Amenorrhoea Flashcards
What is the definition of amenorrhoea?
Failure of menstruation to occur at the expected time
What are the 2 categories of amenorrhoea?
- Primary amenorrhoea
- Secondary amenorrhoea
What is primary amenorrhoea?
Menstruation has never occurred - failure to menstruate by age of 16 in females
What is the definition of secondary amenorrhoea?
Established menstruation ceases for 6 months or more
What key feature helps determine the likely cause of primary amenorrhoea?
if secondary sexual characteristics are present or not
If secondary sexual characteristics are absent in primary amenorrhoea, what is the likely cause?
delayed puberty
What type of cause should be suspected in primary amenorrhoea when pubertal development is otherwise normal?
Anatomical cause
What are the 2 key anatomical causes of primary amenorrhoea?
- Congenital absence of uterus - failure of Müllerian ducts to develop
- Imperforate hymen
What causes congenital absence of the uterus?
failure of Müllerian ducts to develop
What is meant by imperforate hymen?
menstrual blood is retained within the vagina (a haematocolpos) causing cyclical lower abdominal pain each month at the time of menstruation (cryptomenorrhoea)
What is the term given to menstrual blood retained in the vagina in the case of imperforate hymen?
haematocolpos
What key symptom, in addition to absence of periods, will there be in primary amenorrhoea caused by imperforate hymen?
cyclical lower abdominal pain each month at the time of menstruation - cryptomenorrhoea
What will be present on inspection in primary amenorrhoea due to an imperforate hymen?
Distended hymenal membrane through which dark blood may be seen
What is the management of imperforate hymen?
Incision, usually under anaesthesia
In addition to anatomical and sexual development pathology, what else could cause failure to menstruate?
physiological delay - development normal, but inherent delay in onset of menstruation
What is common in the history of a patient with physiological delay in onset of menstruation?
family history of same delay in mother
What test is useful to identify constitutional menstrual delay?
Progestogen challenge test: progestogen e.g. medroxyprogesterone acetate is given orally for 5 days, and if endometrium has been stimulation from endogenous oestradiol then withdrawal of progestogen should lead to a vaginal bleed
If bleed occurs, offer reassurance that spontaneous menstruation likely to occur
In addition to the diagnostic test for constitutional delay in onset of menstruation what other test can be useful?
In addition to progestogen challenge test, abdominal ultrasound may be used to confirm uterus and ovaries normal
What are 6 groups of causes of primary amenorrhoea that are not structural?
- Chromosomal
- Hypothalamic
- Pituitary
- Ovarian
- Other endocrine
- Uterine / vaginal
What are 3 chromosomal causes of primary amenorrhoea?
- XO - Turner syndrome
- 46, XY disorders of sex development (DSD)
- Ovotesticular DSD
What are 5 hypothalamic causes of primary amenorrhoea?
- Physiological delay
- Weight loss/ anorexia/ heavy exercise
- Isolated GnRH deficiency
- Congenital central nervous system (CNS) defects
- Intracranial tumours
What are 5 pituitary causes of primary amenorrhoea?
- Partial/ total hypopituitarism
- Hyperprolactinaemia
- Pituitary adenoma
- Empty sella syndrome
- Trauma/ surgery
What are 5 ovarian causes of primary amenorrhoea?
- True agenesis
- Premature ovarian failure
- Radiation/ chemotherapy/ autoimmune
- Polycystic ovaries
- Virilising ovarian tumours
What are 3 other endocrine causes of primary amenorrhoea?
- Primary hypothyroidism
- Adrenal hyperplasia
- Adrenal tumour
What are 2 uterine/ vaginal causes of primary amenorrhoea (structural causes)?
- Imperorate hymen
- Uterovaginal agenesis
What are the 3 most common clinical causes of secondary amenorrhoea?
- Weight loss
- Polycystic ovary syndrome (PCOS)
- Hyperprolactinaemia
What are 6 groups of causes of secondary amenorrhoea?
- Physiological
- Hypothalamic
- Pituitary
- Ovarian
- Other endocrine
- Uterine/ vaginal
What are 3 physiological causes of secondary amenorrhoea?
- Pregnancy
- Lactation
- Menopause
What are 3 hypothalamic causes of secondary amenorrhoea?
