JC 106 (O&G) - Climacteric symptoms Flashcards
Define primary and secondary amenorrhea
Primary - Absence of menstruation by age 16
Secondary - Absence of menstruation for 6 months in a woman with previous menstruation
6 major groups of causes of amenorrhea
Physiological
Disorders of hypothalamus/ CNS
Disorders of pituitary
Disorders of ovary
Disorders of outflow tract and/ or uterus
Androgen insensitivity syndrome (AIS)
List physiological causes of amenorrhea
Pre-pubertal
Pregnancy & lactation
Postmenopausal
List CNS/ hypothalamic causes of Amenorrhea
CNS effect, e.g. weight loss, over-exercise, stress, eating disorders (e.g. anorexia nervosa)
Kallmann’s syndrome (X-linked/autosomal recessive hypogonadotrphic hypogonadism)
Idiopathic hypogonadotrophic hypogonadism
Tumours, e.g. craniopharyngioma causing growth hormone deficiency
List pituitary causes of amenorrhea
Sheehan’s syndrome (severe postpartum hemorrhage causing hypopituitarism)
Prolactinomas (suppress GnRH secretion, inhibit gonadotrophins (FSH, LH)
Non-functioning adenoma
Iatrogenic: surgery, radiotherapy
Other endocrinopathies:
Hyperprolactinaemia (e.g. prolactinoma)
Thyroid dysfunction (TRH also regulates the synthesis and release of prolactin)
Congenital adrenal hyperplasia
List ovary causes of amenorrhea
Premature ovarian insufficiency
Gonadal agenesis/ dysgenesis: chromosomal/ non-chromosomal
Iatrogenic: surgery (bilateral oophorectomy), radiotherapy to pelvis, chemotherapy
Autoimmune
Polycystic ovary syndrome (ovaries are working but hormonal disturbance)
Clinical diagnostic criteria for PCOS
Rotterdam consensus: 2 out of the 3 criteria
1) Oligo-anovulation
2) Clinical/ biochemical hyperandrogenism
3) Sonographic features of polycystic ovaries:
Follicle number per ovary of >20; and/or
An ovarian volume >=10ml
List outflow tract/ uterus causes of amenorrhea
Outflow tract obstruction
Cervical/ vaginal atresia
Transverse vaginal septum
Imperforate hymen
Absence of vagina/ uterus
Endometrial destruction:
TB endometritis
Asherman’s syndrome (severe intrauterine adhesions, usually following surgery, e.g. suction, evacuation)
Features of Androgen insensitivity syndrome (AIS)
Androgen receptor mutation in 46XY:
Non-virilisation of genitalia - female phenotype
Undescended gonads
No axillary/pubic hair
Some breast development (peripheral conversion of androgen into oestrogen)
Clinical presentation of outflow tract/ uterine obstruction
- primary amenorrhea with cyclical abdominal pain (due to distension)
- pelvic mass, endometriosis (due to backflow of period)
Approach to primary amenorrhea
- Indication for investigation
- Which conditions to rule out
Investigate by age 14 if no secondary sexual characteristics (low estrogen levels)
Must rule out: Outflow tract obstruction Absence of uterus Disorder of sex development: AIS Swyer syndrome (46,XY but mutant SRY) All causes of secondary amenorrhoea occuring before first period
Outline history taking questions for amenorrhea
Onset, duration
Menstrual history:
Previous menstruation (1o or 2o)
Pubertal development (growth spurt, age, pubic/axillary hair, breast)
Ddx:
Menopausal symptoms (hot flushes, vaginal dryness, premature ovarian insufficiency)
Nutrition, stress, weight change (hypothalamic)
Galactorrhoea, headache, visual disturbance (pituitary)
Thyroid symptoms (hyper or hypo)
Hyperandrogenic symptom (acnes, hirsutism, male-pattern balding)
Family history of genetic diseases
Iatrogenic causes:
Past medical history (chemotherapy, radiotherapy, surgery)
Drug history (long-term medications)
Outline P/E for amenorrhea
General:
Body height/ weight, calculate BMI - PCOS risk
Stigmata of chromosomal abnormalities
Sexual characteristics:
Hirsutism/ virilisation
Secondary sexual characteristics
Genital tract development (observe introitus, external genitalia; imaging if needed)
Associated endocrine dysfunction:
Goitre
Galactorrhoea, visual field
Abdominal mass (pregnancy, PCOS, undescended testes)
First-line investigations for amenorrhea
Pregnancy test (always rule out pregnancy)
Hormonal profile: FSH, LH, E2, PRL, TFT, testosterone
Progestogen (Provera) challenge test (give a course of progestogen for a week then stop):
- Positive result (i.e. gets period after): estrogen production is normal in the body giving endometrial thickness
- Negative result (i.e. no period after progestogen): endometrial lining quite thin, hence low estrogen
USG pelvis
WHO classification of anovulation
Define the hormonal disturbance in each class
Class 1 hypogonadotrophic hypogonadism - Hypothalamic/ pituitary causes
- Low FSH, LH
- Low Estradiol
- or high prolactin
Class 2: normogonadotrophic anovulation - Uterine outflow obstruction
- Normal FSH, LH and Estradiol
Class 3: hypergonadotrophic hypogonadism - Ovarian dysfunction
- High FSH, LH
- LOW Estradiol
Class 1 anovulation
- Hormone disturbance
- Investigations for underlying cause
Class 1: hypogonadotrophic hypogonadism
- Low FSH, LH, Estradiol
- Or high prolactin
Investigations:
- Visual field perimetry
- MRI to exclude tumour in hypothalamus/ pituitary stalk lesion
- +/- dynamic test: GnRH stimulation test for pituitary function
- Thyroid function (hypothyroidism, High TSH induce Prolactin)
- Renal function test (Renal failure = decrease PRL clearance, increase dopamine excretion)
- Pelvic USG - PCOS
- Genetic test: PRLR mutation
Class 2 anovulation
- Hormone disturbance
