Oral Contraceptives, Menopause and HRT Flashcards
What is menopause?
Permanent cessation of menstruation
Loss of ovarian follicular activity
Usually occurs 45-55 yrs
What is the term given to the period of transition just before menopause? Describe this period of transition.
Climacteric period
Periods irregular until they completely stop
State 6 symptoms of menopause.
Hot flushes Urogenital Atrophy (leads to dyspareunia – painful sex) Sleep disturbance Decreased libido Depression Joint pain
What do the ovaries produce that feeds back on the HPG axis?
Oestradiol + Inhibin B
How does feedback on the HPG axis change in menopause?
There is a loss of ovarian follicular activity, so production of oestradiol+ inhibin is reduced
Results in less negative feedback on the HPG axis
LH + FSH rise
What would you expect the LH and FSH levels of a menopausal woman to be?
High – because of the loss of oestrogen + inhibin production
What are the main complications of menopause?
Osteoporosis (protective effect of oestrogen on bone is lost, loss of bone matrix, 10-fold increased risk of fracture) Cardiovascular disease (women are protected against CVD before menopause)
What are the risks of giving oestrogen as part of HRT?
Endometrial hyperplasia, which increases the risk of endometrial carcinoma
How is the risk of endometrial cancer when taking oestrogen prevented?
Combine with progesterone
Progesterone prevents endometrial hyperplasia
In which subset of patients would you give oestrogen only HRT?
Patients who have had a hysterectomy
There is no uterus so no endometrium to stimulate with oestrogen
Describe the 2 different formulations of HRT.
Cyclical: take oestradiol every day + progesterone for the last 12-14 days
Combined continuous: take a little oestrogen + progesterone every day
State 4 different types of oestrogen preparations.
Oral oestradiol (1 mg)
Oral conjugated equine oestradiol (0.625 mg)
Transdermal oestradiol (50 mcg/day)
Intravaginal
Describe the absorption and metabolism of oestradiol.
Oestradiol is absorbed well but it is heavily metabolised in the liver (1st pass) so bioavailability is very low.
Thus, in oral preparations, a high dose of oestradiol is required
Name a semi-synthetic oestrogen that’s used in oral contraceptives.
Ethinyl oestradiol
Ethinyl group protects the drug from hepatic 1st pass metabolism.
What is the difference between the types and dose of oestrogen given in HRT compared to the oral contraceptive?
HRT: giving a little bit of oestrogen to prevent symptoms of menopause.
Contraception: trying to suppress HPG axis so give a more potent type of oestrogen.
State 5 side-effect/risks of HRT.
Breast cancer Coronary heart disease Deep vein thrombosis Stroke Gallstones
How does HRT affect cardiovascular disease risk?
Increased risk of CHD
Dependent on timing of exposure– older patients who are started on HRT have an increased risk of CHD but in younger women there is no increased risk
Name a synthetic prohormone that has oestrogenic, progestogenic and weak androgenic effects.
Tibolone
What is Tibolone used for and what are the risks?
Reduces risk of fracture
Increases risk of stroke
What is raloxifene and how does it work?
It is a selective oestrogen receptor modulator (SERM)
Oestrogenic effects in bone: reduces risk of fracture
Anti-oestrogenic effects in breast + uterus: reduces risk of breast cancer
What are the problems with raloxifene?
It is associated with an increased risk of fatal stroke + VTE
Does not reduce vasomotor symptoms
What is tamoxifen?
Anti-oestrogenic on breast tissue
What is tamoxifen used for?
Treatment of oestrogen-dependent breast tumours + metastatic breast cancers
What is the term given for menopause before the age of 40?
Premature Ovarian Insufficiency
What could POI be caused by?
Autoimmune
Surgery
Chemotherapy
Radiotherapy
What type of oestrogen is in the combined oral contraceptive pill?
Ethinyl oestradiol
What types of progestogen are used in the combined oral contraceptive pill?
Levonorgestral
Norethistrone
What other effect do progestogens have that reduces the chance of conception?
Thickens cervical mucus making it more difficult for sperm to penetrate
When would you use the progesterone only pill?
If oestrogen is contraindicated –if there is an increased risk of thrombosis (oestrogen has pro-coagulant effects)
E.g. smoker, >35 yrs old, migraine with aura
What is an important point to remember about when to take the progesterone only pill?
It must be taken at the same time every day due to its short half life + short duration of action
What 3 things can you use for emergency contraception?
Copper IUD (up to 5 days): affects sperm viability + function + inhibits fertilisation) Levonorgestral (within 72 hrs): high dose progesterone Ulipristal (within 120 hrs): Anti-progestin activity, Delays ovulation by as much as 5 days, Impairs implantation
What is the purpose of hormone replacement therapy?
Control vasomotor symptoms (hot flushes)
What is the action of combined oral contraceptive pills?
Suppress ovulation via negative feedback actions of E + P at hypothalamus/ pituitary
How is the pill taken?
Take for 21 days or 12 weeks
Stop for 7 days
