a pulsatile fashion to stimulate pituitary secretion of
Luteinizing hormone (LH) and Follicle-stimulating hormone (FSH).
11. The physiology of the menstrual
cycle can be conveniently divided
into:
ovarian cycle
endometrial cycle.
12. THE OVARIAN CYCLE
The functional and morphological changes that occur in the ovarian
follicle during the menstrual cycle can be divided into 3 phases.
1. Follicular phase
2. Ovulatory phase
3. Luteal phase
13. Follicular phase
The initial stage of follicular development is independent of hormonal
stimulation (at the pre-antral stage).
Development beyond the pre-antral stage is stimulated by the
gonadotropins (LH & FSH).
At the beginning of the menstrual cycle there is a rising level of FSH
which rescue a cohort of follicle from atresia and initiates
steroidogenesis.
14. Ovarian steroidogenesis is described as the two cell, two
gonadotropins hypothesis which states that the theca and granulosa
cells are responsive to LH & FSH respectively.
The androgens produced by the theca cells are converted to estrogen
by the granulosa cells.
Follicular phase
15. Of the rescued cohort of pre-antral follicle, only
one of these grow into a pre-ovulatory follicle
called the dominant follicle.
The dominant follicle is the largest follicle with
the most efficient aromatase activity, highest
concentration of FSH-induced LH receptors,
produce the greatest amount of oestradiol and
requires the lowest level of FSH for continued
development.
Follicular phase
16. Ovulatory phase
Late in the follicular phase as the dominant
follicle develops, follicular production of
oestrogen increases to the threshold required to
exert a positive feedback effect on the pituitary
LH secretion.
Increased secretion of LH leads to leutinization
of the granulosa cells and subsequent
production of progesterone which further
amplifies the positive feedback effect of
17. Ovulation occurs 36hrs after the onset of the LH surge.
In addition, the LH surge stimulates follicular expression
of macrophage chemotactic protein-1 (MCP-1) and
interleukin-8 (IL-8) which causes influx of macrophages
and neutrophils into the pre-ovulatory follicle.
These leukocytes secrete matrix, metalloproteases and
prostaglandin which causes a break down of the follicle
wall releasing the oocyte at ovulation.
Ovulatory phase
18. Luteal phase
The ruptured follicle at the time of ovulation
then fills with blood (corpus hemorrghagicum)
The granulosa and theca cells of the follicle
begin to proliferate and the clotted blood is
rapidly replaced with a yellowish, lipid rich
luteal cells forming the corpus luteum.
The luteal cells secrete estrogen and
predominantly progesterone
19. If the ovum is fertilized and pregnancy occurs,
the corpus luteum persist and maintains the
pregnancy.
If fertilization does not occur, the corpus
luteum degenerate about 4days before the
next menstruation and is eventually replaced
by fibrous tissue forming corpus albicans.
Luteal phase
20. THE ENDOMETRIAL CYCLE
Under the influence of ovarian hormones produced in
the ovarian cycle described above, the endometrium
undergoes cyclical changes which can be divided into
3 phases
1. Proliferative phase
2. Secretory phase
3. Menstrual phase
21. Proliferative phase
Under the influence of oestrogen, the epithelial lining and
glands changes from a single layer of low columnar cells to
pseudostratified columnar epithelium with frequent mitosis.
The stromal component of the endometrium re-expands and
is infiltrated by bone marrow derived cells.
The massive development is reflected in the increase in
endometrial thickness, from 0.5mm at menstruation to 3.5-
5mm at the end of the proliferative phase.
22. Secretory phase
This is the post ovulatory phase of the menstrual
cycle and is characterised by endometrial glandular
activity.
The changes in this phase is as a result of the action
of oestrogen and predominantly progesterone on a
previously oestrogen primed endometrium.
The glands continue to grow, leading to the
tortuosity of the glands and spiral arteries.
