Sex Steroids

Question 1

How are sex steroids transported around the body?

Answer 1

Bound to SHBG (not progesterone) and albumin

Question 2

What happens when a steroid binds to its receptor?

Answer 2

The steroid binds at the ligand binding site and causes removal of the heat shock protein to reveal the DNA binding site to regulate DNA synthesis in the nucleus

Question 3

What effect does oestrogen have on progesterone receptors?

Answer 3

Stimulates production

Question 4

What effect does progesterone have on oestrogen receptors?

Answer 4

Inhibits production

Question 5

How are metabolites of sex steroids excreted?

Answer 5

In urine as glucuronides and sulphates

Question 6

What are the main actions of oestrogen?

Answer 6

Mildly anabolic

Na+ and K+ retention

Raises HDLs and lowers LDLs

Reduces glucose tolerance

Increases coagulability

Decreases bone resorption

Question 7

What are the ADRs of oestrogen?

Answer 7

Breast tenderness

Nausea, vomiting

Water retention

Increased coagulability

Endometrial hyperplasia and cancer

Ovarian metaplasia and cancer

Breast hyperplasia and cancer

Question 8

What are the actions of progesterone?

Answer 8

Stimulates a secretory endometrium

Anabolic

Increased bone mineral density

Fluid retention

Mood changes

Maintains pregnancy

Question 9

What are the ADRs of progesterone?

Answer 9

Weight gain

Fluid retention

Acne

Nausea, vomiting

Irritability

Depression

Lack of concentration

Question 10

What are the actions/ADRs of testosterone?

Answer 10

Make secondary sexual characteristics

Anabolic

Acne

Voice changes

Increases aggression

Affects HDL:LDL increasing the risk of atherosclerosis

Question 11

What is the difference between monophasic, biphasic and triphasic COCPs?

Answer 11

Monophasic - each tablet contains the same

Biphasic - fixed oestrogen, progestin increases in the second half

Triphasic - fixed/variable oestrogen, progestin increases in 3 phases

Question 12

What are the contraindications for prescribing COCP?

Answer 12

Hypertension, high BMI, VTE history, prolonged immobility, breast cancer, smoking over 35

Question 13

Describe the mechanism of action of COCP

Answer 13

Oestrogen and progesterone feed back negatively on the hypothalamus/anterior pituitary preventing follicle growth and the LH surge (thus ovulation). Progesterone causes thickening of the cervical mucus and thins the lining of the endometrium.

Question 14

What are the ADRs of COCP?

Answer 14

VTE, hypertension, headache, mood swings, increased risk of stroke

Question 15

What are the indications for POP?

Answer 15

Women unsuitable for COCP e.g. Hypertension

Emergency contraception

Question 16

What are the ADRs of the POP?

Answer 16

Irregular menstruation, headaches, breast tenderness, skin tenderness, breast cancer

Question 17

What are the indications for HRT?

Answer 17

Hot flushes/sweats, vaginal dryness/dyspareunia, osteoporosis

Question 18

What should you not prescribe HRT for?

Answer 18

IHD

Question 19

What are the ADRs for ERT and HRT?

Answer 19

ERT (unopposed oestrogen) - increased risk of endometrial and ovarian cancer

HRT (opposed oestrogen) - increased risk of breast cancer

Increased risk of stroke (but beneficial for IHD)

VTE - protein C resistance, increased thrombin

Question 20

What are the two selective estrogen receptor modulators, what are they used for?

Answer 20

They are oestrogen receptor agonists and antagonists in different tissues.

Raloxifene - to prevent breast cancer in postmenopausal women with increased risk of breast cancer/osteoporosis

Tamoxifen - to prevent breast cancer and in the treatment of estrogen receptor positive breast cancer

Question 21

What are the differences in action between raloxifene and tamoxifen?

Answer 21

Raloxifene - antioestrogenic actions at breast and endometrium, oestrogenic effects on bones, lipids and coagulation

Tamoxifen - OESTROGENIC EFFECT AT ENDOMETRIUM (risk of endometrial cancer), lipids and bone, antioestrogenic effects at breast

Question 22

Name an antioestrogen, it’s effect and what it is used for

Answer 22

Clomiphene inhibits oestrogen binding in the anterior pituitary (competes with oestrogen) increasing gonadotrophin release and thus oestrogen, stimulating the ovaries and inducing ovulation.

Used to treat infertility caused by lack of ovulation.

Question 23

Name an antiprogestogen, it’s action and what it is used for

Answer 23

Mifepristone is a PR antagonist in the presence of progesterone and sensitises the uterus to prostaglandin (involved in ischaemic necrosis of the endometrium).

This is used in combination with prostaglandin for medical termination of pregnancy.

Question 24

Name a steroidal anti androgen, how it works and what it is used for.

Answer 24

Cyproterone has week progesterone effects and competes with dihydrotestosterone in androgen tissues. It acts at the hypothalamus to decrease the amount of gonadotrophin.

Used to treat prostatic cancer, precocious puberty in males and masculinisation in women.

Question 25

Name a non steroidal anti androgen, how it works and it’s uses.

Answer 25

Flutamide competes with androgens for ARs in the prostrate, preventing hyperplasia.

Used to treat prostate cancer

Question 26

Name an anti androgen enzyme inhibitor, how it works and when it is used

Answer 26

Finasteride inhibits 5a reductase which converts testosterone to dihydrotestosterone which has higher affinity for AR in the prostate.

Used to treat benign prostatic hyperplasia