Gynae presentations - 1) Amenorrhoea Flashcards
What is primary and secondary amenorrhoea?
-
Primary: absence of menarche
- (girls aged 16+ with secondary sexual characteristics;
- aged 14+ without)
- Secondary: cessation of periods for ≥6 months after menarche (excluding pregnancy)
What are the main causes of amenorrhoea?
- hypothalamic
- pituitary
- ovarian
- adrenal
- genital tract abnormalities
What are the hypothalamic causes of amenorrhoea?
- Eating disorders (suppress GnRH),
- Hypo/hyperthyroidism,
- Kallmann syndrome
What are the pituitary causes of amenorrhoea?
- Prolactinomas (negative feedback on GnRH),
- Other pituitary tumours (mass effect),
- Sheehan’s syndrome,
- Post-contraception amenorrhoea (Depot causes downregulation of pituitary hormones)
What are the ovarian causes of amenorrhoea?
- Turner’s syndrome,
- Gonadal dysgenesis
- PCOS,
- Premature ovarian insufficiency/menopause
What are the adrenal causes of amenorrhoea?
- Mild CAH
What are the genital tract abnormalities causes of amenorrhoea?
-
Congenital obstruction to normal menses flow e.g.,
- vaginal septum,
- imperforate hymen,
- Rokintansky syndrome,
-
Iatrogenic obstruction to menses flow e.g.,
- cervical stenosis
- Asherman’s syndrome
What is oligomenorrhoea?
Oligomenorrhoea:
- irregular periods
- with cycle length >35d
- and/or <9 periods/year
What must be looked for on examination in a woman presenting with amenorrhoea?
-
BMI
- (high ~ = PCOS, low ~ = eating disorder)
-
Assess for features of:
- Cushing’s syndrome (striae, buffalo hump, significant central obesity, easy bruising, hypertension, and proximal muscle weakness)
- Hypo-/hyperthyroidism
-
Excess androgens (hirsutism, acne) + features of virilization (hirsutism, acne, deep voice, temporal balding, increase in muscle bulk, breast atrophy, and clitoromegaly)
- (~ = PCOS, CAH, androgen-producing tumour of the ovaries, adrenals, pituitary, etc.)
-
Decreased endogenous oestrogen (reddened or thin vaginal mucosa)
- (~ = premature ovarian insufficiency, etc.)
-
Hyperprolactinaemia (galactorrhoea)
- (~ = prolactinoma, hypothyroidism, etc.)
-
Visual field assessment
- (~ = pituitary tumour)
-
Bimanual examination
- (~ = genital tract abnormalities e.g., vaginal septum, imperforate hymen, etc.)
What are the Ix in a woman presenting with amenorrhoea?
- Pregnancy test
-
Bloods:
- TFTs,
- Prolactin,
- LH, FSH,
- Testosterone, oestrogen, 17-hydroxyprogesterone
- Progesterone challenge to elicit a withdrawal bleed (no bleed suggests low oestrogen/outflow obstruction)
- Karyotyping
- USS (malformations, Turner’s, PCOS)
- Hysteroscopy
Suggest what might be seen on FSH and LH in different causes of amenorrhoea
- High FSH and LH levels on two occasions suggest premature ovarian insufficiency (in women younger than 40 years of age)
- Normal or low FSH levels and normal or low LH levels suggest hypothalamic causes (weight loss, excessive exercise, stress, or rarely, a hypothalamic or pituitary tumour)
- Normal FSH levels and normal or moderately increased LH levels may be found in PCOS
Suggest what might be seen on testosterone in different causes of amenorrhoea
- High levels of total testosterone (5.0 nanomol/L or greater) warrant investigation to exclude other causes, such as Cushing’s syndrome, late-onset congenital adrenal hyperplasia, or an androgen-secreting tumour
- A moderately increased testosterone level (2.5–5.0 nanomol/L) may be seen in PCOS.
What must be seen on transvaginal/transabdominal USS to diagnose PCOS?
