The menstrual cycle

What happens during the follicular phase (pre-ovulatory)?

Primary oocyte = frozen at prophase 1

Primary follicle: primary oocyte surrounded by granulosa cells + theca cells → release oestrogen

Early secondary follicle: surrounded by zona pellucida (glycoprotein membrane) → produce oestrogen

Late secondary follicle: same as early secondary follicle with pockets of fluid containing hyaluronic acid

Graafian follicle:

• primary oocyte → secondary oocyte (frozen at Metaphase II)

• surrounded by corona radiata (cells differentiated from granulosa cells)

• Pockets of fluid combine to form the antrum 

How is the follicular phase initiated?

Hypothalamus → GnRH → ant pituitary →

FHS  → granulosa cells → androgens to oestrogen

 LH → theca cells → cholesterol to androgens

** 2-cell, 2-gonadotrophin hypothesis

What feedback mechanism is in place during the mid follicular phase?

Levels of oestrogen slowly increase → negative feedback to ant pituatry → LH + FSH decrease (to not make more follicles mature)

What feedback mechanism is in place during the late follicular phase?

 Graafian cells produce inhibin to stop FSH secretion

Graafian cells produces lots of oestrogen so oestrogen remains consistently high → positive feedback on ant pituitary → pituitary is very sensitive → LH surge

How is ovulation initiated?

 LH surge → removes mature egg from graafian cells → mature egg released into fallopian tube

What happens during the luteal phase?

 Corpus haemorrhagicum → corpus luteum → produces progesterone due to LH + Inhibin A → negative feedback to ant pituitary → stop LH

What are the phases of the ovarian cycle?

Follicular/pre-ovulatory phase (Day 1 – 14)

Ovulation (day 14)

Luteal phase (day 14-28)

What are the phases of the uterine cycle?

Menstrual phase (day 1-5)

Proliferative phase (Day 6-14 )

Secretory  phase (Day 14-28)

What happens during the menstrual phase?

Stratum functionalis shed (Stratum Basalis remains)

What happens during the proliferative phase?

o   Rebuild stratum functionalis

o   Rebuild spiral arteries

o   Rebuild uterine glands

o   Cervical glands produce thin mucous

o   DUE TO OESTROGEN

What happens during the secretory  phase?

o   Uterine gland secrete nutrient rich fluid

o   Cervical glands produce thick mucous

o   Thick layer of stratum functionalis

o   Longer spiral arteries

What happens if during the ovulation phase you fall pregnant?

Embryo produces HcG (acts as LH) → maintains corpus luteum → maintains progesterone for first 12 wks

What happens if during the ovulation phase you DON’T fall pregnant?

o   Corpus luteum degenerates→ corpus albicans → Progesterone stops

o   Spasms in spiral arteries, becomes weak and rupture → ischaemia in stratum functionalis → becomes necrotic → sheds as period

Cervical plug removed

How does the body decide if it is ready to be pregnant?

Adipocytes→ leptin→ signals brain fat stores enough for reproductive function → menarche

How is GnRH released and why is it important?

o   pulsatile GnRH release important: Continuous release leads to insensitivity of receptors

Define:

• Amenorrhea

• Oligomenorrhoea

• Menorrhagia

• Dysmenorrhea

Amenorrhea – Absence or cessation of menstruation

Oligomenorrhoea – ‘Few or scanty’ irregular and inconsistent menstrual bleeding – if menstrual cycle length >35 days

Menorrhagia – Heavy menstrual bleeding

Dysmenorrhea – Painful menstrual bleeding
Key terminologies

Primary vs secondary Amenorrhea

Primary amenorrhoea: Failure to menstruate by 15 with normal secondary sexual characteristics OR by 13 years of age with no secondary sexual characteristics

Secondary amenorrhoea: Cessation of menstruation for 3 – 6 months

What is Kallmann syndrome and what are the symptoms?

