Session 3 - Pharmacology of Sex and Steroids Flashcards
Give 6 actions of oestrogens
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
Give 7 side-effects Oestrogens
o Breast tenderness o Nausea, vomiting o Water retention o Increased Coagulability o Thromboembolism o Impaired glucose tolerance o Endometrial hyperplasia & cancer
Give 5 actions of progesterone
o Secretory endometrium o Anabolic o Increase bone mineral density o Fluid retention o Mood changes
Give 8 side effects of progesterones
o Weight gain o Fluid retention o Anabolic o Acne o Nausea vomiting o Irritability o Depression o Lack of concentration
Give three actions of testosterone
o Male secondary sex characteristics
o Anabolic
o Voice changes
Give 3 side effects of testosterone
o Acne
o Aggression
o Metabolic adverse effect on lipids
How are sex hormones transported?
o Transported bound to Sex Hormone Binding Globulin (SHBG) (except progesterone) and albumin (mainly progesterone).
How are sex steroids metabolised?
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)
Outline the mechanism of action of sex steroids
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.
What are the two hormones used in hormonal contraception?
Progesterone
Oestrogen
How does progesterone prevent conception?
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
How does oestrogen prevent conception?
o Oestrogen negatively feeds back on anterior pituitary
o Loss of positive feedback mid-cycle
No LH surge
What does a COCP contain?
Oestrogen and progestogen (a progesterone analogue)
How does the CoCP work?
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
What is the route of administration for the COCP?
Oral
One a day for 21 days, then break, placebo or iron pill for 7 days
Why is the COCP prescribed?
Contraception
Menstrual symptoms
What are some contraindications for COCP?
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
Give some adverse effects of the COCP?
VENOUS THROMBOEMBOLISM, HYPERTENSION, decreased glucose tolerance, headaches, mood swings, acne, flushing, nausea, vomiting, headache, amenorrhoea of variable duration on pill cessation
What is the effect of the progesterone only pill?
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
What is the route of administration of the POP?
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
What are the indications of the POP?
Contraception – More suitable for heavy smokers and patients with hypertension or heart disease, diabetes mellitus, or other contraindications for oestrogen therapy (see above COCP)
What are the contradindications of the POP?
Pregnancy, arterial disease, liver disease or breast or genital tract carcinoma
What are the adverse effects of the POP?
Menstrual irregularities, nausea, vomiting and headache, weight fain, breast tenderness
What are the main side effects of the COCP?
o Venous Thromboembolism (rare)
o Hypertension
o Amenorrhoea of variable duration on pill cessation
o Flushing, headaches, nausea, acne, mood swings, weight gain (common)
What are the main drug interactions of the COCP? (2)
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
What are some adverse effects of POP?
o Menstrual irregularities
o Nausea, vomiting and headache
o Weight gain
o Breast tenderness
What are some drug interactions of POP?
o Metabolism is by CYP450
Therefore effected by inducers/inhibitors
Enzyme inducers can lower levels of POP causing contraception failure
What is the most common route of sex steroid admin?
Oral
What are the advantage of transdermal sex steroid? (3)
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)
What is the advantage of impants?
Slow, gradual release of steroid (Progestin)
Give five methods of sex steroid admin?
Oral Transdermal Implants Nasal Vaginal
Give a long term method of contraception?
Depot progesterone
Intramuscular implant of progesterone giving long term contraception - same mechanism as POP
What is the morning after pill?
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
What level of effectiveness is morning after pill?
75% effective
What is indication for morning after pill?
– Emergency Contraception after unprotected sex
Contraindication for Morning after pill?
Oestrogen contraindications (see above), need to ask about cycle and when they had sex to determine if the woman is already pregnant.
What contraception can be used up to 120 hours after sex?
Progesterone receptor modulator
Copper IUD
How can you manage uterine bleeding?
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.
What can be used to cure menopausal symptoms?
Hormone Replacement Therapy (HRT)
What are five risks of HRT?
Unopposed oestrogen – Inc. endometrial and ovarian cancers Increase breast cancer risk Increased IHD and stroke risk Increased risk of thromboembolism Uterine bleeding
Give two adverse effects of HRT?
Adverse effect on lipid profile
Adverse effect on thrombophilia profile
