O&G JC106: Climacteric Symptoms: Menopause And Related Illness, Amenorrhoea Flashcards
Hypothalamic-Pituitary-Ovarian axis (HPO axis)
Hypothalamus –> GnRH
–> Pituitary –> FSH, LH
–> Ovary –> Estrogen (-ve feedback)
–>
1. Growth of dominant follicle in the beginning of Follicular phase
2. Thickening of endometrial lining
LH surge
–> Ovulation
–> ↑ Progesterone level
Amenorrhoea
Definition:
- Absence of menstrual period in a woman of reproductive age
- A symptom, NOT diagnosis (∵ many causes)
- Primary vs Secondary
Primary amenorrhoea:
- Absence of menstruation by age **16 (if presence of normal secondary sexual characteristics)
(Investigate by age **14 if no secondary sexual characteristics: indicate low Estrogen level)
—> Congenital / Genetic abnormalities
—> Disturbance of normal endocrinological events of puberty
—> ALL causes of Secondary amenorrhoea can also present as primary amenorrhoea if occur early enough
Secondary amenorrhoea:
- Absence of menstruation for ***6 months in a woman who has menstruated before
(Oligomenorrhoea:
- Have period but Cycle length >35 days
- Investigations / Management similar to Secondary amenorrhoea ∵ lots of overlap)
Causes of Amenorrhoea
- Physiological
- Pre-pubertal
- Pregnancy + Lactation
- Post-menopausal
- Contraceptives - Pathological (in HPO axis)
Endocrine:
- Hypothalamus / CNS disorders
- Pituitary disorders
- Ovary disorders
- Thyroid disorders (Hyper / Hypo)
- Adrenal disorders (Tumour, Cushing’s, CAH)
Anatomical:
- Outflow tract obstruction
- Uterus disorders (e.g. absence of uterus)
- Endometrial damage (e.g. Asherman’s syndrome)
Hypothalamus / CNS disorders
Not enough GnRH secreted
1. Functional hypothalamic amenorrhoea (CNS effect)
- weight loss
- over exercise
- stress
- eating disorders (e.g. anorexia nervosa)
- systemic illness
- ***Kallmann syndrome
- congenital hypogonadotrophic hypogonadism (isolated GnRH deficiency) associated with anosmia - Idiopathic hypogonadotrophic hypogonadism
- Tumours e.g. ***Craniopharyngioma
- Cranial irradiation
Pituitary disorders
Hyperprolactinaemia:
1. ***Prolactinoma
2. Non-functioning adenoma (stalk effect)
3. Other causes of Hyperprolactinaemia (prolactinoma may be a cause)
Hypopituitarism:
1. ***Sheehan’s syndrome
- follow severe post-partum haemorrhage (∵ severe hypotension –> severe hypovolaemia –> ischaemia + necrosis of pituitary –> hypopituitarism following delivery)
2. Iatrogenic: Surgery / RT
Other endocrinopathies:
1. Thyroid dysfunction (Hyper / Hypo)
***Causes of Hyperprolactinaemia (SpC O&G)
- ***Pregnancy, Lactation
- Stress (transient)
- ***Prolactinoma
- Other pituitary tumours, non-functioning “disconnection” tumour —> disrupt inhibitory influence of Dopamine on Prolactin
- ***Primary hypothyroidism
- Drug inhibiting Dopamine secretion
- **Dopaminergic antagonist
- Phenothiazine (+ Other Typical antipsychotics)
- **Domperidone
- ***Metoclopramide
- Cimetidine
- Methyldopa
Ovary disorders
- Primary ovarian insufficiency (POI) (loss of function of ovaries ~ menopause; In contrast to PCOS (ovaries are actually working))
- **Gonadal agenesis / dysgenesis
—> ∵ chromosomal / non-chromosomal problems (e.g. **Turner syndrome / variant, **Fragile X premutation (but not full blown Fragile X))
- **Iatrogenic
—> Surgery: Bilateral oophorectomy for ovarian tumours
—> RT to pelvis
—> Chemotherapy
- ***Autoimmune
- Idiopathic - Polycystic ovary syndrome (PCOS)
- Androgen-secreting ovarian tumour (rare)
Polycystic ovary syndrome (PCOS) (多囊卵巢綜合症)
- Disorders of ovary (but ovaries are working vs Ovarian insufficiency)
- Endocrine disturbance –> Oligo / Anovulation
Diagnosis (**Rotterdam criteria, 2 out of 3):
1. Oligo-anovulation
2. Clinical / Biochemical hyperandrogenism (e.g. hirsutism, ↑ acnes)
3. Sonographic features of polycystic ovaries (Follicle number per ovary **>=20, each 2-9mm / Ovarian volume ***>=10ml, String of pearls sign) (ONE ovary is sufficient for definition)
Exclusion of other etiologies with similar clinical features:
- Thyroid disorders
- Hyperprolactinaemia
- POI
- Hypogonadotrophic hypogonadism
- **Non-classic CAH
- **Cushing’s syndrome
- ***Adrenal tumours (androgen-secreting (self notes))
- etc.
