5.1 Sex Steroida And Reproductive Health Flashcards
What is the common precursor of sex steroids?
Cholesterol
What are the three major sex steroid hormones?
Oestrogens
Progesterone
Androgens ( testosterone and dihydrotestosterone)
What are the receptor type of steroid receptors?
- Classic nuclear receptor
- also a membrane receptor for oestrogen
How do steroid hormones exert their effects?
Through gene transcription.
Lipophillic steroid ligands enter cell and bind to cell DNA in the nucleolus in influence transcription.
Why are the reactions triggered by intracellular receptors described as slow?
Nuclear receptors, such as those that sex hormones bind to, trigger a change in gene transcription. There is a lag between the binding of ligand to receptor and to the biological effector as gene transcription takes time. Slower as proteins that cause the biological effect have yet to be formed.
What are the major effects of oestrogen?
Stimulates growth of the endometrium and breast; stimulates production of Progesterone Receptor.
What are the major effects of progesterone?
Stimulates growth of the endometrium and breast; maintains pregnancy; inhibits production of oestrogen receptor.
What are the major effects of testosterone?
Stimulates male characteristics; increased body hair; deep voice; anabolism; aggression.
What are the systemic actions of oestrogen?
- Mild anabolic
- Sodium and water retention
- Raises HDL, lowers LDL
- Decrease bone resorption
- Impair glucose tolerance
- Increase blood coagulability
What are the adverse side effects of oestrogen medication?
- Breast tenderness
- Nausea, vomiting
- Water retention
- Increased blood coagulability
- Thromboembolism
- Impaired glucose tolerance
- Endometrial hyperplasia & cancer
- Ovarian metaplasia & cancer
- Breast hyperplasia & cancer (gynecomastia)
What are the systemic actions of progesterone?
Promotes the differentiation and development of secretory epithelium (different from the proliferative epithelium as glands are more coiled as are arterioles) Anabolic Increases bone mineral density Fluid retention Mood changes Maintains pregnancy
What are the adverse side effects of progesterone medication?
Weight gain Fluid retention Anabolic Acne Nausea/vomiting Irritability/depression/PMS Lack of concentration
What are the actions/side effects of testosterone?
Male secondary sex characteristics Anabolic Acne Voice changes Increases aggression Metabolic adverse effects on lipid profiles particularly the HDL-C/LDL-C ratio - increased risk of atherosclerotic disease in males.
What are the stages of development of a follicle cell?
Primordial follicle Primary follicle Secondary follicle Graafian follicle Corpus luteum Corpus albicans
What promotes the development of the primary follicle into the secondary follicle?
FSH released from the anterior pituitary gland in response to activin secreted by the granulosa cells in the early follicular phase
When is progesterone produced in the menstrual cycle?
During the luteal phase by the corpus luteum (after ovulation occurs, lasts 14 days)
What are the 3 layers of the uterus?
Myometrium
Endometrium - basale and functionalis
What are the 3 stages of endometrial development in the menstrual cycle?
Menstrual phase
Proliferation phase
Secretory phase
Describe the pharmokinetics of oestrogen
Absorption: well absorbed in the GI tract, from skin and mucous membranes
Metabolism : in the liver
Excretion : in urine as glucuronides and sulfates
Describe the pharmokinetics of progesterones
Absorption: injected progesterone bound to albumin. poor absorption orally
Distribution : some stored within adipose
Metabolism: Liver
Excretion: in urine conjugated to glucuronic acid
What factors increase the risk of thromboembolism when taking the COCP?
Smoking
Long-term use in women over 35
Obesity
Hypertension
How are oral contraceptives metabolised?
In the liver by CYP 450 enzymes
What might reduce the contraceptive efficacy of oral contraceptives?
Drugs that increase the production of hepatic CYP450 such as:
– anti-epileptics such as carbamazepine or phenytoin
– some antibiotics such as rifampicin and rifabutin
– some natural products such St John’s Wort
Soya protein products that enhance oestrogen absorption, reducing its storage in adipose and muscle and reducing the half life from 15 to 7 hours.
What causes the systemic effects experienced in menopause?
The loss of oestrogen and progesterone previously secreted by follicles during reproductive life.
Why is HRT used?
To replace the oestrogen and progesterone no longer being produced during the menopause. To helps relieve menopausal side effects:
- hot flushes/ sweats/ dyspareunia
- osteoporosis
What steroids are used in HRT?
Oestradiol (1-2mg/day) Premarin Provera Norethisterone Levonorgestrel
What are possible routes of administration of HRT?
Oral Transdermal Implant Transvaginal Nasal
What are the risk factors of HRT?
- Unopposed oestrogen: increased risk of developing endometrial and ovarian cancers.
- Opposed oestrogen: increased risk of breast cancer
- increased risk of venous thromboembolism
- increased risk of stroke (oral)
Why should HRT not be used to reduce heart disease risk?
Although HRT does have a beneficial effect on lipid profile (decreasing cholesterol) the increased risk of venous thromboembolism and stroke means negative effects out way positive effects. More harm than good.
What is the main drug class used to treat osteoporosis?
Bisphosphonates (analogue of pyrophosphates)
Describe the mechanism of action of bisphosphates?
Reduce bone reabsorption/turnover. Act by controlling osteoclasts activity.
What is the uses of bisphosphonates?
- Prophylaxis and treatment of osteoporosis
* Other uses include management of other diseases involving bone e.g. Paget’s disease of bone, malignancy
What are the pharmokinetic considerations of bisphosphonates?
Long biological half life
Poor gut absorption
Absorption affected by food (esp milk) so must be taken on an empty stomach
What are the adverse drug reactions of bisphosphonates?
Upper GI affects - oesophagitis (sit down/stand for 30 mins after taking - dont lie down)
Hypocalcaemia - check calcium and vitamin D levels prior to starting treatment
What is finasteride?
- 5 Alpha reductase inhibitor
- inhibits the enzyme that converts testosterone to dihydrotestosterone
- used to treat BPH
What is RU486 (mifepristone) used for?
Termination of pregnancy
Antiprogesterone
What is the mechanism of action of mifepristone?
Progesterone and glucocorticoid receptor antagonist
Sensitises the myometrium to prostaglandin-induced contractions
What is a SERM?
Selective estrogen receptor modulator ( antagonist/agonist)
Give examples of SERMs
Tamoxifen
Raloxifen
What are the indications for clomiphene
Used in the treatment of anovulation
What is the mechanism of action of clomiphene?
Competes with oestrogen for ER binding. Leads to ovulation induction through increased production of anterior pituitary hormones.
Describe the mechanism of action of tamoxifen
- pro-drug so needs metabolism in the liver to produce active metabolites.
- active metabolites compete with oestrogen binding at the ER
- in endometrium acts as ER agonist
- in breast acts as ER antagonist
What are the indications of tamoxifen?
Breast cancer
Why is there potential for genotype game before prescribing tamoxifen?
Tamoxifen is a prodrug. Some patients have different isoforms of the enzyme that typically breakdown tamoxifen into its active metabolites that are not capable of producing the active derivative. Therefore they will have no benefit from tamoxifen treatment.
What is ulipristal acetate?
A selective progesterone receptor modulator.
What is ulipristal acetate used for?
Emergency contraception to delay or inhibit ovulation
Treatment for uterine fibroids