Polycystic ovaries on US =
- presence of ≥12 follicles (measuring 2–9 mm in diameter) in one or both ovaries
- and/or increased ovarian volume (greater than 10 cm3)
What is the cause of PCOS?
The 2 main hormonal abnormalities are:
-
Insulin resistance
- Leads to high insulin levels
- Insulin promotes androgen production (possibly directly or through LH) and suppresses hepatic SHBG production (leading to higher levels of free circulating androgens)
-
Excess LH
- Due to increased GnRH pulse frequency (which may be due to excess insulin)
- Stimulates ovarian androgen production
- LH is increased relative to FSH
- Despite high LH levels, the LH surge is suppressed (due to increased androgens) → anvovulation
- Follicles develop within the ovary but are arrested at an early stage remain visible as cysts
What are the RFs for PCOS?
- FHx,
- premature adrenarche,
- obesity (exacerbates severity),
- DM
What are the signs & symptoms of PCOS?
- Oligomenorrhoea or amenorrhoea (75%)
- 40% have anovulatory cycles
- Subfertility (75%)
- Obesity (40%)
- Hirsutism
- Acne
- Acanthosis nigricans
- HTN
What are the criteria for diagnosing PCOS?
- Rotterdam criteria for diagnosis (2 of the following):
- Oligo- or anovulation
- Clinical and/or biochemical signs of hyperandrogenism
- Polycystic ovaries on imaging
What are the Ix for PCOS?
- Bloods:
- To aid diagnosis:
-
Serum total and free testosterone, and serum dehydroepiandrosterone sulfate (DHEAS)
- Raised
-
LH & FSH
- Raised LH, raised LH:FSH ratio → >3:1
- Now not essential for diagnosis
- Day 21 progesterone (low – suggests anovulation)
- SHBG (low)
-
Serum total and free testosterone, and serum dehydroepiandrosterone sulfate (DHEAS)
- To exclude other causes (PCOS is largely a diagnosis of exclusion)
- TFTs, prolactin, 17-hydroxyprogesterone
- To aid diagnosis:
- OGTT and fasting lipid panel
-
TVUSS
- ≥12 follicles in each ovary, 2-9mm in diameter, and/or increased ovarian volume (>10ml)
What is the Mx of PCOS?
Tailored to the symptoms and need for fertility
Lifestyle advice (for all patients)
- Weight management → having normal BMI can reduce symptoms/trigger menstruation
- Promote healthy diet and exercise
- Hair removal (e.g. laser hair removal, hair removal cream)
- Also treat underlying conditions (DM, HTN)
Treatment of oligo/amenorrhoea:
- Need to induce bleeds because unopposed oestrogen (without progesterone) can cause endometrial hyperplasia
-
COCP (2nd line after weight loss)
- Also increases SHBG → helps to reduce androgenic symptoms
-
Metformin (3rd line)
- Insulin sensitiser; improves menstrual irregularity and restores ovulation; improves insulin sensitivity
- Also improves hyperandrogenic symptoms by decreasing testosterone and increasing SHBG
-
Cyclic oral progestogen (4th line)
- If COCP is contra-indicated, or in refractory cases
Treatment of hyperandrogenic features (hirsutism, acne):
- COCP (1st line)
- Metformin (adjunct)
-
Anti-androgen (e.g. spironolactone, finasteride)
- Avoid in pregnancy (cause ambiguous genitalia)
Treatment of infertility (if desiring fertility):
-
Metformin
- Weight loss should be tried first; metformin added if no response
- Lower live birth rate than clomifene but no increased risk of multiple pregnancy
-
Clomifene (1st esp in normal weight women)
- Anti-oestrogen → blocks oestrogen receptors in hypothalamus/pituitary → increased FSH and LH
- Given on days 2-6; stepwise dose increase induces follicular maturation and ovulation
- 10% risk of multiple pregnancy, risk of ovarian hyperstimulation syndrome
- Metformin can be added if not responsive
-
Gonadotrophins (2nd line)
- Used if clomifene has failed
- Daily SC injections
- Risk of multiple pregnancies and ovarian hyperstimulation syndrome
-
IVF or laparoscopic ovarian drilling (3rd line)
- Laparoscopic ovarian drilling uses laser to reduce the amount of functional ovarian tissue to reduce androgen and inhibin production restores FSH levels and ovulation
What are the complications and prognosis of PCOS?
