Gonadal Steroids Flashcards
What are the sex steroids derived from?
Cholesterol
What are the actions of oestrogens in general?
Anabolic Sodium and water retention Raised HDL, lowered LDL Deceased bone resorption Impaired glucose tolerance Increased blood coagulability
Adverse effects of oestrogens?
Breast tenderness Nausea and vomiting Water retention Increased coagulability - thromboembolism Impaired glucose tolerance Endometrial hyperplasia and cancer
Actions of progesterone?
Secretory endometrium Anabolic Increased bone mineral density Fluid retention Mood changes
Adverse effects of progesterone?
Weight gain Fluid retention Anabolic Acne Nausea and vomiting Irritability Depression and PMS Lack of concentration
Actions and side effects of testosterone?
Make secondary sexual characteristics Anabolic Acne Voice changes Aggression Metabolic adverse effects on lipids
What are the uses of testosterone?
Hormone replacement therapy in men due to decreasing testosterone production with age
Testosterone deficiency - congenital or acquired
Causes of testosterone deficiency?
Testicular dysfunction
Hypothalamic-pituitary dysfunction (secondary hypogonadism)
How can testosterone be administered?
Implants
IM (enenthate, propionate)
Orally (undecanoate, mesterolone)
How are sex steroids transported?
Bound to SHBG (except progesterone)
Albumin
What is the metabolism of progesterone?
Almost totally metabolised in one passage through the liver
Metabolites excreted in urine as glucuronides and sulphates
What are the types of COCP?
Monophasic - constant dose of oestrogen and progesterone for 21 days
Triphasic - doses altered throughout the cycle
Everyday pill - 7 days are a placebo
How does the COCP work?
Suppresses ovulation by inhibiting FSH and LH
Adverse effect on cervical mucus and endometrium
Which drugs can reduce the efficacy of the COCP?
Enzyme-inducing drugs such as
- carbamazepine
- rifampicin
- St John’s Wort
- phenytoin
Broad spectrum antibiotics - due to effects on intestinal flora
How do broad spectrum antibiotics reduce the efficacy of the COCP?
Affect the intestinal flora which play a role in enterohepatic recycling
As they decrease, so does the amount of drug re-entering the systemic circulation
Adverse effects of the COCP?
Venous thromboembolism MI Hypertension Decreased glucose tolerance Increased risk of stroke in women with focal migraine Headaches Mood swings Cholestatic jaundice Gall stones Precipitate polyphyria
What are the different types of progesterones?
Levonorgestrel Norethisterone Etynodiol Diacetate Desogestrel
What type of progesterone is given in the injection?
Medroxy progesterone
What type of progesterone is given in the implant?
Etonogestrel
How does progesterone act as a contraception?
Negative effect on cervical mucus and endometrium
Problem with progesterone contraception?
Poor control of menstrual cycle because ovulation can still occur
What are the two types of emergency contraception and when can they be taken?
Levonorgestrel (levonelle) - up to 72 hours Ullipristal acetate (ellaOne) - up to 120 hours
How does levonorgestrel prevent pregnancy?
Inhibits ovulation
How does ullipristal acetate prevent pregnancy?
Progesterone receptor modulator
How does the copper IUD prevent pregnancy?
Toxic to sperm
How do oestrogen and progesterone affect the amount of GnRH secreted?
Oestrogen reduces the amount secreted per pulse
Progesterone reduces the frequency of pulses
Why is HRT given?
Relieve menopausal-related symptoms such as hot flushes
Can reduce osteoporosis
Reduced risk of heart disease
Which hormones are given in HRT and why?
Oestrogen - this is the one that needs to be replaced
Progesterone - to protect against risk of endometrial carcinoma
What is a disadvantage of sequential combined HRT?
Causes periods every month
Risks of HRT?
Endometrial and ovarian cancer with unopposed oestrogen Breast cancer IHD and stroke Venous thromboembolism Uterine bleeding Adverse effect on lipid profile Adverse effect on thrombophilia profile
Modes of administration of HRT?
Oral Transdermal Implant Transvaginal Nasal
What are anti-oestrogens?
Weak oestrogens that block receptors
Why is clomiphene (an anti-oestrogen) given?
Stops oestrogen from binding to the anterior pituitary, inhibiting negative feedback, resulting in increased GnRH, FSH and LH release - treats anovulation
Why is tamoxifen given?
Oestrogen receptor antagonist to treat breast cancer
Induces ovulation
What are anti-progesterones (mifepristone) used for?
Medical termination of pregnancy
Induce labour
How does mifepristone work?
It is a partial agonist of progesterone receptors so inhibits progesterone action
Sensitises the uterus to prostaglandins
What are anti-androgens (eg cyproterone) used for?
It is a progesterone derivative - used in COCP
Has a weak progesterones effect by being a partial against to progesterone receptors and competes with dihydrotestosterone
Prostate cancer
Hirsutism
Acne
What are selective oestrogen receptor modulators used for (eg Raloxifene)
Reduce risk of invasive breast cancer in post-menopausal women with osteoporosis
No proliferative effects on endometrium or breast
Protects against osteoporosis
Downside of Raloxifene?
Can increase hot flushes
