Disorders of ovulation Flashcards
First step in ovulation
Starts at the hypothalamus with the supra chiasmic nucleus
Interacts with the kisspeptin neurones and the KNDy neurones
Kisspeptin neurones in the arcuate nucleus and anteroventral peri ventricular area
Kisspeptin and KNDy are potent stimulators of GnRH
FSH action
Causes the follicle to produce oestrogen and inhibin
Both negatively feedback on the hypothalamus and pituitary to decrease FSH
Rising oestrogen levels cause
Kisspeptin and KNDy neurones to stimulate GnRH to produce LH in pulsatile fashion
Triggers ovulation
Diagnosis of ovulation: clinical
Take a history from the woman
Regular menstraution usually 28 days
Mid cycle pain at ovulation
Vaginal discharge alters
Diagnosis of ovulation: biochemistry
Day 21 progesterone blood test (7 days before start of next menstrual period
LH detection kits: urinary kits bought over the counter
Transvaginal pelvic ultrasound done from day 10
Causes of ovulation problems: hypothalamus
Kiss1 gene deficiency- rare
GnRH deficiency- rare
Weight loss/ stress related/ excessive exercise
Anorexia/ bulimia
Causes of ovulation: pituitary
Pituitary tumours (prolactinoma/ other tumours)
Post pituitary surgery/ radiotherapy
Causes of ovulation: ovary
Premature ovarian insufficiency
- developmental or genetic causes e.g. Turner’s syndrome
- autoimmune damage and destruction of ovaries
- cytotoxic and radiotherapy
- surgery
Polycystic ovarian syndrome: commonest cause
Amenorrhoea
Lack of period for more than 6 months
Primary amenorrhoea
Never had a period (never went through menarche)
Secondary amenorrhoea
Has menstruated before
Oligomenorrhoea
Irregular periods
Usually occuring more than 6 weeks apart
Polymenorrhoea
Periods occuring less than 3 weeks apart
Androgen dependent hirsutism
Excess body hair in a male distribution
Clinical features of POCS
Hyperandrogenism
- hirsutism, acne
Chronic oligomenorrhoea/ amenorrhoea
- <9 periods/ year
- subfertility
Obesity (but 25% of women with PCOS are lean)
Elements in the diagnosis of PCOS
Polycystic ovaries
Andorgen excess
Oligo/ anovulation
PCOS and the metabolic syndrome
Insulin resistance with increase insulin
- increase androgen production by ovarian theca cells
- decreased SHBG production by the liver
Impaired glucose tolerance
- increase risk gestational DM and T2 DM
Dyslipidaemia
Vascular dysfunction
Increase risk CVD
Hormonal abnormalities in PCOS
Raised baseline LH and normal FSH levels
Raised androgens and free testosterone
Reduced sex hormone binding globuln
Oestrogen usually low but can be normal
Sex hormone binding globulin
Produced by the liver
Binds testosterone and oestradiol
If testosterone bound, not converted to active component dihydrotestosterone
SHBG increased by oestrogens
SHBG decreased by testosterone so released more free testosterone
Reproductive effects of PCOS
Maybe associated with varying degrees of infertility
15% of all causes of infertility is lack of ovulation
80% of lack of ovulation due to PCOS
Associated with increased miscarriages
Increased risk of gestational diabetes
PCOS and endometrial cancer
Increased endometrial hyperplasia and cancer
Lack of progesterone on the endometrium
Endometrial cancer associated with type 2 diabetes and obesity
Treatment of PCOS: lifestyle modification
Diet and exercise Stop smoking - decrease insulin resistance - increase [SHBG] - decrease [free testo] - improved fertility - improved metabolic syndrome
High frequency eating disorders
- bulimia associated with PCOS
Lean women with PCOS should try not to get fat
Combined oral contraceptive
Increases SHBG and thus decreases free testosterone
Decreases FSH and LH and therefore ovarian stimulation
Regulates cycle and decreases endometrial hyperplasia
May cause weight gain, venous thrombosis, adverse effects on metabolic risk factors
Anti-androgens
With COCOP/ other form of secure contraception
Cyproterone acetate (oral tablet) - inhibits binding of testosterone and 5 alpha dihydrotestosterone to androgen receptors
Sprionolactone (oral tablet)
- anti mineralocorticoid and anti androgen properties
Hair removal
Photoepilation (laser)/ electrolysis
Eflornithine cream (non NHS) - inhibits ornithine decarboxylase enzyme in hair follicles
Targeting insulin resistance in PCOS: metformin
Decrease insulin resistance, decrease insulin levels, decrease ovarian androgen production
May help with weight loss/ diabetes prevention
May increase ovulation (with clomifene), safe in pregnancy
Less helpful for hirsutism and oligomenorrhoea, but may be an option for obese PCOS women
Primary ovarian insufficiency: presentation
Primary or secondary amenorrhoea
Secondary amenorrhoea may be associated with hot flushes and sweats
Primary ovarian insufficiency: aetiology
Autoimmunity
- may be associated with other autoimmune endocrine conditions
X chromosomal abnormalities
- turner syndrome
- fragile X associated
Genetic predisposition
- premature menopause
Iatrogenic
- surgery, radiotherapy, chemotherapy
Premature ovarian failure: investigations
History. examination
Increase LH and FSH
Karyotype
Consider pelvic USS
Consider screening for other autoimmune endocrine disease
- thyroid function tests, glucose, cortisol
Premature ovarian failure: management
Psychological support
HRT
- continue till around 52
Monitor bone density
- DEXA scan
Fertility
- IVF with donor egg
Turner syndrome
Complete/ partial X monosomy in some/ all cells
- 50% of cases will be XO
- rest: partial absence of mosaicism
1:2000 - 1:2500 live born girls
Turner syndrome presentation
May be diagnosed in the neonate
May present with short stature in childhood
May present with primary/ secondary amenorrhoea
Turner syndrome associated problems
Short stature
- consider GH treatment
CV system
- coarctation of aorta
- bicuspid aortic valve
- aortic dissection
- hypertension
Renal
- congenital abnormalities
Metabolic syndrome
Hypothyroidism
Ears/ hearing problems
Osteoporosis
Differential diagnosis of hirsutism
95% PCOS or idiopathic hirsutism
1% non classical congenital adrenal hyperplasia (CAH)
1% Cushing’s syndrome
1% adrenal/ ovarian tumour
When to worry
Sudden onset of severe symptoms
Virilisation
- frontal balding
- deepening of voice
- male type muscle mass
- clitoromegaly
Possible Cushing’s syndrome
Congenital adrenal hyperplasia
Disorders of cortisol biosynthesis
- carrier frequency 1:60
- most patients are compound heterozygotes
95% CAH caused by 21-hydroxylase deficiency
- cortisol deficiency
- may have aldosterone deficiency
- androgen excess
- depends on degree of enzyme deficiency
CAH childhood
Classic/ severe
Salt losing (2/3rd)
Non salt losing (1/3rd)
Simple virilising
CAH adulthood
Non classic/ mild
Late onset
CAH childhood presentation
Salt wasting
- hypovolaemia, shock
Virilisation
- ambiguous genitalia in girls
- early virilisation in boys
Precocious puberty
Abnormal growth
- accelerated early
- premature fusion
CAH adulthood presentation
Hirsutism
Oligo/ amenorrhoea
Acne
Subfertility
Similar presentation to PCOS
CAH treatment
Glucorticoid and mineralocorticoid replacement
Glucocorticoid suppress CRH/ ACTH
Supraphysiological glucocorticoid doses may be needed to suppress andrenal androgen production
Surgical management for ambiguous genitalia
Non classical CAH in adult women