23. Vacoule containing subnuclear intracytoplasmic
granules appear in the glandular cells which
progress to the apex of the cells and there content
released into the endometrial cavity.
The peak secretory activity occurs at the 7th day after
LH surge.
Secretory phase
24. Menstruation
Menstruation is initiated by a fall in the
circulatory concentration of progesterone that
follows luteal regression.
Withdrawal of progesterone causes
vasoconstriction of the spiral artery, however
the vasoconstriction effect of progesterone is
indirect but generated by locally produced
prostaglandins, endothelin and angiotensin II.
25. These agents attract and activate macrophages and
neutrophils into the endometrium.
Both invading leukocytes and endometrial stromal
cells then releases and activates matrix
metalloproteases (MMPs) which break down
extracellular matrix.
26. The tissue hypoxia caused by the vasoconstiction
of the spiral artery leads to production of vascular
endothelial growth factor (VEGF) which stimulate
angiogenesis.
The above events leads to ischaemia and tissue
damage, shedding of the functional layer of the
endometrium (stratum compactum and stratum
spongiosum) and bleeding from fragments of
arterioles remaining in the basal endometrium.
27. Progesterone withdrawal also leads to the
production of pro-inflammatory cytokines such as
macrophage chemotactic protein-1 (MCP-1), IL-8
and cyclo-oxygenase-2
Menstruation ceases as the damaged spiral arteries
begin to vasoconstrict and the endothelium
regenerates
These vasoconstriction and increased fibrinolysis
minimize scaring to maintain the function of the
endometrium
28. The repair involves both glandular and stromal
regeneration and angiogenesis mediated by
angiogenic agents such as VEGF and fibroblast
growth factor in the endometrium
The repair of the endometrium leads to complete
ceasation of bleeding within 5-7days from the start
of menstruaton.
30. CLINICAL SIGNIFICANCE OF THE
MENSTRUAL CYCLE
Disorders that slow GnRH pulsatility, such as
anorexia in failure of secretion of pituitary
gonadotropin and state if
hypogonadotrophic hypogonadism, with
undetectable serum LH and FSH and
amenorrhea.
31. CONT’D
The peptide kisspeptin acts as a potent
stimulant to GnRH secretion in human and
mutations in the KISS 1 gene leading to
kisspeptin signaling have been identified as
rare causes of hypogonadotrophic
hypogonadism.
32. CONT’D
Central kisspeptin release is also modulated
by stress and nutritional status, providing a
possible mechanism for ‘hypothalamic’
amenorrhoea in anorexia and in situations of
excessive emotional stress.
33. CONT’D
The LH surge is also preceeded by a rise in serum
concentration of progesterone.
The contribution of this rise to the peri-ovulatory
phase of the cycle is unclear, but prevention of
the pre-ovulatory rise in serum progesterone
concentration using progesrerone receptor
antagonists such as mifepristone prevents
efficient ovulation
34. CONT’D
The clinical relevance of the positive feedback
of oestrogen on the periovulatory LH surge is
seen in the use of the combined oral
contraceptive pill, which artificially creates a
constant serum oestrogen level in the
negative feedback range, inducing a
corresponding low level of gonadotropin
hormone release.
35. Classification of menstrual
disorders
Premenstrual syndrome (PMS)
Mastodynia
Abnormal bleeding due to gynecologic and non
gynecologic disorders:
Amenorrhea, oligomenorhea, hypomenorrhea,
menorrhagia, polymenorrhea, metrorrhagia, etc
Dysmenorrhoea
Dysfunctional uterine bleeding (DUB)
Post menopausal bleeding
37. Premenstrual syndrome:
occurs in at least 3 consecutive menstrual cycles
Symptoms must occur in the 2nd half of the menstrual cycle (luteal phase)
There must be a symptom free period of at least 7 days in the 1st half of the
cycle
Symptoms must be severe enough to require medical advise or treatment
e.g. oedema, weight gain, restlessness, irritability and increased tension.
