Disorders of ovulation Flashcards by Holly O'Flanagan

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

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FSH action

Causes the follicle to produce oestrogen and inhibin

Both negatively feedback on the hypothalamus and pituitary to decrease FSH

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Rising oestrogen levels cause

Kisspeptin and KNDy neurones to stimulate GnRH to produce LH in pulsatile fashion

Triggers ovulation

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Diagnosis of ovulation: clinical

Take a history from the woman

Regular menstraution usually 28 days

Mid cycle pain at ovulation

Vaginal discharge alters

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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

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Causes of ovulation problems: hypothalamus

Kiss1 gene deficiency- rare

GnRH deficiency- rare

Weight loss/ stress related/ excessive exercise

Anorexia/ bulimia

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Causes of ovulation: pituitary

Pituitary tumours (prolactinoma/ other tumours)

Post pituitary surgery/ radiotherapy

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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

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Amenorrhoea

Lack of period for more than 6 months

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Primary amenorrhoea

Never had a period (never went through menarche)

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Secondary amenorrhoea

Has menstruated before

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Oligomenorrhoea

Irregular periods

Usually occuring more than 6 weeks apart

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Polymenorrhoea

Periods occuring less than 3 weeks apart

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Androgen dependent hirsutism

Excess body hair in a male distribution

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Clinical features of POCS

Hyperandrogenism
- hirsutism, acne

Chronic oligomenorrhoea/ amenorrhoea

<9 periods/ year
subfertility

Obesity (but 25% of women with PCOS are lean)

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Elements in the diagnosis of PCOS

Polycystic ovaries

Andorgen excess

Oligo/ anovulation

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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