Regulation of Female Fertility

Question 1

What are the primary causes of Amenorrhoea?

Answer 1

• Genitourinary abnormalities (for example, congenital absence of uterus, cervix or vagina eg Rokitansky syndrome or androgen insensitivity syndrome)
• Chromosomal abnormalities, eg turner’s syndrome
• Secondary hypogonadism (pituitary cause) eg, Kallmann syndrome, pituitary disease or hypothalamic amenorrhoea.

Question 2

What are some secondary causes of Amenorrhoea? Important card

Answer 2

• Uterine eg, Ashermans syndrome (adhesions)
• Ovarian eg, PCOS or premature ovarian failure,
• Pituitary eg Prolactinoma or pituitary tumour,
• Hypothalamic eg, weight loss, stress, or drugs

Question 3

What are some miscellaneous causes of amenorrhea

Answer 3

• Pregnancy or lactation,
• Iatrogenic,
• Thyroid dysfunction,
• Hyperandrogenism eg, Cushings, CAH or adrenal/ovarian tumour.

Question 4

What is the typical presentation of Polycystic ovarian disease?

Answer 4

• Anovulation (amenorrhoea, oligomenorrhoea or irregular cysts).
• Hyperandrogenism (hirsuitism, acne and alopecia)
• Raised testosterone and LH

Question 5

What factors are involved in the pathophysiology of PCOS?

Answer 5

• Abnormal gonadotrophins,
• Androgen excess
• Insulin resistance

Question 6

Explain the gonadotrophin levels seen in PCOS

Answer 6

• Increased LH concentration and/or increased LH receptors on ovaries. LH supports theca cells which increases ovarian androgen production.
• Decreased FSH levels at a low constant level (instead of normal fluctuations) which results in continuous stimulation of follicle’s without ovulation. Decreased conversion of androgens to oestrogens in granulosa cells.

Question 7

What androgens are seen to be increased in PCOS and where are these produced?

Answer 7

• DHEA (both ovary and adrenal glands but predominantly produced by adrenal gland),
• Androstenediol,
• Androstenedione (both ovary and adrenal gland - predominantly ovarian),
• Testosterone (both ovary and adrenal but predominantly ovary)
• Dihydrotestosterone (produced in periphery by conversion of testosterone)

Question 8

What are the precursors for testosterone?

Answer 8

• Androstenediol(produced from DHEA)
• Androstenedione (produced from DHEA)

Question 9

What happens to androgen levels in PCOS?

Answer 9

• There is increased androgen production from theca cells due to high LH,
• Disordered enzyme action
• Decreased sex hormone binding globulin (produced by liver), increasing amount of free testosterone - Only free testosterone is biologically active

Question 10

What are the features of insulin secretion/sensitivity in PCOS?

Answer 10

• Patients usually have excess insulin which causes insulin resistance and stimulates the theca cells to produce more testosterone and reduces liver production of SHBG. So there is more free testosterone

Question 11

What are the investigations for PCOS?

Answer 11

• Hormone profile for PCOS = High testosterone, high andrestenediol, high DHEA, high LH, low SHBG, low FSH.
• Assess for type 2 diabetes
• Exclude other pathologies

Question 12

What is the treatment for PCOS

Answer 12

• Combined oral contraceptive pill (Dianette) to regulate periods.
• Corticosteroids in severe hyperandrogenism to suppress adrenal androgen production.
• Spironolactone or cyproterone acetate which are androgen receptor antagonists,
• Finasteride (alpha reductase inhibitor) reduced peripheral conversion of testosterone.
• Weight loss!