4.1 Sex Hormone Drugs

Question 1

How do Sex Steroids Travel in the blood?

Answer 1

The travel bound to Albumin and Sex Hormone Binding Globulin (oestrogen increases this production)
Therefore have a long half life

Except progesterone which travels as a free drug (1st pass effect!)

Question 2

What is the structure of SHs?

Answer 2

They all have a common ring structure
Derived from Cholesterol
2 Pathways to produce (one gives testosterone, the other O and P)
They are lipophilic and get stored in tissues

Question 3

How does oestrogen get metabolised?

Answer 3

It is absorbed in the gut
Travels to the liver
Gets conjugated with glucoronide
Then in bile into the small intestine where it isn’t reabsorbed
It is then unconjugated by gut bacteria and reabsorbed in the blood
It can then affect peripheral tissues

Requires CYP450 enzymes

Question 4

Pathway of Action for Oestrodiol

Answer 4

Lipophilic so passes through the cell membrane to intracellular receptors
Goes to the nucleus with receptor
2 Receptors (alpha and beta forms) with similiar structures

Question 5

What factors change the actions of SHs?

Answer 5

The tissue
The receptors present (number and type)
Co-activators/repressers present
The gene targets

Question 6

How does receptor density change throughout the menstrual cycle?

Answer 6

P receptors are high until the mid secretory stage of the cycle
O receptor beta is high at the start of the mid secretory stage and alpha is high after the early secretory stage

Density is high in the female repro tract

Question 7

What does Oestrogen do?

Answer 7

Proliferation of Endometrium and Breast Tissue (tenderness!)
Retain Na/H20
Increases HDLs, Lowers LDLs
Anabolic (increases weight gain, glucose insensitivity)
Increases coagulation
Decreases bone resorption
Increases number of PRs

Question 8

What does progesterone do?

Answer 8

Create secretory endometrium ready for implantation
Maintains pregnancy
Decreases number of ERs 
Mood Changes
Acne
Anabolic, Fluid Retention, Bone Density

Question 9

What does testosterone do?

Answer 9

Male Characteristics
Aggression
Acne
Voice Changes
Increases the LDL/HDL ratio (more risk of atherosclerosis)

Question 10

How do we utilise sex hormones?

Answer 10

Contraceptive Use (pill, implant)
HRT
Androgen Replacement - BPH, Hair Loss
Oestrogen Receptor Blockers (using mild oestrogens) - cancer
Anti-progestins

Question 11

How does the COCP work?

Answer 11

Oestrogen and Progesterone together prevent ovulation (no O only rise -> LH surge)
Oestrogen - non-secretory endothelium
Progesterone - thicker cervical mucus, decreases motility

Question 12

Types of COCP?

Answer 12

Oral, Nasal, Vaginal
Implant,Transdermal

Monophasic, Biphasic, Triphasic
(If levels of P change)

Question 13

What are the adverse effects of the COCP?

Answer 13

Increase risk of DVT - PE - Stroke (Thrombus) Headaches
Weight Gain
Acne
Increase risk of gallstones
Mood Changes
Decreases glucose tolerance

Question 14

What are the DDIs with the COCP?

Answer 14

CYP inducers/inhibitors
Soy (increases absorption)
Broad spectrum antibiotics (affects one oestrogen more than others)

Question 15

How does the Progesterone Only Pill work?

Types

Answer 15

It prevents implantation, ovulation, and thickens the mucus
Use when cannot use COCP

IUCD
Implant
Oral - emergency contraception

Question 16

What are the types of HRT?

Routes?

Answer 16

Oestrogen only preparations (use only if had a hysterectomy)
Combined

Oral, Nasal
Transvaginal/dermal
Implant

Question 17

When do you prescribe HRT?

Answer 17

When symptoms of the menopause are significant

When there is a risk of osteoporosis

Question 18

What are the benefits or HRT?

Answer 18

Prevent Osteoporosis
Reduce symptoms
Increases HDLs

Question 19

What are the risks of HRT?

Answer 19

Can increase risk of breast (and endometrial) cancer

Question 20

What are some Oestrogen receptor antagonists?

Answer 20

Tamoxifen - used in breast cancer, blocks the receptor, decreases proliferation of breast tissue. However it can agonise the receptor of the endometrium

Clomiphene - induce ovulation, inhibit oestrogen in anterior pituitary

Question 21

What are anti-progestins used for?

Answer 21

Induction of labour
Abortion
Rarely used!
They sensitise the uterus to prostaglandins

Question 22

What are antiandrogens used for?

Answer 22

In Dianette, a COCP

Partial agonist to PR

Question 23

What are SERMs?

Uses?

Answer 23

Selective Oestrogen Receptor Modulators
Protect against osteoporosis
Can increase hot flushes
Lowers breast/endometrium proliferation

Question 24

What are androgen replacements?

Answer 24

Used in male pattern baldness
Prevent BPH
Implants, IM, Oral