- Investigations for underlying cause
Class 2: normogonadotrophic anovulation
Normal FSH, LH, Estradiol
Investigations:
- Provera withdrawal test positive - pelvic ultrasound to exclude PCOS
- Provera withdrawal test negative - endometrial/ outflow tract problems/ anatomical anomalies:
i) 3D USG/ MRI pelvis
ii) USG renal tract (common embryonic origin)
iii) laparoscopy/ hysteroscopy
Class 3 anovulation
- Hormone disturbance
- Investigations for underlying cause
Class 3: hypergonadotrophic hypogonadism
High FSH, LH but low estradiol
Suspect premature ovarian insufficiency (POI)
- Confirm diagnosis: FSH >25 IU/L twice over 4 weeks apart
Genetic tests:
i) Karyotype (primary amenorrhoea): Turner syndrome, disorders of sex differentiation (ambiguous genitalia, absent uterus)
ii) Fragile X premutation
Autoimmune screening: anti-thyroid Ab, anti- adrenal Ab vs ovaries
MRI pelvis: Structural lesions (Ovarian cancer, Iatrogenic damage…etc)
DXA scan (risk of osteoporosis)
Investigations for significant virilization/ hirsutism/ raised testosterone
Test for androgens:
SHBG/ sex hormone binding globulin
17-OH progesterone (if raised = congenital adrenal hyperplasia)
Test for low estrogen levels
Negative progestogen challenge/ Estrogen and progesterone withdrawal test
Withdrawal with no bleeding = low endogenous estrogen level
Treatment of amenorrhea: Hypogonadotrophic hypogonadism
- Hypothalamic functional causes: lifestyle (stress, eating disorder, excessive exercise), reassurance and observe, psychological treatment
- Neurosurgery for hypothalamic-pituitary lesions
- Estrogen therapy for primary amenorrhea and induce puberty
- Maintenance HRT (E+P) against osteoporosis
- Exogenous gonadotrophins for fertility issue (e.g. Follitropin, Lutropin a)
Treatment of PCOS
Weight reduction (restore ovulation + prevent metabolic disorder in long term)
Menstrual regulation to prevent endometrial hyperplasia/CA due to unopposed estrogen:
- Periodic progestogen for withdrawal bleeding
- Combined OC pills
Hirsutism:
- Combined OC pills
- cosmetic measures (laser, shaving)
- anti- oestrogens (spironolactone)
Fertility:
Letrozole (1st line)
Gonadotrophin
Laparoscopic ovarian drilling
Treatment for premature ovarian insufficiency
Primary amenorrhea: estrogen to induce puberty
Maintenance HRT (E+P) against osteoporosis until age 51
Fertility:
Oocyte donation
Adopt children
Treatment for hyperprolactinaemia
Dopaminergic drugs e.g. bromocriptine, cabergoline
Neurosurgery (rarely)
Treatment for outflow tract/ uterine obstruction causing amenorrhea
Surgical correction of congenital anomalies/ outflow tract obstruction (e.g. vaginal dilation for vaginal atresia)
Define climacteric and menopause
Climacteric:
- the years of waning ovarian function
- Marks the transition from the reproductive to the non-reproductive state
Menopause:
- a specific event (the final menstrual period)
- diagnosed retrospectively after cessation of menses for 12 months in previously cyclical women
- permanent cessation of ovarian function and fertility
Define the time period for perimenopause
Begins with the first clinical, biological and endocrinological features of the approaching menopause
Ends 12 months after the final menstrual period
Can last for several years
post-menopause = after perimenopause
Define 3 clinical types of menopause
Natural menopause
- Clinically diagnosed in retrospect following spontaneous amenorrhoea for 12 months
- without other obvious pathological/ physiological cause (mean age 51 years)
Artificial/ induced menopause
- Sudden termination of menstrual life due to surgery/ radiotherapy/ chemotherapy
Premature ovarian insufficiency
- Loss of ovarian function before age 40 yrs
Hormonal changes at menopause
Decline in number of ovarian follicles
- Decrease Estradiol
- Decrease inhibins and loss of negative feedback»_space; Increase FSH and LH»_space; stimulates ovarian stroma to produce androgens»_space; peripheral conversion to estrone
List 4 major categories of climacteric symptoms
Vasomotor symptoms
Psychological symptoms
Sexual dysfunction
Urogenital atrophy
List vasomotor symptoms due to menopause
Hot flushes
Sweating
Palpitation
Dizziness
List psychological symptoms due to menopause
Loss of energy and drive Loss of concentration Irritability Anxiety Depression Mood fluctuations Sleep disturbances
List sexual dysfunctions due to menopause
Dyspareunia (atrophic change)
Decreased libido (Can be multifactorial)
List urogenital atrophy symptoms due to menopause
Vagina: Dryness Burning Pruritus Dyspareunia Prolapse
Urinary: Urgency Frequency Dysuria Urinary tract infection Incontinence Voiding difficulties
Long-term health problems in menopause
Cardiovascular disease: loss of estrogen protective effect on vasculature and lipid profile
Postmenopausal osteoporosis: loss of estrogen causing compromised bone strength, fractures
Musculoskeletal degeneration: Laxity of soft tissue, poor muscular strength, Backache, joint pains
Dementia, cognitive decline
WHO criteria for osteoporosis severity
Name 1 clinical tool for fracture risk assessment
BMC or BMD below the young adult mean for women by:
Normal <1 SD
Low bone mass 1-2.5 SD
Osteoporosis >2.5 SD
Severe osteoporosis >2.5 SD And the presence of >1 fragility fractures
FRAX tool – takes other risk factors of fracture into account in clinical management
Clinical definition for diagnosis of menopause
Any tests for onset of menopause?