39. PMS -Diagnosis
Mainly based on patient’s history
Patient charts symptoms for at least 3 symptomatic cycles
Rule out medical conditions that mimic PMS e.g. thyroid disease and
anemia.
41. PMS management
(Drug therapy)
Calcium carbonate (for bloating, pain and food cravings)
Magnesium ( for water retention)
Vitamin B6 and vitamin E
NSAIDs
Bromocryptine for mastalgia
42. Mastodynia
Also termed mastalgia
Defined as: intolerable breast pain during the second half of the menstrual
cycle.
caused by edema and engorgement of the vascular and ductal systems
Occurs cyclically in the luteal phase
43. Mastodynia -diagnosis
History and examination
Can be confirmed by aspiration
Ultrasound
Serial mammography
Excisional biopsy sometimes is necessary
Rule out: Mastitis, neoplasm
44. Mastodynia- treatment
Breast support
Avoid- coffee, tea, chocolate, cola drinks
Avoid nicotine
May occasionally use a mild diuretic
Drug therapy: topical NSAIDS, Gosarelin (Zoladex),
Limited success with: tamoxifen, danazol, bromocryptine, oral
contraceptives, vitamins
45. Menorrhagia (Hypermenorrhea)
Defined as excessive, heavy or prolonged menstrual flow
Possible causes include: submucous myomas, adenomyosis,
IUDs, endometrial hyperplasia, malignant tumors e.t.c
46. Hypomenorrhea
(cryptomenorrhea)
Defined as unusually light menstrual flow sometimes only
spotting
Possible causes include: hymenal or cervical stenosis,
uterine synechiae (Asherman’s syndrome), occasionally oral
contraceptives
47. Metrorrhagia (intermenstrual bleeding)
Defined as bleeding occurring any time between the menstrual periods
Possible causes include: endometrial polyps, CA cervix, CA endometrium,
exogenous estrogen administration
48. Polymenorrhea
Describes periods that occur too frequently
Usually associated with anovulation and rarely with a
shortened luteal phase in the menstrual cycle
49. Menometrorhagia
This is bleeding that occurs at irregular intervals and varies
in amount and duration of bleeding
Caused by any condition that can lead to intermenstrual
bleeding
50. Oligomenorrhea
Describes menstrual periods that occur more than 35 days
apart
Possible causes: anovulation which may be from endocrine
causes (pregnancy, menopause, pituitary and hypothalamic
disorders); or systemic causes (excessive weight loss);
estrogen secreting tumors etc
51. AMENORRHEA
No menstrual period for more than 6 months
Possible causes:
- Congenital uterine absence
- Hormonal disturbances from the hypothalamus and pituitary gland
- Failure of the ovary to receive or maintain egg cells
- Genetic diseases e.g. causes of intersex i.e. 5-alpha-reductase deficiency
52. Diagnosis in abnormal uterine
bleeding
History and physical examination
Cytological examination –include biopsy
and histology
Pelvic ultrasound scan
Endometrial biopsy
Hysteroscopy
Dilatation and curettage
Hormonal profile
Blood tests- Haemogram, thyroid function
tests e.t.c.
53. Management of abnormal uterine
bleeding- principles
Treat cause appropriately
May include
Hormonal preparations
Surgery
Endometrial ablation and endometrial resection,
Prostaglandin synthetase inhibitors,
Levonogestrel releasing IUDs
54. Dysmenorrhea
Definition: Pain associated with menstruation
Risk factors:
Menstrual factors (early menarche, menorrhagia)
Parity (lower in multipara)
Diet (reduced intake of fish, eggs and fruits)
Exercise (reduces dysmenorrhoea)
Cigarette smoking (increases)
Psychological (emotionally dependent and
overprotected girls, family history,)
55. Dysmenorrhea- classification
Primary or spasmodic dysmenorrhea:
Essential/ intrinsic / functional. Defined as painful menstruation
in absence of pelvic pathology
Usually starts at puberty
Follows onset of ovulation and presents throughout period of
bleeding.
