1.2 The Menstrual Cycle

Question 1

The menstrual phase (days 1 – 4) occurs with the shedding of the _____________ (stratum basalis remains intact → allows for endometrial regeneration):
• Occurs when there is no fertilisation or implantation of the ovum in the endometrium → corpus luteum involutes → decreased oestrogen and progesterone
• Decreased hormones causes constriction of ________________ → necrosis

Answer 1

stratum functionalis;

endometrial spiral arteries

Question 2

The ovarian follicular/endometrial proliferative phase (days ________) occurs with the pulsatile release of GnRH from the hypothalamus:
• Pituitary gland gonadotrophs release LH and FSH → triggers ______________ → follicles secrete oestradiol
• Oestradiol has negative feedback on FSH/LH (at first) then positive feedback on both (midcycle; preparing for ovulation surge), regeneration of endometrium (within 3 days of cessation of menstrual flow)
o Involves proliferation of __________, elongation of ________, proliferation of _________________
• Lower basal body temperature

Answer 2

5 – 13;

follicular growth (in ovary);

stromal cells;

glands;

spiral arteries into stroma

Question 3

Ovulation (day 14) occurs due to an __________ (due to positive feedback on the hypothalamus and anterior pituitary exerted by oestradiol):
• Rupture of the dominant (Graafian) follicle (24 – 36 hours after LH surge) releases the ovum into the peritoneal cavity → picked up by the ________________
• Travel towards the uterine cavity (fertilisation often occurs in the tube)

1. Following ovulation, FSH and LH causes the dominant follicle to transform into the corpus luteum
2. During the secretory phase, the endometrium transforms itself due to the secretion of ______________ by the corpus luteum and attains the full maturity.
   - glands and arteries begin to become entwined
   - endometrial connective tissue stroma becomes oedematous
3. this is the optimal time for implantation for the fertilised oocyte.
4. as the corpus luteum degenerates, the progesterone levels fall and menstruation occurs.

Answer 3

abrupt surge of LH;

fimbriae of Fallopian tubes;

progesterone;

Question 4

What happens if fertilisation is absent during ovarian luteal/endometrial secretory phase (days 14 – 28)?

Answer 4

Corpus luteum involutes (after ~7 days) → oestrogen and progesterone fall → menstruation

Question 5

What happens if fertilisation is present during ovarian luteal/endometrial secretory phase (days 14 – 28)?

Answer 5

LH maintains the corpus luteum until the implanted embryo makes human chorionic gonadotrophin (hCG) → maintains corpus luteum and progesterone production

Question 6

What are the structural causes (PALM) if menorrhagia?

Answer 6

Polyps, adenomyosis, leiomyoma (fibroids), malignancies/hyperplasia
• Fibroids may occur in different parts of uterus (e.g. subserosal, intramural, submucosal, avulsing fibroid polyp, intraligamental)

Question 7

What are the non structural causes (COEIN) if menorrhagia?

Answer 7

Coagulopathy, ovulatory dysfunction, endometrial, iatrogenic, not yet classified

Question 8

What is the definition of menorrhagia?

Answer 8

Menorrhagia (heavy menstrual bleeding) is defined as blood loss considered excessive by the woman and interferes with physical, emotional, social, material quality of life:
• Conventionally defined as > 80mL/cycle (subjective → may be normal for some)

Question 9

Anovulatory AUB results from absent ovulation → no formation of the corpus luteum → insufficient effects of progestogens on the endometrium:
• Caused by abnormalities of production of _______________
• Results in unopposed ___________ effects → increased and persistently proliferatively endometrium (very vascular → irregular painless bleeding)
• Anovulatory cycles are common at menarche (with irregular period) and menopause (associated with heavy erratic bleeding) → most commonly due to _______

Answer 9

oduprostanoids and steroid receptors;

oestrogen ;

PCOS

Question 10

what is the definition of post menopausla bleeding?

Answer 10

PMB is defined as any vaginal bleeding > 1 year after the last period.

Question 11

what is the definition of intermenstrual bleeding?

Answer 11

any uterine bleeding between regular menstruation which may be possibly physiological (due to sharp rises and falls of oestrogen at ovulation)

Question 12

what are the causes of intermenstrual bleeding?

Answer 12

Common causes: polyps (cervical/endometrial), cervical ectropion (protrusion of columnar epithelium through the external os)
o Endocervical polyps are almost always benign → cutting it (avulsion) is a common way to remove and treat it

• Rare causes: cervical cancer

Question 13

what is post coital bleeding?

