Sex hormone binding globulin - produced by liver Binds to testosterone and estradiol - Makes testo inactive - when levels decrease, there is more testosterone

Insulin resistance - Inhibits FSH action of granulosa cells - Increases androgens production from theca cells - Decreases SHBG in liver cells

Spironolactone - Drug type - Administration - Mechanism

Mineralocorticoid receptor antagonist. Anti-androgen effect - Androgen receptor antagonist [inhibits TESTO and dihydrotestosterone binding] - Useful in treating PCOS

Ovarian disorders Flashcards by aderonke adesanoye

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

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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]

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Hypothalamic causes of ovulation problmes

Rare [genetic]
- Kiss1/ GnRH gene deficiency

Weight loss/ stress/ excessive exercise

Bulimia

Anorexia

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Amennorhoea

Lack of periods for more than 6 months

Primary
- Never had a first period [menarche]

Secondary
- Had periods before

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Oligomenorrhoea

Irregular periods- more than 6 weeks apart

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Clinical features of PCOS

Hyperandrogenism
- Hirsutism, acne

Chronic oligomenorrhoea/ amenorrhoea
- Subfertility

Obesity/ Overweight [65-75%]

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Diagnostic focus for PCOS

2/3 features:

Polycystic ovaries
Androgen excess
Oligo/anovulation

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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

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Hormonal abnormalities that support diagnosis of PCOC

High LH, normal FSH

Increased androgens/ free testosterone

Decreased SHBG

Low/ normal oestrogen

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SHBG

Sex hormone binding globulin
- produced by liver

Binds to testosterone and estradiol

Makes testo inactive
when levels decrease, there is more testosterone

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Pathophysiology

Insulin resistance

Inhibits FSH action of granulosa cells
Increases androgens production from theca cells
Decreases SHBG in liver cells

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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

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Lifestyle treatment of PCOS

Diet/ exercise

Smoking cessation

Maintain normal weight

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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

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Cyproterone acetate

Administration
Drug type
Mechanism

Anti-androgen used to treat PCOS
- Taken orally

Inhibits testosterone and 5-alpha DHEA to androgen receptor

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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