Long-term health sequalae of PCOS:
1. **Metabolic syndrome (HT, DM, HL, CVS disease)
2. **Infertility (∵ anovulation)
3. ***Endometrial hyperplasia / cancer (∵ unopposed estrogen)
Outflow tract / Uterus disorders
End organs in which hypothalamic, pituitary, ovarian hormones act on
1. Outflow tract obstruction (at different levels, generally congenital –> primary amenorrhoea usually)
- **Cervical / Vaginal atresia
- **Transverse vaginal septum
- **Imperforate hymen
S/S:
- **Cyclical abdominal pain (∵ trapped period –> distension)
- **Pelvic mass
- **Endometriosis (∵ backflow of period)
- Vagina / Uterus absence
- Endometrial destruction leading to obstruction
- **TB endometritis
- **Asherman’s syndrome (intrauterine adhesions following surgery e.g. suction, evacuation, myomectomy) –> causes problems e.g. infertility, amenorrhoea, recurrent miscarriage
(Congenital abnormality in Mullerian development (i.e. uterus):
- Isolated defect (absence / hypoplasia of uterus)
- Androgen insensitivity syndrome
- 5α-reductase deficiency
Congenital defect of Urogenital sinus development (i.e. outflow tract):
- Agenesis of lower vagina
- Imperforate hymen
Damage to endometrium:
- Asherman syndrome
- TB endometritis)
Androgen insensitivity syndrome (AIS)
Androgen receptor mutation
- ***46XY (in a girl) (I.e. born a male, but phenotype girl)
- Androgen receptors resistant to androgens
- Testosterone: High-Normal / Slightly elevated male range
- Estradiol: Upper normal male range
S/S:
1. Primary amenorrhoea
2. Female external genitalia (∵ Non-virilisation of genitalia –> Female phenotype)
3. Undescended gonads
4. No axillary / pubic hair
5. Some breast development (∵ peripheral conversion of androgen –> estrogen)
6. Inguinal masses / hernia
7. Absent uterus (AMH: Anti-mullerian hormone)
8. Short vagina
Associated health problems:
1. Testicular malignancy
2. Hypoestrogenism (after gonadectomy)
Treatment:
1. HRT (after gonadectomy (remove testes))
2. Fertility: Child adoption
3. Sexuality: Vaginal dilation / reconstruction (let the male live as a female instead)
Summary of causes of Amenorrhoea
Primary amenorrhoea:
- MUST rule out:
1. Absence of uterus / outflow tract obstruction / disorders of sex development (AIS, Swyer syndrome)
2. All causes of secondary amenorrhoea (∵ can cause primary amenorrhoea if occurs before they have first ever period)
Secondary amenorrhoea:
- Women MUST have had:
1. Patent lower genital tract
2. Endometrium that is responsive to ovarian hormone stimulation
3. Ovaries that have responded to pituitary gonadotrophins
–> ∴ can rule out congenital causes
***History taking of Amenorrhoea
- Onset + Duration
- Previous menstruation (determine primary / secondary amenorrhoea)
- ***Pubertal development
- growth spurt and age it occurred
- development of pubic / axillary hair / breast - ***Nutrition, Stress, Weight change, Excessive exercise
- indicate hypothalamic cause - ***Galactorrhoea, headache, visual disturbance
- indicate hyperprolactinaemia / prolactinoma - ***Menopausal symptoms
- e.g. hot flushes / dryness –> indicate POI - ***Thyroid symptoms
- hyper / hypothyroidism - ***Hyperandrogenic symptoms (e.g. Adrenal tumour, Androgen-secreting ovarian tumour, Cushing’s, PCOS)
- e.g. ↑ acne, hirsutism, male pattern baldness - Congenital symptoms
- ***Anosmia (Kallmann syndrome) - ***Anatomical symptoms
- Cyclical abdominal pain
- Urinary retention - Past medical, surgical
- previous OG history, cervical smear, fertility wish
- previous chemo, RT, surgery (POI)
- previous **ovarian surgery, dilatation, curettage (Asherman’s syndrome)
- previous *PPH (Sheehan’s syndrome) - Sexual history
- ***pregnancy - Drug history
- long-term medications
- ***contraceptives - Social history
- Family history
Rmb: ALWAYS rule out ***pregnancy! (∵ commonest cause of amenorrhoea in reproductive age women!)