- Weight loss/ anorexia
- Heavy exercise
- Stress
What are 3 pituitary causes of secondary amenorrhoea?
- Hyperprolactinaemia
- Partial/ total hypopituitarism
- Trauma/ surgery
What are 5 ovarian causes of secondary amenorrhoea?
- Polycystic ovarian syndrome
- Premature ovarian failure
- Surgery/ radiotherapy/ chemotherapy
- Resistant ovary syndrome
- Virislising ovarian tumours
What are 4 uterine/ vaginal causes of secondary amenorrhoea?
- Surgery - hysterectomy
- Endometrial ablation
- Progestogen intrauterine device
- Asherman syndrome
What physiological cause must be excluded in all sexually active women presenting with amenorrhoea?
Pregnancy (and lactation)
What causes secondary amenorrhoea during breastfeeding?
high postpartum level of prolactin associated with breastfeeding - suppresses ovulation and gives rise to lactational amenorrhoea
What can cause amenorrhoea to persist during breastfeeding?
persists throughout time infant fully breastfed, but with introduction of supplementary feeding and subsequent reduction in frequency of suckling, prolactin levels fall and ovarian activity resumed
What can occur as a result of high levels of prolactin during breastfeeding?
hypo-oestrogenic state which can lead to atrophic vaginitis and occasionally painful intercourse - prolactin exerts antagonistic action of oestrogen production
What is the name given to refer to hypothalamic amenorrhoea?
hypogonadotrophic hypogonadism
What is usually the cause of hypogonadotrophic hypogonadism leading to amenorrhoea?
stress
What is usually the outcome of stress-induced hypogonadotrophic hypogonadism and amenorrhoea?
usually resolves spontaneously
What can cause secondary amenorrhoea in physical stress e.g. due to athletic training?
suppression of hypothalamo-pituitary-ovarian axis due to physical stress - low levels of pituitary gonadotrophins in association with low levels of prolactin and oestradiol
What level of weight loss may result in secondary amenorrhoea?
change in body weight to only 10-15% below the ideal
What should you consider when weight loss is associated with secondary amenorrhoea?
anorexia nervosa
What can restore ovulatory function following secondary amenorrhoea due to weight loss?
Restoration of body weight - may be significant time interval between attainment of ideal body weight and resumption of ovarian activity
Why is ovulation induction therapy not recommended in cases of weight-loss induced secondary amenorrhoea until normal weight is restored?
not recommended until restoration of body weight as pregnancy, if it occurs, carries risk of growth restriction of fetus and increased perinatal mortality
If hypothalamic amenorrhoea is not related to low body weight, what does treatment for it depend on?
whether or not woman wants to conceive
In the case of hypothalamic secondary amenorrhoea, what is the treatment of choice for women who do not want to conceive?
oestrogen replacement therapy - oral contraceptive pill
In the case of hypothalamic secondary amenorrhoea, what is the treatment of choice for women who do want to conceive? 2 options
- Ovulation may be induced with pulsatile GnRH therapy OR
- Exogenous gonadotrophins
What is the effect of prolactin in the body?
stimulates breast development and subsequent lactation
What other hormone influences the secretion of prolactin and how?
Inhibited by dopamine from hypothalamus
What type of hormone is prolactin and where is it produced from?
Polypeptide hormone produced by lactotrophs of anterior pituitary
What is the action of prolactin on other hormones?
suppresses ovarian activity by interfering with secretion of gonadotrophins
What can cause mildly elevated prolactin levels?
common, can be due to stress e.g. of venepuncture
What are 2 key effects of sustained higher levels of prolactin?
- Amenorrhoea
- Galactorrhoea unrelated to pregnancy
In what proportion of patients with hyperprolactinaemia does galactorrhoea occur?
<50%
What proportion of patients with galactorrhoea have an elevated prolactin level?
<50%
What are 2 groups of causes of hyperprolactinaemia?
- Pituitary adenoma
- Secondary to other causes
What are 2 types of pituitary adenomas which can cause hyperprolactinaemia?
- Microadenoma
- Macroadenoma
What are 6 causes of hyperprolactinaemia that are secondary to causes other than pituitary adenoma?