Failed migration of GnRH neurons from the nasal placode into the brain.
Characterised by GnRH deficiency + anosmia
Symptoms
• Primary amenorrhea
• Anosmia (loss of smell)
• Midline facial defects
• Renal agenesis

What is Sheehan syndrome and how can it cause amenorrhea?

complication of severe postpartum haemorrhage that damages the pituitary gland

does not release LH + FSH…

Ovarian causes of amenorrhea

Characterised by high FSH/LH
• Surgical removal (Oophorectomy )
• Radiation
• Pharmacological (Contraceptive pills)
• Idiopathic (Premature ovarian failure)

What are the different outflow obstructions that can cause amenorrhea?

Imperforate hymen
Transverse vaginal septum
Atresia of cervix (closed/absent)

** primary amenorrhea

What are the main categories of causes for amenorrhea?

Hypothalamic/ pituitary

ovarian

outflow obstruction

What are some suspected diagnoses with Oligomenorrhoea and how can you rule each out?

Hypothalmic Hypogonadotrophism if:

• ↓ FSH and LH / ↓ E2

• Often caused by stress, diet, excess exercise

Polycystic Ovarian Syndrome (PCOS) if:

• Normal FSH, normal/↑ LH, ↑ Testosterone

thyroid dysfunction if:

• Abnormal TFTs ( can be hypo or hyper)
  

What is the criteria to be diagnosed with Polycystic Ovarian Syndrome (PCOS)?

two of the following three criteria:

• Oligo-anovulation (infrequent or absent ovulation)

• Clinical and/or biochemical signs of androgen excess

• Polycystic ovarian morphology (PCOM)

What are some complications with PCOS?

• Infertility

• Cardiovascular disease

• Metabolic disorders:
  • Impaired glucose tolerance
  • Type 2 diabetes

• Endometrial cancer (due to no period (anovulation) but still having high oestogen)

How is Menorrhagia diagnosed?

Objective: > 80 ml of blood loss each period + / last longer than 7 days
Subjective: Reports of period becoming heavier, changing sanitary products every 1-2 hrs, or passing clots

What causes menorrhagia?

PALM COEIN

Polyp

Adenomyosis

Leiomyoma

Malignancy

Coagulopathy

Ovulatory dysfunction

Endometrial

Iatrogenic (Anticoagulants, Antiplatelets, copper IUD)

Not-yet-classified

What are Uterine fibroids?

Benign tumours of the myometrium.
Caused by proliferation of a mixture of smooth muscle cells and fibroblasts

Symptoms of Uterine fibroids

• menorrhagia +/ dysmenorrhoea

• Pain, pressure, or discomfort

• Urinary symptoms: frequency, urgency, urinary incontinence, or retention

• Bowel symptoms: bloating, constipation, and/or painful defecation

• Subfertility or infertility

Primary vs secondary Dysmenorrhoea

Primary dysmenorrhoea - pelvic pain during menstruation in the absence of pelvic pathology.
Secondary dysmenorrhoea - caused by an underlying pelvic pathology

causes of dysmenorrhoea

• Endometriosis

• Adenomyosis

• Uterine fibroids

• Pelvic inflammatory disease

• Intrauterine device

what is endometriosis?

Growth of endometrium-like tissue outside the uterus eg. on the ovaries, peritoneum, Uterosacral ligaments, Pouch of Douglas, Extra-pelvic

Hormonal changes → bleeding, chronic inflammation, and scar tissue formation

Symptoms of endometriosis

• Secondary congestive  dysmenorrhoea

• Deep dyspareunia

• Cyclical pelvic pain (peritoneal irritation)

• Cyclical painful defecation / bleeding per rectum during menses

•  Irregular bleeding

•  Infertility

Difference between endometriosis and adenomyosis

How do we treat Kallmann syndrome?

Pulsatile administration of GnRH with a programmed infusion pump—can have normal folliculogenesis, ovulation, and pregnancy