Complications:
- T2DM later in life (50%) and GDM (30%)
- Increased risk of endometrial cancer (due to unopposed oestrogen)
There is no cure for PCOS so treatment should be continued through reproductive years
- Improves after menopause
What is Ashmerman’s sydrome?
Rare condition in which scar tissue or adhesions partially or completely occlude the uterine cavity
Aetiology of Ashmerman’s sydrome?
Due to damage of the basal layer of endometrium
- Basal layer does not regenerate → fibrosis and adhesion formation inside uterine cavity
- Occurs after trauma (from instrumentation, e.g. D&C, ERPC, myomectomy), or infection (endometritis)
What are the signs and symptoms of Asherman’s syndrome?
- Amenorrhoea or reduced menstrual bleeding
- Dysmenorrhoea or cyclical abdominal pain
- Subfertility
What are the Ix for ?Asherman’s syndrome?
- Ix for subfertility
- Hysteroscopy (gold standard)
- Other:
- Hysterosalpingogram (HSG): dye injected into cervix; X-rays visualise uterine cavity defects
- Saline hysterosonography (TVUSS with saline in uterus)
What is the Mx of Asherman’s syndrome?
Treatment is not needed if not planning to conceive & asymptomatic
Hysteroscopic adhesionolysis
- To manually break down adhesions
- Risks further trauma → scarring may recur
- Reduce risk of adhesion recurrence with copper IUD and PO oestrogens (induce endometrial proliferation)
- Reassess cavity 2-3 months later
Fertility treatment may be needed
What are the complications and prognosis of Asherman’s syndrome?
Complications:
- Subfertility
- If patient does conceive, increased risk of miscarriage, placenta praevia and placenta increta
Menstrual disturbance often improves after treatment; post-treatment pregnancy rates are 50%
What is menopause?
Permanent cessation of menstruation, defined as 12 months after the final period
What is difference between:
- perimenopause
- early menopause
- premature ovarian insufficiency?
Perimenopause: time from the beginning of the first features of menopause, until 12 months after the last period
Early menopause: menopause in a woman aged 40-45yo
Premature ovarian insufficiency: menopause in a woman <40yo
What is the aetiology of menopause? Which other symptoms may be seen and why?
Hormonal changes:
- Decreased follicular activity (due to reduced quality and quantity of eggs) causes reduced oestrogen secretion from ovaries
- LH and FSH rise due to low oestrogen and inhibin (so removal of negative feedback)
- Irregular bleeding occurs → some bleeds are menstruation from ovulatory cycles; others are anovulatory cycles which can occur up to every fortnight
Symptoms are due to hormonal changes
- Vasomotor symptoms: due to pulsatile LH influencing temperature control
- Urogenital symptoms: uterus, vagina, bladder and urethra are maintained by circulating oestrogen → decreased oestrogen causes atrophy of vagina/bladder/urethra and thinning of myometrium
- Bone density: oestrogen reduces osteoclast activity → drop causes increase bone resorption
- Ischaemic heart disease: oestrogen is protective by reducing LDL and raising HDL
Aetiology of premature ovarian insufficiency?
- In most women no cause is found, but causes can include:
- Primary POI: chromosomal abnormalities (Turner’s), autoimmune diseases (hypothyroid, Addison’s, myasthenia gravis), enzyme deficiencies (CAH)
- Secondary POI: surgical following bilateral oophorectomy, chemo/radiotherapy, infections
- It can be reversible, so is not termed an early menopause
- May experience unpredictable spontaneous ovarian activity → irregular vaginal bleeding and small risk/chance of pregnancy
What are the signs and symptoms of menopause/early menopause/POI?
