8. Sex steroids Flashcards
(47 cards)
What are sex steroid hormones synthesised from?
Cholesterol
What receptors do steroid hormones have?
- Classic nuclear receptors
- Exert effects through gene transcription
- But also a membrane receptor for oestrogen
what are the 3 main sex steroid hormones?
Oestrogens, progestagens, androgens
What are the major effects of oestradiol?
Stimulates growth of the endometrium and breast; stimulates production of Progesterone receptor (PR).
What are the major effects of progesterone?
Stimulates growth of the endometrium and breast; maintains pregnancy; inhibits production of ER(oestrogen receptor).
What are the major effects of testosterone?
Stimulates male characteristics; hairy body; deep voice; anabolism; aggression.
What are the actions of oestrogen?
- Mild anabolic
- Sodium and water retention
- Raises HDL, lowers LDL
- Decrease bone resorption (oestrogen decreases osteoclast function)
- Impair glucose tolerance
- Increase blood coagulability
What are the side effects of oestrogen?
- Breast tenderness
- Nausea, vomiting
- Waterretention
- Increased blood coagulability
- Thromboembolism
- Impaired glucose tolerance
- Endometrial hyperplasia & cancer
- Ovarian metaplasia & cancer
- Breast hyperplasia & cancer
What are the actions of progesterone?
- Secretory endometrium
- Anabolic
- Increases bone mineral density
- Fluid retention
- Mood changes
- Maintains pregnancy
What are the side effects of progesterone?
- Weight gain
- Fluid retention
- Anabolic
- Acne
- Nausea/vomiting
- Irritability Depression, PMS
- Lack of concentration
What are the actions of testosterone?
- Male secondary sex characteristics
- Anabolic
- Voice changes
What are the side effects of testosterone?
Metabolic - adverse effects on lipid profiles particularly the HDLC/LDL-C ratio hence increased risk of atherosclerotic disease in males
• Acne
• Increases aggression
describe the role of oestrogen and progesterone in the menstrual cycle
- Ovulation occurs due to the LH surge
- Oestrogen and progesterone have differing effects on endometrial tissue and on cervical mucus
- oestrogen promotes thin watery mucus for stern transport and progesterone promotes thick cervical mucus to block any further sperm from entering
- Oestrogen and progesterone together produces suppression of the HPO axis
What are the pharmacokinetics of oestrogen?
- Natural and synthetic oestrogens well absorbed in the GI tract
- Also readily absorbed from skin and mucous membranes
- Metabolism - liver
- Excretion - in the urine as glucuronides and sulfates
What are the pharmacokinetics of progesterone?
- Injected progesterone is bound to albumin with some stored in adipose tissue
- Metabolised in the liver
- Metabolites excreted in the urine conjugated to glucuronic acid
WHat are COCP and POP metabolised by?
CYP enzymes
what are Adverse effects of the combined pill?
• small Risk of thromboembolism
what increases the risk of thromboembolism with COCP?
- Smoking increases this risk substantially
- Also for long-term use in women over 35
- Also consider other risk factors such as obesity and hypertension
Give examples of drugs that reduce efficacy of oral contraceptives and how?
- anti-epileptics such as carbamazepine or phenytoin;
- some antibiotics such as rifampicin and rifabutin and
- some natural products such St John’s Wort
All increase production of hepatic CYP450 so speed up metabolism of drug
What increases absorption of oestrogen?
Soya protiens - also reduce oestrogen storage in adipose tissue and decrease its half life
What is HRT prescribed for?
- symptoms of menopause: e.g. hotflushes /sweats and vaginal dryness / dyspareunia
- osteoporosis - both oestrogen and progesterone limit bone resorption
(should not be given for heart disease)
what is menopause and what causes symptoms?
• Ovarian follicle supply depleted
• Consequently ovarian sex steroid production stops
• End of female reproductive capacity
• ALSO
Loss of oestrogen and progesterone leads to a range of systemic effects as symptoms of menopause
which steroids are used for HRT?
• Oestradiol: e.g. valerate, enanthate, micronised oestradiol, ethinyl estradiol, etc.
(1-2 mg/day)
• Premarin® (0.625-1.25 mg/day)
• Medroxyprogesterone acetate (Provera®) (2.5 mg/day) • Norethisterone (1 mg/day)
• Levonorgestrel (1.5 mg/day)
what are the routes of administration of HRT?
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