Congestive or secondary dysmenorrhea:
Underlying pelvic disease e.g. uterine abnormalities, infections,
endometriosis, foreign bodies, iatrogenic
Membranous dysmenorrhea:
associated with passage of endometrial cast through an undilated
cervix.
56. Dysmenorhea- clinical features
Primary Dysmenorhea:
Age: Usually seen among younger women
Time of onset: 2-3 yrs after menarche
Duration of pain: starts just prior to menses, lasts about 2 days
Type of pain: cramping pain
Membranous Dysmenorhea:
Intense cramping pain associated with passage of an endometrial cast through
an undilated cervix.
57. Dysmenorhea- clinical features (ctd)
Secondary Dysmenorhea:
- Associated with specific diseases and disorders e.g.
PID, Uterine fibroids, endometriosis etc
Usually among older women (3rd to 4th decade)
Time of onset: follows initial years of normal painless cycles
Duration of pain: Onset is few days prior to menses and continues throughout
cycle even after cessation of menses
Type of pain: continuous dull aching or dragging pain
58. Dysmenorhea -management
Dysmenorhea
Assurance
Laxatives
Analgesics and Antispasmodics
Fails
Contraception not required or OC pills
contraindicated
Contraception required or NSAIDS contra
indicated
Prostaglandin synthetase inhibitors OC pills
Fails
Laparoscopy to look for causes of secondary Dysmenorhea
No cause found but persistent and
severe pain
Cause found
Surgery Treat as appropriate
59. Dysfunctional Uterine bleeding
(DUB)
Defined as a symptom complex that includes any condition of abnormal
uterine bleeding in the absence of pathologic cause
Commonly caused by anovulation as seen in polycystic ovarian disease and
obesity
May occur in all age groups from prepubertal girls to menopausal women
61. Postmenopausal bleeding
Any vaginal bleeding in a postmenopausal women should be
considered abnormal
Frequently associated with malignancies of the reproductive
tract
Benign causes include: endometrial /cervical polyps, trauma,
senile vaginitis, vulval dystrophies
Management depends on the cause.
62. AUB
Normal menstrual cycle involves hypothalamus-
pituitary-ovary and uterus and is 28 days
Vaginal bleeding is abnormal (Abnormal Uterine
Bleeding--AUB) when:
Volume is excessive or
Occurs at times other than expected, including during
pregnancy or menopause
Known as dysfunctional uterine bleeding (DUB) when
organic causes are excluded
63. AUB
Duration >7 days or
Flow >80ml/cycle or
Occurs more frequently than 21 days or
Occurs more than 90 days apart or
Intermenstrual or postcoital bleeding
69. Hematologic
Von Willebrand’s disease (most common inherited
bleeding disorder with frequency 1/800-1000)
Hemophilia
Thrombocytopenia
Hematologic malignancies (leukemia)
Liver disease
70. Other
DUB (dysfunctional uterine bleeding): non-
organic causes, either ovulatory or
anovulatory
Fallopian tube cancer
Trauma
Foreign body
Cervical bleeding--mets, cervicitis, cervical
cancer
Vaginitis--atrophic, cancer of vagina
Endometrial cancer (10% of post-menopausal
bleeding)
71. Evaluation of Abnormal
Uterine Bleeding (AUB)
Acute
History suggestive of:
Pregnancy and
related
complications
Recent and Heavy
bleeding
Pelvic pain
Medications
contributing to
above
Chronic
History:
Long standing abnormal
menstrual history
Symptoms of anemia,
hypothyroidism,
perimenopause
Personal or family history of
excessive bleeding
72. AUB Examination
Assess vitals/hemodynamic stability
Look for features of anemia (pallor, tachycardia,
syncope)
Look for features of hypothyroidism
Look for metabolic syndrome (obesity, hirsutism, acne)
