Session 3 - Pharmacology of Sex and Steroids

Question 1

Give 6 actions of oestrogens

Answer 1

o	Mild anabolic
o	Sodium and water retention
o	Raise HDL, Lower LDL
o	Decrease Bone Resorption
o	Impair Glucose Tolerance
o	Increase Blood Coagulability

Question 2

Give 7 side-effects Oestrogens

Answer 2

o	Breast tenderness
o	Nausea, vomiting
o	Water retention
o	Increased Coagulability
o	Thromboembolism
o	Impaired glucose tolerance
o	Endometrial hyperplasia & cancer

Question 3

Give 5 actions of progesterone

Answer 3

o	Secretory endometrium
o	Anabolic
o	Increase bone mineral density
o	Fluid retention
o	Mood changes

Question 4

Give 8 side effects of progesterones

Answer 4

o	Weight gain
o	Fluid retention
o	Anabolic
o	Acne
o	Nausea vomiting
o	Irritability
o	Depression
o	Lack of concentration

Question 5

Give three actions of testosterone

Answer 5

o Male secondary sex characteristics
o Anabolic
o Voice changes

Question 6

Give 3 side effects of testosterone

Answer 6

o Acne
o Aggression
o Metabolic adverse effect on lipids

Question 7

How are sex hormones transported?

Answer 7

o Transported bound to Sex Hormone Binding Globulin (SHBG) (except progesterone) and albumin (mainly progesterone).

Question 8

How are sex steroids metabolised?

Answer 8

o Metabolism is via the Liver, Progesterone is almost totally metabolised in one passage through the liver
o Metabolites excreted in the Urine (as glucuronides and sulphates)

Question 9

Outline the mechanism of action of sex steroids

Answer 9

Like all steroid hormones, sex steroids exert their effect via Nuclear Receptors. These receptors are found in the cytoplasm, complexed with heat shock proteins. Following the diffusion (or possibly transport) of their ligand into the cell and high-affinity binding, these receptors form a Homodimer with another ligand-receptor complex and translocate to the nucleus.

In the nucleus, the steroid-receptor complex homodimers can Transactivate or Transrepress genes by binding to Positive or Negative Hormone Response Elements. Large numbers of genes can be regulated in this way by a single ligand.

Steroids may also bind to receptors that are already present inside the nucleus, which will then bind to the HRE.

Question 10

What are the two hormones used in hormonal contraception?

Answer 10

Progesterone

Oestrogen

Question 11

How does progesterone prevent conception?

Answer 11

o Thick, ‘hostile’ cervical mucus plug
 Prevents sperm from entering uterus
 Main contraceptive action of progesterone
o Negative feedback to hypothalamus / pituitary
 Decreases frequency of GnRH pulses
 Inhibits follicular development

Question 12

How does oestrogen prevent conception?

Answer 12

o Oestrogen negatively feeds back on anterior pituitary
o Loss of positive feedback mid-cycle
 No LH surge

Question 13

What does a COCP contain?

Answer 13

Oestrogen and progestogen (a progesterone analogue)

Question 14

How does the CoCP work?

Answer 14

Mimics the luteal phase of hte menstriual cycle and suppresses the release of Gonadotrophins via negative feedback.
Follicular selection and maturation, LH sruge and ovulation does not take place.

Also effects CERVICAL MUCUS and the ENDOMETRIUM

Question 15

What is the route of administration for the COCP?

Answer 15

 Oral

 One a day for 21 days, then break, placebo or iron pill for 7 days

Question 16

Why is the COCP prescribed?

Answer 16

Contraception

Menstrual symptoms

Question 17

What are some contraindications for COCP?

Answer 17

 Pregnancy, breast feeding, history or risk factors of heart disease, hypertension, hyperlipidaemia or any prothrombotic coagulation abnormality, diabetes mellitus, migraine, breast or genital tract carcinoma, liver disease

Question 18

Give some adverse effects of the COCP?

Answer 18

 VENOUS THROMBOEMBOLISM, HYPERTENSION, decreased glucose tolerance, headaches, mood swings, acne, flushing, nausea, vomiting, headache, amenorrhoea of variable duration on pill cessation

Question 19

What is the effect of the progesterone only pill?

