Ovarian disorders Flashcards
Female gonadal axis
- Include kisspeptin
High oestrogen levels stimulates kisspeptin and KND-gamma neurones
- Stimulates the production of GnRH
When oestrogen not high:
GnRH stimulates LH and FSH production
- GnRH realised in a pulsatile fashion
FSH stimulates primary follicle granulosa cells—> stimulates oestrogen and inhibin
- Increase LH receptors
At high oestrogen levels, LH secretion due to increased GnRH pulsatility LH stimulates - Ovulation - Oocyte meiosis - Granulosa to luteal cell maturation
Diagnosis of ovulation
- Biochemistry
- Imaging
Biochemistry
- Day 21 progesterone blood test
LH detection kit
- Urinary
Imagining
- Transvaginal pelvic ultrasound [at day 10, follicle size measured]
Hypothalamic causes of ovulation problmes
Rare [genetic]
- Kiss1/ GnRH gene deficiency
Weight loss/ stress/ excessive exercise
Bulimia
Anorexia
Amennorhoea
Lack of periods for more than 6 months
Primary
- Never had a first period [menarche]
Secondary
- Had periods before
Oligomenorrhoea
Irregular periods- more than 6 weeks apart
Clinical features of PCOS
Hyperandrogenism
- Hirsutism, acne
Chronic oligomenorrhoea/ amenorrhoea
- Subfertility
Obesity/ Overweight [65-75%]
Diagnostic focus for PCOS
2/3 features:
- Polycystic ovaries
- Androgen excess
- Oligo/anovulation
USS appearance of polycystic ovaries
10 or more subcapsular follicles
- 2-8 mm in diameter
- In ovarian stroma [thickened]
Cysts are not required to have PCOS
Hormonal abnormalities that support diagnosis of PCOC
High LH, normal FSH
Increased androgens/ free testosterone
Decreased SHBG
Low/ normal oestrogen
SHBG
Sex hormone binding globulin
- produced by liver
Binds to testosterone and estradiol
- Makes testo inactive
- when levels decrease, there is more testosterone
Pathophysiology
Insulin resistance
- Inhibits FSH action of granulosa cells
- Increases androgens production from theca cells
- Decreases SHBG in liver cells
PCOS and endometrial cancer
Increases risk of endometrial hyperplasia and cancer
- Due to lack of progesterone action
Promotes hyperplasia
Increased risk with gestational DM and T2 DM
Lifestyle treatment of PCOS
Diet/ exercise
Smoking cessation
Maintain normal weight
COCP and PCOS
- Benefits
- Adverse effects
Increases SHBG
- Decreases free testosterone
Increased oestrogen and progesterone
- Decreases FSH and LH
Regulates menstrual cycle- prevents endometrial hyperplasia
Adverse effects: can exacerbate metabolic syndrome risk factors
- Weight gain
- Venous thrombosis
Cyproterone acetate
- Administration
- Drug type
- Mechanism
Anti-androgen used to treat PCOS
- Taken orally
Inhibits testosterone and 5-alpha DHEA to androgen receptor
Spironolactone
- Drug type
- Administration
- Mechanism
Mineralocorticoid receptor antagonist.
Anti-androgen effect
- Androgen receptor antagonist [inhibits TESTO and dihydrotestosterone binding]
- Useful in treating PCOS
Metformin and PCOS
Used to control insulin resistance
- Especially useful for obese patients
Hair removal and PCOS
To treat hirsutism
Photoepilation/ electrolysis
Eflornithine cream
Hirsutism differential diagnosis
95%
- PCOS
- Idiopathic
Non classical congenital adrenal hyperplasia
Cushing’s
Adrenal/ ovarian tumour
Severe complications of PCOS
Sudden onset
Virilisation
Cushings’
Primary ovarian insufficiency
- Presentation
Primary/ secondary amenorrhea
Includes premature menopause
Can present with hot flushes/ sweats, symptoms of menopause
- Secondary amenorrhoea
Primary ovarian insufficiency
- Aetiology
Autoimmunity
- Association with other autoimmune endocrine conditions
X chromosome abnormalities
- Turner syndrome
- Fragile X
Genetic predisposition
Iatrogenic
- Surgery
- Radiotherapy
- Chemotherapy
Investigations : Primary ovarian insufficiency
LH and FSH levels [will be high]
Karyotype
- Turner’s syndrome?
Pelvic USS?
Screen for other AI endocrine conditions
Treatment of POI
Psychological support
HRT
- Until 52
Monitor bone density
- DEXA scan
IVF
Turner syndrome
- Description
- Prevalence
Complete/ partial X monosomy
- Can be in some or all cells
Occurs in 1:2000/2500 females
Turner syndrome
- Presentation
Neonate
- Screening
Child/ adolescence
- Short stature
Adult
- Amenorrhoea
Congenital adrenal hyperplasia
- Aetiology
- Diagnosis
Disruption in cortisol biosynthesis disorder
- 21 alpha hydroxylase enzyme commonly affected
- Causes possible deficiency in cortisol/ aldosterone
- Leads to androgen excess
Measure 17-hydroxyprogesterone
- Confirmed with synACTHen test
21 hydroxylase deficiency
Causes cortisol deficiency
- Raised CRH and ACTH= excess androgen production
Congenital adrenal hyperplasia
- Presentation
Childhood
- Salt wasting [2/3]
- Virilisation [ambiguous in girls]
- Precocious puberty
- Abnormal growth
Adulthood [similar to PCOS]
- Hirsutism
- Oligo/ amenorrhoea
- Acne
- Subfertility
CAH treatment
Glucocorticoid and mineralocorticoid replacement
- Suppresses CRH, ACTH
Supraphysiological dose
- Suppresses adrenal androgen
- But growth has to be monitored in childhood
Surgery
- Manages ambiguous genitalia
Non-classical CAH [adult]
- Can treat as PCOS with COCP/ antiandrogen
Pituitary causes of ovulation problems
Anything that inhibits FSH/ LH
- Pituitary tumours
- Post-surgical
- Radiotherapy
Ovarian cause of ovulation problems
Premature ovarian insufficiency
Polycystic ovarian syndrome [most common]
Polymenorrhoea
Having periods that are less than 3 weeks apart
Hirsutism
Excess body hair in a male distribution
Androgen-dependant
- Endocrine abnormality
Hypertrichosis
- Familial/ ethnicity
PCOS and metabolic syndrome
Insulin resistance
- Increases androgen production in ovarian theca cells–> inhibits LH
- Increases SHBG in liver
- Decreased FSH–> prevents maturation of follicles
Impaired glucose
- Increases risk of gestational/ T2 DM
Dyslipidaemia
Vascular dysfunction
Reproductive effects of PCOS
Increased risk of miscarriages
Increased risk of gestational diabetes
Infertility linked to lack of ovulation is most likely because of PCOS
Turner syndrome associated problems
Short stature
CV problems
- Coarctation of aorta
- Bicuspid aortic valve
- Aortic dissection
- Hypertension
Renal
- Congenital abnormalities
Hypothyroid
Hearing probelms
Oestoporosis
Hirsutism differential diagnosis
PCOS/ idiopathic
Congenital adrenal hyperplasia
Cushing’s
Adrenal/ ovarian tumour
Virilisation
When women develop male-pattern hair growth and other masculine physical traits
Includes
- Frontal balding
- Deepening of voice
- Male-type muscle mass
- Clitoromegaly