Answer 13

PCB is any non-menstrual bleeding at the time of/shortly after sexual intercourse

Question 14

What is the definition of dysmenorrhea?

Answer 14

painful menstruation and abdominal cramps (common in adolescence and occurs only in ovulatory cycles):

Question 15

What are the causes of primary dysmenorrhoea?

Answer 15

• Uterine contractions and transient ischaemia of uterine muscle (due to decreased endometrial blood flow during menstruation)
• Higher levels of prostaglandin F2α and E2 in the menstrual blood (vasoconstrictive and stimulant to the myometrium) → administration causes dysmenorrhoea-like pain
• Increased leukotrienes (produced by endometrium) which increases contractility of the myometrial muscle fibres
• Increased vasopressin release in the plasma (stimulate myometrial contractions in the non-pregnant uterus)

Question 16

What are the causes of secondary dysmenorrhea?

Answer 16

Secondary dysmenorrhoea occurs due to the presence of an underlying disease:

• endometriosis
• adenomyosis
• PID
• pelvic venous congestion
• cervical stenosis (use of IUD)

Question 17

What is endometriosis?

Answer 17

Ectopic endometrial tissue outside the uterine cavity causing a chronic inflammatory reaction:

Question 18

Where are the common sites of endometriosis?

Answer 18

peritoneal surface, appendix, bowel (common), lungs, brain (rare), ovary (endometrioma/chocolate cyst)

Question 19

What are the symptoms of endometriosis?

Answer 19

infertility (with pelvic scarring), impaired bladder and bowel function (severe cases)

Question 20

What is adenomyosis?

Answer 20

Deposits of endometrial tissue within the myometrium (may be visible as blue spots on the uterus in laparoscopy):
• Adenomyoma: localised collection

Question 21

What are the symptoms of adenomyosis?

Answer 21

dysmenorrhoea, HMB

Question 22

What is PID?

Answer 22

Any upper genital tract infection (commonly caused by STIs in the developed world like chlamydia and gonorrhoea)
• May also be caused by pelvic surgery
• Causes scarring → pain and infertility

Question 23

What is pelvic venous congestion?

Answer 23

Enlarged varicose veins within the pelvis → chronic pelvic pain

Question 24

What is cervical stenosis?

Answer 24

Narrowing or complete closure of cervical os (commonly secondary to scarring due to surgery/treatment of cervix e.g. loop excision for cervical intra-epithelial neoplasia/CIN)

Question 25

What is oligomenorrhea?

Answer 25

infrequent menstrual cycles lasting more than 35 days.

Question 26

What is the definition of primary ammenorrhea?

Answer 26

Failure to start menstruation by 16 years of age or absence of secondary sexual characteristics by 14 years of age

Question 27

What is the definition of secondary amenorrhea?

Answer 27

Menstruation stops for > 6 months in non-menopausal (previously menstruating) women or for 3 cycles in women with longer/irregular periods:

Question 28

What are the hypothalamic causes of amenorrhea?

Answer 28

• Hypothalamic hypogonadism (Decreased GnRH → decreased FSH/LH → decreased oestrogen/progesterone)
• High stress, low BMI (Occurs in eating disorders or very athletic women (normal menstruation is unlikely with BMI < 19kg/m2))
• Kallman syndrome ( Failure of development of GnRH neurones → primary amenorrhoea and failure of development of secondary sexual characteristics:)
  • Associated with hyposmia/anosmia, colour blindness, unilateral renal agenesis/aplasia

Question 29

What are the pituitary causes that cause amenorrhea?

Answer 29

Pituitary adenoma/ hyperlasia: hyperprolactinaemia (due to lack of dopamine inhibition from pituitary stalk compression or excessive production from prolactinomas):
• Stimulates release of dopamine (from hypothalamus) → reduces GnRH → reduces FSH/LH secretion
• Causes anovulation and amenorrhoea

Sheehan’s syndrome: Pituitary gland necrosis (following childbirth) due to ischaemic necrosis from massive blood loss and hypovolaemic shock:
• Low hypophyseal portal venous pressure normally supplies the anterior pituitary → overall increased blood supply during pregnancy causes the pituitary gland to become especially sensitive to sudden drops in BP
• Causes amenorrhoea, lactation failure, secondary adrenal insufficiency, hypothyroidism

Question 30

What are ovarian disorders that can cause amennorhea?

