Endocrine Disorders Affecting Reproduction

Question 1

What are the key hormones in the reproductive pathway?

Answer 1

Follicle stimulating hormone (FSH) stimulates follicles to grow and produce oestrogen. Leutinising hormone (LH) acts on thecal cells primarily which produce androgens, leading to ovulation

Question 2

In what manner is GnRH released?

Answer 2

GnRH is released in a pulsatile manner, causing pulsatile LH release.

Question 3

What happens if you give continuous GnRH?

Answer 3

Continuous GnRH will eventually suppress LH and FSH. This is used in IVF to control the cycle and growth of multiple follicles without the risk of spontaneous ovulation.

Question 4

What can go wrong with the hypothalamo-pituitary-gonadal axis?

Answer 4

1. Central pathology: Lack of secretion of LH and FSH due to hypothalamic/pituitary disease. 2. Gonadal damage: Failure of germ cell production and lack of sex steroid production. 3. Polycystic ovary syndrome: Normal hormone levels but not ovulating.

Question 5

How do HPG axis issues present in females?

Answer 5

Menstrual history is important: Oligoamenorrhoea, Amenorrhoea, Infertility, Oestrogen deficiency symptoms, Hirsutism, acne, androgenic alopecia, Weight gain/loss, Galactorrhoea.

Question 6

What are the causes of amenorrhoea?

Answer 6

Pregnancy, central causes (hypothalamic, pituitary), ovarian causes (Turner’s syndrome, premature ovarian failure), polycystic ovary syndrome, and miscellaneous causes (thyrotoxicosis, chronic disease).

Question 7

What is hypothalamic amenorrhoea?

Answer 7

It is caused by severe marked weight loss, exercise, or bulimia, leading to pituitary gland dysfunction.

Question 8

What is congenital leptin deficiency?

Answer 8

Leptin deficiency affects food intake and reproductive system functioning, leading to severe obesity, hyperphagia, and hypogonadotropic hypogonadism.

Question 9

What are the main anterior pituitary hormones?

Answer 9

ACTH (adrenal cortex regulation), TSH (thyroid hormone regulation), GH (growth), LH/FSH (reproductive control), PRL (prolactin for breast milk production).

Question 10

How is PRL secretion controlled?

Answer 10

PRL is synthesized in lactotrophs and is regulated by dopamine, which inhibits its release. Disruption of dopamine can lead to lactation.

Question 11

What causes physiological hyperprolactinaemia?

Answer 11

Stress results in excess PRL release, which is more common in women and rarely exceeds 850-1000 mU/L.

Question 12

What are the clinical features of hyperprolactinaemia?

Answer 12

In premenopausal women: hypogonadism, oligomenorrhoea, galactorrhoea. In postmenopausal women: usually none due to existing amenorrhoea.

Question 13

What are the causes of pathological hyperprolactinaemia?

Answer 13

PRL-secreting pituitary tumours (prolactinomas), loss of inhibitory effect from hypothalamus-derived dopamine, drugs (DA antagonists), and hypothyroidism.

Question 14

What does premature ovarian insufficiency usually present with?

Answer 14

Amenorrhoea, oestrogen deficiency, and elevated LH/FSH levels (>30 IU/L) in women under 45.

Question 15

What are the causes of premature ovarian insufficiency?

Answer 15

Congenital causes (Turner’s syndrome), autoimmune conditions, iatrogenic causes (chemotherapy, surgery), and genetic mutations.

Question 16

What are the phenotypes of Turner’s syndrome?

Answer 16

Short stature, low hairline, widely spaced nipples, webbed neck, nevi, small fingernails.

Question 17

How do autoimmune conditions lead to POI?

Answer 17

POI can be caused by autoimmune diseases such as Graves Disease, Addison’s, and diabetes, with 2-10% of cases linked to adrenal autoimmunity.

Question 18

What is the mechanism of autoimmune POI?

Answer 18

Inflammatory infiltration of follicles and production of anti-ovarian antibodies lead to apoptosis and atrophy.

Question 19

What is the link between Fragile X premutation and POI?

Answer 19

1/200 females have the genetic change leading to FXPOI, which accounts for about 4-6% of all POI cases. It is inherited in an X-linked dominant pattern.

Question 20

What is the management of POI?

Answer 20

Diagnosis on serial FSH and E2 levels, karyotyping, screening for autoimmune diseases, and managing with oestrogen replacement.

Question 21

What is Polycystic Ovary Syndrome (PCOS)?

Answer 21

The most common endocrine condition affecting 10% of pre-menopausal women, with an unknown aetiology possibly related to insulin sensitivity.

Question 22

What is PCOS associated with?

Answer 22

Oligoamenorrhoea, hirsutism, obesity, infertility, polycystic ovaries on ultrasound, and hyperandrogenism.