Answer 19

This causes thickening of cervical mucus, preventing sperm penetration. It also has an adverse effect on the endometrium, affecting implantation. Contraception is less reliable than the COCP. It also causes suppression of gonadotrophin secretion, and occasionally ovulation, but the latter effect does not occur in the majority of women

Question 20

What is the route of administration of the POP?

Answer 20

 Oral
 Daily, at the same time, starting at day 1 of menstrual cycle. If delay in taking the pill is greater than 3 hours, contraceptive effect may be lost

Question 21

What are the indications of the POP?

Answer 21

 Contraception – More suitable for heavy smokers and patients with hypertension or heart disease, diabetes mellitus, or other contraindications for oestrogen therapy (see above COCP)

Question 22

What are the contradindications of the POP?

Answer 22

 Pregnancy, arterial disease, liver disease or breast or genital tract carcinoma

Question 23

What are the adverse effects of the POP?

Answer 23

 Menstrual irregularities, nausea, vomiting and headache, weight fain, breast tenderness

Question 24

What are the main side effects of the COCP?

Answer 24

o Venous Thromboembolism (rare)
o Hypertension
o Amenorrhoea of variable duration on pill cessation
o Flushing, headaches, nausea, acne, mood swings, weight gain (common)

Question 25

What are the main drug interactions of the COCP? (2)

Answer 25

o Metabolism is by CYP450  Therefore effected by inducers/inhibitors  Enzyme inducers can lower levels of COCP causing contraception failure o Broad spectrum antibiotics (e.g. Amoxicillin)  Enterohepatic recirculation of oestrogen increases the efficacy of the COCP. If gut flora is killed by a broad spectrum antibiotic this is reduced and may cause contraception failure

Question 26

What are some adverse effects of POP?

Answer 26

o Menstrual irregularities o Nausea, vomiting and headache o Weight gain o Breast tenderness

Question 27

What are some drug interactions of POP?

Answer 27

o Metabolism is by CYP450  Therefore effected by inducers/inhibitors  Enzyme inducers can lower levels of POP causing contraception failure

Question 28

What is the most common route of sex steroid admin?

Answer 28

Oral

Question 29

What are the advantage of transdermal sex steroid? (3)

Answer 29

o May reduce risk in turns of DVT, Thromboembolism by bypassing the Liver and giving smaller doses o Important for people who complain of GI side Effects o Slow, gradual release of steroid (Progestin)

Question 30

What is the advantage of impants?

Answer 30

Slow, gradual release of steroid (Progestin)

Question 31

Give five methods of sex steroid admin?

Answer 31

``` Oral Transdermal Implants Nasal Vaginal ```

Question 32

Give a long term method of contraception?

Answer 32

Depot progesterone | Intramuscular implant of progesterone giving long term contraception - same mechanism as POP

Question 33

What is the morning after pill?

Answer 33

o ‘Morning after pill’ – Up to 72hrs after sex  Very high oral doses of progesterone (1.5mg) alone, or a Progestogen with an oestrogen to prevent implantation of fertilised egg

Question 34

What level of effectiveness is morning after pill?

Answer 34

 75% effective

Question 35

What is indication for morning after pill?

Answer 35

– Emergency Contraception after unprotected sex

Question 36

Contraindication for Morning after pill?

Answer 36

Oestrogen contraindications (see above), need to ask about cycle and when they had sex to determine if the woman is already pregnant.

Question 37

What contraception can be used up to 120 hours after sex?

Answer 37

 Progesterone receptor modulator |  Copper IUD

Question 38

How can you manage uterine bleeding?

Answer 38

The COCP can be used to manage abnormal uterine bleeding. Basically ‘tricks’ the body into thinking it is in the post ovulatory, luteal phase so offers a good method of cycle control.

Question 39

What can be used to cure menopausal symptoms?

Answer 39

Hormone Replacement Therapy (HRT)

Question 40

What are five risks of HRT?

Answer 40

```  Unopposed oestrogen – Inc. endometrial and ovarian cancers  Increase breast cancer risk  Increased IHD and stroke risk  Increased risk of thromboembolism  Uterine bleeding ```

Question 41

Give two adverse effects of HRT?

Answer 41

 Adverse effect on lipid profile |  Adverse effect on thrombophilia profile