- Primary hypothyroidism
- Chronic renal failure
- Pituitary stalk compression
- Polycystic ovarian syndrome
- Drugs (phenothiazines, haloperidol, metoclopramide, cimetidine, methyldopa, antihistamines, morphine)
- Idiopathic
What are 7 drug causes of hyperprolactinaemia?
- Phenothiazines
- Haloperidol
- Metoclopramide
- Cimetidine (histamine H2-receptor antagonist)
- Methyldopa
- Antihistamines
- Morphine
Where in the anterior pituitary do adenomas occur (that can cause hyperprolactinaemia)?
lateral wings
At what level of hyperprolactinaemia is imaging performed to investigate for a potential pituitary adenoma and what imaging is performed?
- prolactin >1000 mU/L
- CT or ideally MRI
What defines the difference between micro and macroadenoma for pituitary tumours?
microadenoma is <10mm and macro is >10mm
What should you check in examination in suspected pituitary adenoma which may cause secondary amenorrhoea?
visual fields checked - optic chiasm compression may lead to bitemporal hemianopia
What is the typical prognosis of pituitary adenomas?
- 1/3 regress spontaneously
- <5% of microadenomas become macroadenomas
What do serum levels of hyperprolactinaemia correlate with in pituitary adenoma?
tumour size
What should you suspect if a tumour appears relatively large and prolactin level is only modestly elevated?
pituitary stalk compression from nonsecreting macroadenoma or other tumour (e.g. craniopharyngioma) is possible
What is a possible cause of apparently idiopathic hyperprolactinaemia?
microadenomas too small to be picked up by MRI scan
What should be performed for all patients with pituitary adenoma before treatment?
pituitary imaging
What are 2 types of management for pituitary adenoma that may be causing hyperprolactinaemia (causing secondary amenorrhoea)?
- Dopamine agonist - bromocriptine or cabergoline
- Transnasal transsphenoidal microsurgical excision of adenoma
What is the most common management of pituitary adenoma?
Dopamine agonist (bromocriptine or cabergoline) - transnasal transphenoidal excision only rarely required
What are the 2 types of dopamine agonist which can be used to treat pituitary adenoma causing hyperprolactinaemia?
Bromocriptine or cabergoline
What is meant by the term premature ovarian failure?
Cessation of ovarian function before age of 40. Failure is due to depletion of primordial follicles in the ovaries
How common is premature ovarian failure?
1% of women
What are 6 causes of premature ovarian failure?
- Surgery
- Viral infections e.g. mumps
- Cytotoxic drugs
- Radiotherapy
- Idiopathic
- Chromosomal abnormality - XO mosaicism or XXX
What are 3 poor prognostic signs for recovery from premature ovarian failure?
- Low oestradiol level
- Very high FSH
- Absence of any menstrual activity
What are 2 elements of treatments for premature ovarian failure?
- Pregnancy by in vitro fertilisation with donor oocytes may be possible
- Hormone replacement therapy - to relieve postmenopausal symptoms, minimise osteoporosis risk
What is premature ovarian failure sometimes associated with?
other autoimmune disorders
Waht are 2 reasons why hormone replacement therapy is given in premature ovarian failure?
- Relieve postmenopausal symptoms
- Minimise risk of osteoporosis
What is the most common form of anovulatory infertility?
Polycystic ovary syndrome
What proportion of women are believed to be affected by PCOS?
20%
What are the criteria for diagnosis of polycystic ovary syndrome?
at least 2 out of the following 3: (Rotterdam)
- oligomenorrhoea or amenorrhoea
- ultrasound appearane of large-volume ovaries (>10cm3) and/or multiple small follicles (12 or more <10mm)
- Clinical evidence of excess androgens (acne, hirsutism) or biochemical evidence (raised testosterone)
What is thought to be the principal underlying disorder of PCOS?
insulin resistance, with resultant hyperinsulinaemia stimulating excess ovarian androgen production
thought to be systemic metabolic condition (rather than primary gynaecological)
What are 3 associations of PCOS?
- Dyslipidaemia
- Predisposition to non-insulin-dependent diabetes
- Predisposition to cardiovascular disease
What does the treatment of PCOS depend on?
whether presenting problem is menstrual irregularity, hirsutism or infertility
What treatment is available for PCOS where irregular menses is the primary problem?