Pelvic exam for structural abnormalities: fibroids,
pregnancy, active bleeding—uterine vs. cervical
bleeding
73. AUB Lab Studies
Serum HCG to rule out pregnancy
CBC and iron studies to assess severity of anemia
TSH for thyroid disorders
Coagulation studies (PT, PTT, platelet count, VWF)
(primarily for adolescents)
Transvaginal ultrasound to look for fibroids and other
masses/lesions
Endometrial biopsy to rule out endometrial cancer in
perimenopausal and chronic anovulatory cycles
(primarily for women >35 years with AUB and
postmenopausal women)
Sonohysterography is useful in diagnosis of anatomical
lesions which might even be missed with transvaginal
ultrasound
74. Treatment of Chronic
Menorrhagia for Most Causes
(including DUB)
Combined hormonal contraceptives (cyclical or
continuous)
DMPA (depot medroxyprogesterone)
IUD (Intrauterine devices)
75. Treatment options continued
After excluding coagulopathy, pregnancy, or malignancy:
Progestins
Estrogens including oral contraceptives
Cyclic NSAIDS
Dilatation and curettage (surgical)
Endometrial ablation (surgical)
Hysteroscopic endometrial resection (surgical)
76. Treatment for Fibroids
Surgical: Hysterectomy/myomectomy, uterine artery
ablation
Medical: Suppression of gonadotropins (danazol and
leuprolide)
77. Treatment: progestins
Inhibits endometrial growth by inhibiting synthesis of
estrogen receptors, promotes conversion of estradiol
to estrone, inhibits LH
Organized slough to basalis layer
Stimulates arachidonic acid production
Progestins preferred for those women with
anovulatory AUB
78. Progestational Agents
Cyclic medroxyprogesterone 2.5-10mg daily for 10-14
days
Continuous medroxyprogesterone 2.5-5mg daily
DMPA 150 mg IM every 3 months
Levonorgestrel IUD (5 years)
79. Estrogens
Conjugated estrogens given IV every 6 hours effective
in controlling heavy bleeding followed by oral
estrogen
For less severe bleeding, oral conjugated estrogens
1.25 mg, 2 tabs qid--until bleeding stops
80. NSAIDS
Cyclooxygenase pathway is blocked
Arachidonic acid conversion from prostaglandins to
thromboxane and prostacyclin (which promotes
bleeding by causing vasodilation and platelet
aggregation) is blocked
81. Clinical Highlights
Most common cause of AUB in reproductive age is
pregnancy related--so initial evaluation must include
pregnancy test.
Pregnancy must be ruled out before initiating invasive
testes or medical therapy
82. Clinical Highlights
Endometrial biopsy is recommended for post
menopausal women
Or
Younger women with history of chronic anovulation
>35 years of age
83. Clinical Highlights
Uterine cancer and endometrial hyperplasia must be
ruled out before medical therapy is initiated in
postmenopausal/perimenopausal bleeding
NSAIDS may reduce menstrual flow by 20-60% in
women with chronic menorrhagia
Coagulopathy workup must be initiated in
menorrhagia in adolescents
84. CONCLUSION
Although the events that regulate the ovarian and
endometrial cycles are complex, a clear understanding
of the basic physiology of the cycle will improve the
management of menstrual disorders.
85. REFERENCES
Gynaecology by ten teachers
Textbook of obstetrics and gynaecology, Akin
Agboola
Current Diagnosis and treatment, obstetrics
and gynaecology, Alan et al.
Dewhust’s textbook of obstetrics and
gynaecology, D. Keith Edmonds.
86. FERENCES
ACOG Practice Bulletin #14, 2000
American Journal Obstetrics and Gynecol
2005;193:1361
Clinical Obstetrics & Gynecology 50(2):324-353, June
2007
Comprehensive Gynecology, 4th edition
Harrison’s Principles of Internal Medicine, 14th edition
Karlsson, et al, 1995