Reproductive and Post-Reproductive

Question 1

Describe the common pathway got sex steroid hormone synthesis. (6)

Answer 1

Cholesterol > Pregnenolone > Progesterone > 17-hydroxyprogesterone > Testosterone > Oestradiol.

Question 2

Describe the receptors for sex steroid hormones. (3)

Answer 2

Nuclear receptors exerting their effects by changes in gene transcription.
Oestrogen also has a cell surface receptor.

Question 3

Describe 9 effects on the body of high oestrogen.

Answer 3

Weight gain (Na+ and water retention and mildly anabolic)
Raises HDL, lowers LDL
Decreased bone resorption 
Impaired glucose tolerance
Increased blood coaguability
Breast tenderness 
Nausea and vomiting 
Endometrial and breast hyperplasia
Ovarian metaplasia.

Question 4

Describe 7 effects on the body of high progesterone levels.

Answer 4

Produces secretory endometrium
Weight gain (anabolic and fluid retention)
Increases bone mineral density
Mood changes - irritability, PMS, depression, lack of concentration.
Maintains pregnancy
Nausea and vomiting
Acne

Question 5

Describe 6 effects on the body of high testosterone levels.

Answer 5

Male secondary sexual characteristics 
Anabolic
Acne
Voice changes
Increased aggression
Metabolism changes (increased risk of atherosclerotic disease)

Question 6

Describe the pharmacokinetics of oestrogen when given exogenously. (4)

Answer 6

Absorbed in the GI tract, skin or mucous membranes
Metabolised in the liver
Excretion in the urine as glucuronides and sulphates.

Question 7

Describe the pharmacokinetics of progesterone when given exogenously. (5)

Answer 7

Binds to albumin following injection
Stored in adipose tissue
Metabolised in the liver
Excreted via urine conjugated to glucuronic acid.

Question 8

Describe some DDIs with exogenously given sex steroid hormones. (4)

Answer 8

Efficacy of hormone is reduced by CYP450 inducers: carbamazepine, rifampicin, St John’s Wort.
Soya proteins reduce storage of oestrogen so decrease t1/2.

Question 9

Describe the types of HRT, and the consequences of each type. (5)

Answer 9

Opposed oestrogen (oestrogen and progesterone) - increased risk of breast cancer. 
Unopposed oestrogen (only oestrogen) - increased risk of ovarian and endometrial cancer. 
Both increase risk of VTE.

Question 10

Describe the drug Mifepristone. (3)

Answer 10

Progesterone (and glucocorticoid) receptor antagonist, so “anti-progesterone”.
Sensitises the myometrium to prostaglandin induced contraction.
Used for the termination of pregnancy.

Question 11

Define SERM (1)

Answer 11

Selective oestrogen receptor modulator.

Question 12

Describe the drug Clomiphene. (4)

Answer 12

A SERM used in the treatment of anovulation. Competes with oestrogen for the ER receptor, which increases ant pit hormone release to raise oestrogen levels.

Question 13

Describe the drug Raloxifene. (3)

Answer 13

A SERM used to treat osteoporosis and Reduce the risk of breast cancer in post-menopausal women.

Question 14

Describe the drug Tamoxifen. (6)

Answer 14

A SERM given as a pro-drug (activated in the liver). Competes with oestrogen for ER binding.
In breast, acts as an antagonist (causing arrest of the cell cycle); in endometrium, it acts as an agonist.

Question 15

Describe the drug Ulipristal Acetate. (4)

Answer 15

A selective progesterone receptor modulator that acts to delay ovulation. Used as emergency contraception, and in the treatment of uterine fibroids.