Clinical diagnosis in healthy women >45 years who have amenorrhoea for 12 months
Tests:
No biological marker
High FSH for some years before menopause
General lifestyle management for menopause
Lifestyle modification Smoking cessation Air conditioning Dress in layers Avoid alcohol and spicy food Reduce obesity Reduce stress (counseling)
Outline management plan for menopause
A. Lifestyle modification B. Cardiovascular risk assessment and management C. Cancer screening and prevention D. Hormone replacement therapy (HRT) E. Non-hormonal treatments for symptoms
Hormone replacement therapy (HRT) for menopause
- Benefits
- Risks
Benefits
Effective for severe climacteric symptoms
Slow progression of atrophic symptoms (topical oestrogen)
Prevent/ delay bone loss, lower risk of vertebral & non-vertebral fractures
Risks: Carcinoma of breast Venous thromboembolism Stroke Gallbladder disease
Hormone replacement therapy (HRT) for menopause
- Dosage
- Contraindications
Use lowest possible dose for shortest possible duration for symptom relief
Contraindications: Severe liver disease Oestrogen-dependent tumours e.g. breast, uterus Deep vein thrombosis, embolism Cerebrovascular disease Undiagnosed uterine bleeding
Regimens of Hormone replacement therapy (HRT) for menopause
With uterus: Oestrogen and progestogen (prevent endometrial hyperplasia/CA)
- Sequential (cyclical) – add Progestogen for 12-14 days/cycle for scheduled bleeding
- Continuous = non-bleeding regimen (suitable for >2 years post-menopause
Without uterus/ hysterectomy:
- Estrogen only
HRT for menopausal women
- Drug options
Oestrogen types:
1) Natural oestrogens (preferred):
- E.g. 17β-oestradiol (Estrofem®), conjugated equine estrogens (Premarin®)
- Preparation: oral, transdermal patch, gel Implant, vaginal ring
2) Phytoestrogens
Progestogen types:
1) Oral progestogen
2) Mirena® - levonorgestrel-releasing intrauterine system (IUCD)
Tibolone
- synthetic compound: converted to metabolites with oestrogenic, progestogenic actions
Definite benefit, risks of estrogen only HRT
Benefit - reduce hip fracture
Risk - Stroke
Neutral/ conflicting:
- Venous thromboembolism
- CRC
- CHD
- Invasive breast cancer
Definite benefit, risks of combination E+P HRT
Benefit:
- Reduce hip fracture
- Reduce CRC
Neutral
- Endometrial cancer
Risks:
- Invasive breast cancer
- Venous thromboembolism (VTE)
- Stroke
- Coronary heart disease (CHD) if administered after age 60-70
HRT for menopausal women
- Withdrawal method
- SIde effects
Withdrawal: Tapering vs. abrupt stop (no proven difference in clinical outcome)
Side effects: breast tenderness, fluid retention, bloating, nausea, headache, irregular bleeding
Outline non-hormonal treatments for vasomotor climacteric symptoms
Clonidine, gabapentin
Relaxation
Lifestyle modifications
non-hormonal treatments for psychological climacteric symptoms
Psychological counselling/ therapy
Anti-depressants
non-hormonal treatments for vaginal atrophy in climacteric symptoms
Lubricants, moisturisers
non-hormonal treatments for cardiovascular climacteric symptoms
Lifestyle:
Exercise
Avoid smoking
Control predisposing factors: HT, DM, hyperlipidaemia, obesity
non-hormonal treatments for osteroporosis after menopause
Lifestyle:
Calcium, vit D
Weight-bearing exercise
Avoid smoking/ excessive alcohol/ caffeine
Selective estrogen receptor modulator e.g. raloxifene
Bisphosphonates
RANK ligand (denosumab)
