Repoductive And Post-Reporductive Health Flashcards
What drug group are important in reproductive and post-reproductive health?
Sex steroid hormones (oestrogen, progestogens, androgens)
Inhibitors and antagonists (RU486, finasteride)
MIxed agonists / antagonists (SERMs and SPRMs)
What are the sex hormones and what are they synthase from?
From cholestrol to
Progesterone to
Testosterone to
Oestrogen (estradiol)
How do steroid hormones act classically?
Classically, they act through nuclear receptors.
They exert effect through gene transcription
But also a membrane receptor for oestrogen
What are the major effects of oestrodiol?
Stimulates growth of the endometrium and breast; stimulates production off PR
What are the major effects of progesterone?
Stimulates growth of the endometrium and breast; maintains pregnancy; inhibits production of ER
What are the major effects of testosterone?
Stimulates male characteristics; hairy body; deep voice; anabolism; aggression
What are the actions of oestrogen?
Mild anabolic Na and water retention Raised HDL, lower LDL Decreases bone respiration Impair glucose tolerance Increase blood oagulabulity
What are the side effects of oestrogen?
Breast tenderness Nausea, vomitting Water Retention Increased blood coagulability Thromboembolism Impaired glucose tolerance Endometrial hyperplasia and cancer Ovarian metaplasia and cancer Breast hyperplasia and cancer
What are the actions of progesterone / progestin?
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 and side effects of testosterone?
Male secondary sexual characteristics Anabolic Acne Voice changes Increases aggression
Metabolic - adverse effects on lipid profiles particularly the HDL-C/ LDL-C ratio hence increased risk of atherosclerotic disease in males
Outline the menstrual cycle
Ovulation occurs due to LH surge
Oestrogen and progesterone have different effects on endometrial tissue and on cervical mucus.
Oestrogen and progesterone together produces suppression of HPO axis.
Summarise hormonal contraception
Interruption of physiological control of the menstrual cycle Endometrial and cervical mucus effects Inhibition do ovulation Many routes of administration: -Oral -Nasal -Transdermal -Implants
Describe the pharmacokinetic points regarding oestrogen
Natural and synthetic oestrogen are well absorbed in the GI tract
Also readily absorbed from skin and mucus membranes
Metabolism - liver
Excretion - in the urine as glucuronides and sulphates
Describe the pharmacokinetics of progesterone
Injected progesterone is bound to albumin with one stored on adipose
Metabolised in liver
Metabolites excreted in the urine conjugated to glucuronic acid.
What are the adverse effects of COP?
Risk of thromboembolism is small (15/100,000)
Smoking increases the risk substantially
Also for long term use in women over 35
Also consider obeisity and hypertension
Describe the pharmacokinetic points of the oral contraceptive pill
COCP and POP contraceptives are metabolised in the liver by CYP 450 enzymes
Therefore efficacy is reduced by enzyme inducing drugs:
Anti-epileptics, some antibiotics, some natural products e.g. St Johns Wart.
Soya products enhance oestrogen absorption and reduce its storage in adipose and muscle and so cause the half life to be reduced form 15 to 7 hours.
Summarise the menopause
Ovarian follicle supple 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
Why prescribe HRT?
Symptoms: e.g. hot flushes / sweats and dyspareunia
Osteoporosis
NOT for heart disease
What are the routes do administration of HRT?
Oral Transdermal Implant Transnational Nasal
What are the risks of HRT?
Unopposed oestrogen - rsk of developing endometrial and ovarian cancers
Opposed oestrogen - Increase risk of developing cancer
Increase risk of venous thromboembolism
Cardiovascular disease
Increased risk of stroke (oral not transdermal)
What is mifepristone (RU486)?
Progesterone receptor antagonists
Act as anti-progesterone
Sensitising the myometium to prostaglandin-induced constructions.
Used for termination of pregnancy
What is a SERM?
Selective oestrogen receptor modulator.
cf pure agonist and pure antagonist.
SERMs are distinct in having varying effects in differing tissues.
E.g. Tamoxifen, Raloxifene
What is clomiphene?
Clomiphene used in the treatment of anovulation
Completes with oestrogen for ER bidding
Leads to ovulation induction though increased production of anterior pituitary hormones
What is tamoxifen?
A pro-drug - little affinity for the ER.
Metabolised in the liver to a active derivative
Tamoxifen active metabolites conpete with oestrogen for binding to the ER
How does Tamoxifen work?
A pro-drug -little affinity for the ER. Metabolised in the liver to an active derivatives. Tamoxifen active metabolites compete with oestrogen binding to the ER.
Acts as a SERM
Has converse effects in breast tissue and endometrial tissue
In Endometrium, acits as ER agonist
In breast, acts as ER antagonist
In breast, binding of the ER following tamoxifen treatment causes cells to arrest the cell cycle
What is Ulipristal acetate?
Selective progesterone modulator
When used for emergency contraception of the primary mode of action os through to be most likely the delay or inhibition of ovulation
Also effective for the treatment of uterine fibroids