Answer 30

• ovarian dysgenesis (Primary ovarian failure with absence of ovarian oocytes and follicles) : Turner’s syndrome, 46XX gonadal dysgenesis, 46XY gonadal dysgenesis (rare)
• PCOS: Occurs due to elevated androgens in females (onset 10s – 20s):
• premature ovarian failure (syndrome, autoimmune oophoritis, chemotherapy/radiotherapy-induced ovarian failure, fragile X permutation carriers)

Question 31

Why does 45XO cause amennorhea?

Answer 31

Ovaries become replaced with fibrous tissue (streak ovaries) which do not produce much oestrogen:

Question 32

What are the symptoms of 45XO?

Answer 32

• External female genitalia, uterus, and Fallopian tubes develop normally until puberty (oestrogen-induced maturation fails to occur)
• Pubarche (adrenal-mediated pubic hair development) tends to occur before thelarche (if it occurs at all → ovary-mediated)
• Patients with mosaic karyotype (some cells 45X, some 46XX) may have spontaneous menstruation and pregnancy

Question 33

What is the treatment of 45 XO?

Answer 33

hormone replacement therapy (oestrogen), growth hormone with low dose androgen (if young → for boosting growth)

Question 34

what are the symptoms of PCOS?

Answer 34

Triad of symptoms (PCOS): oligomenorrhoea (with anovulatory cycles), polycystic appearance (enlarged ovary containing numerous small follicles on the outer edge), abnormal secondary sex characteristics (hirsutism, acne, weight gain → high virilising hormones but low virilising hormone binding globulins)

Associated with high levels of insulin + insulin resistance and increased lifetime risk of CVD and diabetes (metabolic syndrome)

Question 35

What are structural genital tract disorders that cause amennorhea

Answer 35

• absense of uterus( MRKH syndrome associated with unilateral renal agensis/ dysplasia and skeletal malformations)
• Imperforate hymen / Transverse vaginal septum (Blocks the outflow of menstrual blood)
• Asherman’s syndrome ( Trauma to the basal layer of the endometrium occurring due to evacuation of the uterus (often after dilation & curettage post-miscarriage, delivery, termination))

Question 36

What are the receptors disorders that can lead to ammenorhea?

Answer 36

Complete androgen insensitivity syndrome (AIS) is an X-linked recessive disorder causing a defective androgen receptor → genetically 46XY individuals are testosterone-resistant:
• Possesses the appearance of a normal woman (even though they are genetically male) and do not develop testosterone-dependent male sexual characteristics

Question 37

How does Complete androgen insensitivity syndrome (AIS) presents at puberty?

Answer 37

breast development, but pale areola, sparse axillary hair → testes may be palpable in the labia or inguinal area

Mullerian inhibiting substance (MIS) produced by the testes is functional and causes regression of Mullerian structures (internal genitalia: Fallopian tubes, uterus, upper third of vagina)

Question 38

what are enzymes deficiencies that can cause ammenorhea?

Answer 38

Mullerian inhibiting substance (MIS) produced by the testes is functional and causes regression of Mullerian structures (internal genitalia: Fallopian tubes, uterus, upper third of vagina)

Question 39

How does Congenital 5α-reductase deficiency presents at puberty?

Answer 39

virilisation occurs due to normal peripubertal increase in testosterone → DHT-dependent masculinisation (e.g. enlargement of male external genitalia and prostate) fails to occur
• Testosterone-dependent pathways are intact → male pattern hair growth, muscle mass, deepening of voice

Question 40

what are medically induced causes of ammenorhea?

Answer 40

Natural/synthetic steroid hormones (e.g. progesterone) which help to maintain pregnancy and prevent further ovulation during pregnancy:
• Suppression of ovulation: corpus luteum fails to develop → decreased progesterone production
• Decreased endometrial proliferation → eventual cessation of menstruation

GnRH analogues ( Produces similar effects to intrinsic GnRH → continuous administration (usually via depot IM injection) → increased FSH/LH → pituitary gland desensitisation after about 10 days → suppression of FSH/LH → inhibition of ovarian steroidogenesis)

Radiotherapy/ chemotherapy ( Treatment of malignancies → permanent damage to the gonads (degree depends on dose, age, prior peri/postmenopausal status))