Flashcards in 4.1 Sex Hormone Drugs Deck (24)
How do Sex Steroids Travel in the blood?
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!)
What is the structure of SHs?
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
How does oestrogen get metabolised?
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
Pathway of Action for Oestrodiol
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
What factors change the actions of SHs?
The receptors present (number and type)
The gene targets
How does receptor density change throughout the menstrual cycle?
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
What does Oestrogen do?
Proliferation of Endometrium and Breast Tissue (tenderness!)
Increases HDLs, Lowers LDLs
Anabolic (increases weight gain, glucose insensitivity)
Decreases bone resorption
Increases number of PRs
What does progesterone do?
Create secretory endometrium ready for implantation
Decreases number of ERs
Anabolic, Fluid Retention, Bone Density
What does testosterone do?
Increases the LDL/HDL ratio (more risk of atherosclerosis)
How do we utilise sex hormones?
Contraceptive Use (pill, implant)
Androgen Replacement - BPH, Hair Loss
Oestrogen Receptor Blockers (using mild oestrogens) - cancer
How does the COCP work?
Oestrogen and Progesterone together prevent ovulation (no O only rise -> LH surge)
Oestrogen - non-secretory endothelium
Progesterone - thicker cervical mucus, decreases motility
Types of COCP?
Oral, Nasal, Vaginal
Monophasic, Biphasic, Triphasic
(If levels of P change)
What are the adverse effects of the COCP?
Increase risk of DVT - PE - Stroke (Thrombus) Headaches
Increase risk of gallstones
Decreases glucose tolerance
What are the DDIs with the COCP?
Soy (increases absorption)
Broad spectrum antibiotics (affects one oestrogen more than others)
How does the Progesterone Only Pill work?
It prevents implantation, ovulation, and thickens the mucus
Use when cannot use COCP
Oral - emergency contraception
What are the types of HRT?
Oestrogen only preparations (use only if had a hysterectomy)
When do you prescribe HRT?
When symptoms of the menopause are significant
When there is a risk of osteoporosis
What are the benefits or HRT?
What are the risks of HRT?
Can increase risk of breast (and endometrial) cancer
What are some Oestrogen receptor antagonists?
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
What are anti-progestins used for?
Induction of labour
They sensitise the uterus to prostaglandins
What are antiandrogens used for?
In Dianette, a COCP
Partial agonist to PR
What are SERMs?
Selective Oestrogen Receptor Modulators
Protect against osteoporosis
Can increase hot flushes
Lowers breast/endometrium proliferation