Question 23

What happens if you do not protect the endometrium from oestrogen exposure?

Answer 23

You get endometrial hyperplasia due to unopposed oestrogen exposure.

Question 24

What is the Rotterdam diagnostic criteria for PCOS?

Answer 24

2 out of 3: Oligo-/Amenorrhea, clinical or biochemical signs of hyperandrogenaemia, polycystic ovaries.

Question 25

What are the clinical features of PCOS?

Answer 25

PCO, acanthosis nigricans, insulin resistance, obesity, androgen excess, and anovulation.

Question 26

What is hirsutism?

Answer 26

Male hormone dependent hair growth in areas such as the upper lip, chin, and abdomen.

Question 27

What is Hirsutism?

Answer 27

Male hormone dependent hair growth.

Question 28

How is Hirsutism categorised?

Answer 28

Upper lip, chin, anterior neck, sideburn, breasts, pubic hair. A score >8 on the score of hirsutism indicates hirsutism.

Question 29

What is androgenic alopecia?

Answer 29

Male-pattern baldness that can also occur in females.

Question 30

What clinical problems arise with pregnant women with PCOS?

Answer 30

Oligo-/Amenorrhea & Infertility are the most common clinical problems. Risk of gestational diabetes and pregnancy-related hypertension is ten times increased due to insulin resistance.

Question 31

What is the IVF risk for pregnant women with PCOS?

Answer 31

Increased risk of Ovarian Hyperstimulation Syndrome (OHSS). Avoided by using an antagonist IVF protocol with a GnRH trigger injection for egg maturation.

Question 32

What risks can OHSS cause in a pregnant woman with PCOS?

Answer 32

Can cause fluid leaking into the 3rd space, dehydration, ascites, kidney problems, and high risk of venous thromboembolism.

Question 33

What can be treated in PCOS?

Answer 33

Obesity and Oligo/Amenorrhea can be treated with Metformin, lifestyle modification, and MPA (progesterone).

Question 34

What are the three types of anti-androgenic oral contraceptives?

Answer 34

Dianette, which is not recommended anymore due to increased risk of venous thromboembolism, and two others with specific anti-androgen progesterone.

Question 35

What is 21-hydroxylase deficiency?

Answer 35

Causes congenital adrenal hyperplasia and can mimic PCOS.

Question 36

What are the two forms of 21-hydroxylase deficiency?

Answer 36

Classical form (neonatal/infancy presentation) and Non-classical form (childhood/adult presentation).

Question 37

How do you test for 21-hydroxylase deficiency?

Answer 37

If 17 OHP is high, it indicates 21-hydroxylase deficiency.

Question 38

What is androgen insensitivity syndrome?

Answer 38

A spectrum of disorders due to mutations in the Androgen receptor, including Complete, Incomplete, and Reifensteins.

Question 39

What are the features of someone with androgen insensitivity syndrome?

Answer 39

Female external genitalia, short blind-ending vagina, no uterus, absent prostate, and gynaecomastia.

Question 40

What is 5a-reductase deficiency?

Answer 40

A condition where individuals appear female but are genetically male (46XY) and unable to convert Testosterone to DHT.

Question 41

How does hypogonadism present in males?

Answer 41

Delayed puberty, psychological effects, gynaecomastia, loss of body hair, decreased muscle mass, and infertility.

Question 42

What are the causes of hypogonadism I in males?

Answer 42

Primary gonadal failure due to trauma, chemotherapy, infections, and chromosomal abnormalities.

Question 43

What are the causes of hypogonadism II in males?

Answer 43

Secondary gonadal failure due to pituitary tumors, hyperprolactinaemia, and hypothalamic disorders.

Question 44

How is hypogonadism investigated?

Answer 44

Clinical examination, LH, FSH, Testosterone levels, and further investigations based on results.

Question 45

What is Klinefelter’s syndrome?

Answer 45

Affects 1:1000 males with a 47 XXY karyotype, leading to primary hypogonadism and feminisation.

Question 46

What is myotonic dystrophy?

Answer 46

An autosomal dominant condition that can cause progressive muscular weakness, myotonia, and primary gonadal failure.

Question 47

What is Kallman’s syndrome?

Answer 47

Idiopathic hypogonadotropic hypogonadism with anosmia in 75% of cases.

Question 48

How can testosterone be replaced?

Answer 48

Through tablets, buccal mucosa, injections, transdermal patches, or subdermal implants.

Question 49

What is androgen abuse?

Answer 49

The use of designer drugs that increase testosterone, leading to various health hazards.

Question 50

What are the causes of male infertility?

Answer 50

Endocrine causes are rare; assessment includes history, examination, and seminal fluid analysis.