COCP to regulate menses
How can PCOS be treated if the primary problem is hirsutism? 3 ways
- cosmetic measures such as waxing or laser treatment
- with COCP as suppresses ovarian androgen production
- with the antiandrogen cyproterone acetate
What must be remembered in women who are taken an antiandrogen (e.g. cyproterone acetate) who have PCOS and why?
must use effective contraception during, and for at least 3 months after, treatment - potential risk of teratogenicity (feminisation of male fetus) with antiandrogen therapy
What is used to treat women with PCOS where infertility is the primary problem? 3 options
- Clomifene - to induce ovulation in women with anovulatory infertility
- Gonadotrophin injections if clomifene doesn’t work
- Laproscopic laser or diathermy to the ovary
What is clomifene?
oral ovulatory stimulant - acts as selective oestrogen receptor modulator (SERM)
What is the cornerstone of management of PCOS for all presenting complaints?
weight reduction - reduces insulin resistance, corrects hormone imbalance, promotes ovulation
What is the role of insulin-sensitising agents e.g. metformin to treat PCOS?
larger trials have failed to demonstrate benefit
In addition to treating symptoms and weight loss in PCOS, what is another key aspect of the management of these patients?
Screening of cardiovasuclar risk factrs - HTN and glucose intolerance
Screening for endometrial hyperplasia and endometrial carcinoma
Why is there increased risk of endometrial hyperplasia/ carcinoma in PCOS?
consequence of effects of anovulation with unopposed oestrogen stimulation of the endometrium
What are 4 other endocrine causes of secondary amenorrhoea?
- Thyrotoxicosis
- Primary hypothyroidism
- Late-onset congenital adrenal hyperplasia
- Androgen-secreting adrenal tumours
Why can primary hypothyroidism cause secondary amenorrhoea?
thyrotrophin-releasing hormone (TRH, secreted by hypothalamus) also stimulates prolactin secretion
What usually causes late-onset congenital adrenal hyperplasia?
Deficiency of enzyme 21-hydroxylase
What is usually the management of late-onset adrenal hyperplasia, a cause of secondary amenorrhoea?
low dose corticosteroids to re-etsablish ovulatory function by suppressing adrenal function
What are 2 causes of Asherman syndrome, a uterine cause of secondary amenorrhoea?
- Excessive uterine currettage
- Severe postpartum infection
What is the treatment of Asherman’s syndrome?
breaking down adhesions through hysteroscope with or without inserting intrauterine contraceptive device to deter reformation
What is Asherman’s syndrome?
adhesions in the uterine cavity form that are so severe they obstruct menstrual flow
How can excessive uterine curettage come about and cause Asherman’s syndrome?
usually at time of miscarriage, termination of pregnancy or secondary PPH - may remove basal layer of endometrium and result in uterine adhesions (synechiae)
What are the 7 aspects of clinical management for all types of amenorrhoea?
- Exclude pregnancy
- Ask about perimenopausal symptoms (flushing, vaginal dryness)
- History - weight changes, drugs, medical disorders, thyroid symptoms
- Examination - height, weight, visual fields, hirsutism, virilisation, pelvic exam
- Serum LH, FSH, prolactin, testosterone, thyroxine, TSH
- Transvaginal ultrasound scan - polycystic ovaries
- Review with the results
What are 4 key things to ask about in the history for amenorrhoea?
- Weight changes
- Drugs
- Medical disorders
- Thyroid symptoms
What are 5 key things to do in the examination for amenorrheic patients?
- Height
- Weight
- Visual fields
- Hirsutism/ virilisation
- Pelvic examination
What are 6 blood tests to perform in amenorrhoea?
- FSH
- LH
- Prolactin
- Testosterone
- Thyroxine
- TSH
What criterion is required to make a diagnosis of hyperprolactinaemia?
Prolactin >1000mU/L on at least 2 occasions
If FSH is elevated what is the management?
if >30U/L, repeat 6 week later. If still elevated and patient >40 years, patient is menopausal. If <40, diagnosis is premature ovarian failure
Consider HRT. Pregnancy with oocyte donation possible
What is the usual management of patients with idiopathic amenorrhoea?
anti-oestrogen e.g. clomifene - usually respond well