***Physical examination of Amenorrhoea
- Body height, weight, BMI (compare with previous BMI)
- ***Stigmata of chromosomal abnormality (Turner syndrome)
- ***Galactorrhoea, visual field
- ***Goitre, Thyroid signs
- **Cushingoid features / **Hirsutism / Virilisation (Ferriman-Gallwey hirsutism scoring system: 9 body areas most sensitive to androgen (score 0-4))
- ***Secondary sexual characteristics
- Abdominal mass
- Genital tract development / PR exam
- clitoromegaly (sign of hyperandrogenism)
- pubic hair distribution + maturity (Tanner stage for pubic hair)
- swelling of introitus (outflow tract obstruction)
- hymen
- vaginal length
- presence of cervix / uterus / ovaries
- may be difficult to assess in patients not been sexually active –> inspect introitus, genitalia, imaging
Rmb: ALWAYS rule out ***pregnancy! (∵ commonest cause of amenorrhoea in reproductive age women!)
***Investigations of Amenorrhoea
1st line:
1. ***Pregnancy test (exclude pregnancy!!!)
-
**Hormonal profile
- **FSH, LH —> check HPO axis
- **Estradiol —> check HPO axis
- **Prolactin —> exclude hyperprolactinaemia
- ***Testosterone —> (<5: PCOS, >5 more likely androgen-secreting tumour)
- TFT —> exclude thyroid disorders -
**Progestogen challenge test (Provera withdrawal test) (通經藥)
- give progestogen for 1 week
–> withdrawal bleeding (+ve test) –> sufficient Estrogen in body resulting in sufficient endometrial thickness –> when progestogen withdrawn –> shedding of endometrium –> amenorrhoea is due to **Anovulation
–> no withdrawal bleeding (-ve test) –> insufficient Estrogen in body (∴ thin lining) or Anatomical problems - ***USG pelvis
- Uterus / Ovarian morphology (e.g. PCOS) / presence / absence
Other investigations (depending on cause)
5. Hormonal
- **Androgens (SHBG, 17-OH progesterone –> CAH) (if significant virilisation / hirsutism)
- **E+P withdrawal test (when -ve progestogen challenge test –> if now +ve (有翻bleeding) –> indicate low endogenous Estrogen level rather than Anatomical problems)
- Dynamic tests: e.g. GnRH test for pituitary function
- Genetic
- ***Karyotype (Primary amenorrhoea, POI) (e.g. Turner syndrome)
(if suspect primary amenorrhoea / disorders of sex differentiation ∵ ambiguous genitalia, absent uterus)
- Fragile X premutation (POI) - Radiological
- 3D USG pelvis / MRI / USG renal tract (∵ common embryonal origin as pelvic organ –> examine whether there is co-existing congenital urinary tract problem) –> examine congenital uterine abnormality
- **Pituitary imaging
- **CT adrenal glands - Visual field by perimetry
- Laparoscopy / Hysteroscopy
- if suspect congenital uterine problem - Autoimmune screening (for POI)
- Anti-thyroid Ab (Anti-TPO)
- Anti-adrenal Ab
***Diagnostic approach to Amenorrhoea
Presented with amenorrhoea
–> History + P/E + **Pregnancy test
–> Negative
–> **Hormonal profile (FSH, Estrogen, Prolactin, TFT, **Provera (Progestogen) withdrawal test)
–>
1. FSH ↑ –> **POI –> Karyotype / Fragile X / Autoimmune functions
- FSH ↓ –> ***hypogonadotrophic hypogonadism –> MRI to exclude hypothalamic / pituitary tumour
- FSH normal
–> Withdrawal +ve –> Pelvic USG to rule out **PCOS
–> Withdrawal -ve –> **Endometrial / Outflow tract problems - Prolactin ↑ –> MRI to exclude ***pituitary tumour
- TFT abnormal –> Refer physician