-
Persistent amenorrhoea
- Often initial oligomenorrhoea or irregular/shortened cycles
- Vasomotor symptoms: hot flushes, night sweats, palpitations, headaches
- Urogenital symptoms: vaginal dryness, dyspareunia, frequency, dysuria, recurrent UTIs
-
Psychological symptoms: poor concentration, lethargy, mood disturbance, reduced libido
- Usually the first to present
What are the Ix for menopause/early menopause/POI?
- Largely clinical diagnosis
- Pregnancy test (for everyone)
-
Bloods:
- In women <45yo; not recommended in >45yo
-
FSH: >30Iu/L is high → indicated menopause
- Increased levels suggest fewer oocytes remaining in the ovaries
- Varies throughout the cycle → best measured between days 2-5
- Oestradiol: low
-
Anti-Mullerian hormone (AMH): low
- Direct measurement of ovarian reserve; stable throughout menstrual cycle
- Exclude other causes of symptoms: TFTs, catecholamines and 5-hydroxyindolacetic acid (phaeo and carcinoid syndrome), progesterone (low indicates anovulation), prolactin
-
TVUSS
- Only if uncertainty
-
DEXA scan
- If RFs for osteoporosis (early menopause, low BMI, FHx, corticosteroids etc.)
What is the Mx for menopause/early menopause/POI?
Conservative measures:
- Stop smoking, regular exercise, healthy eating, avoid alcohol and caffeine
- To improve symptoms and address long-term health
- Some women try alternative therapies (acupuncture, evening primrose oil)
- May be sufficient for some women
Hormone replacement therapy (HRT):
- For women who cannot tolerate the symptoms; and in POI until 50yo
- Regimens:
-
Women with a uterus: oestrogen + progestogen
- Unopposed oestrogen increases risk of endometrial hyperplasia and carcinoma (progesterone is given to counteract this)
- Usually given as norethisterone/oestradiol transdermal patch; changed twice weekly
- May be given orally; oestrogens are sometimes given as implant; progestogens are sometimes given as IUS
- Perimenopausal women are given cyclic therapy (continue to bleed); postmenopausal women are given continuous therapy
- Women without a uterus (or IUS fitted in last 5yrs): oestrogen (as above)
-
For urogenital atrophy (without other symptoms): topical oestrogen
- Progesterone is not needed (don’t increase systemic oestrogen)
- Cream, ring, pessary
-
For reduced libido: methyltestosterone
- Patch or subcutaneous implant
- Not successful in all women → other factors may be involved
- NB tibolone is sometimes used as an alternative → oestrogenic, progestogenic and androgenic actions
-
Women with a uterus: oestrogen + progestogen
POI:
- HRT until 50yo
- Oocyte donation for fertility treatment
- Supportive care and counselling
What are the risks and benefits of HRT?
Benefits of HRT:
- Menopausal symptoms: reduces hot flushes and urogenital symptoms
- Libido may be improved by oestrogen alone or may need testosterone in addition
- Reduces risk of osteoporosis
- Reduces risk of colorectal cancer and may slightly reduce risk of CVD
Risks of HRT:
- Breast cancer: combined HRT (but not oestrogen alone) increases risk
- Effect is not seen in women who start oestrogen early for premature ovarian insufficiency (not seen below 50yrs) suggests lifetime exposure is relevant
- Endometrial cancer: unopposed oestrogen increases risk
- Venous thromboembolism: oral HRT increases risk 2x
- Gallbladder disease: risk increased by oral HRT
What is the duration of therapy for different types of ‘menopause’?
- Menopausal symptoms: 5yrs then stop to assess whether still needed
- Premature menopause/POI until 50yo: continue until 50yo
- Osteoporosis: treatment may need to be lifelong
What are some other Mx options for types of ‘menopause’?
Other management options (considered if HRT contraindicated or insufficient):
- SSRIs may be effective for hot flushes
- Lubricants and moisturisers for vaginal atrophy
- Osteoporosis treatments, e.g. vitamin D/calcium, bisphosphonates
What are the complications and prognosis of menopause?
Complications:
- CVD → same risk as men after menopause
- Osteoporosis
- Depression increases during perimenopausal period
Troublesome symptoms usually decrease after 5 years; may persist (esp vaginal dryness
