Menopause, HRT & Oral Contraceptives Flashcards
What is menopause? When does it occur?
Permanent cessation of menstruation (amenorrhoea >12 months) and loss of ovarian follicular activity
Average age 51 (range 45-55)
What is the term given to the transition period into menopause?
Climacteric period
Normal => oligomenorrhoea => amenorrhoea
State some symptoms of menopause
- Hot flushes (head, neck, upper chest)
- Urogenital Atrophy which leads to dyspareunia (difficult or painful sexual intercourse)
- Sleep disturbance
- Decreased libido
- Depression
- Joint pain
- Symptoms usually diminish/disappear with time.
What do the ovaries produce that has a negative feedback effect? How does this feedback change in menopause? What effect does this have?
Oestradiol and inhibin B
Loss of ovarian follicular activity => decreased production of oestradiol and inhibin => less negative feedback => High LH and FSH
State and explain the main complications of menopause
Osteoporosis: loss of the protective effect of oestrogen on bone = loss of bone matrix
Cardiovascular disease: women are protected against cardiovascular disease before menopause
What is the risk of giving oestrogen as part of HRT, and how is this risk prevented?
Causes endometrial hyperplasia, which increases the risk of endometrial carcinoma.
You give progestogens as well to block this effect on the endometrium.
In which subset of patients would you give oestrogen only as part of HRT?
Patients who have had a hysterectomy (no uterus so there is no endometrium)
Describe the 2 different formulations of HRT.
Cyclical = take oestradiol every day, and then for the last 12-14 days you take progesterone
Combined continuous = take a little oestrogen and progesterone every day
State 4 different types of oestrogen preparations
- Oral estradiol (1mg)
- Oral conjugated equine oestrogen e.g. Estrone sulphate (0.625 mg)
- Transdermal (patch) oestradiol (50 microgram/day)
- Intravaginal
Describe the absorption and metabolism of oestradiol, stating why oral doses are higher
Oestradiol is absorbed well but is heavily metabolised in the liver so the bioavailability is very low.
This means that in oral preparations, you must give a high dose of oestradiol.
Name a semi-synthetic oestrogen that’s used in oral contraceptives
Ethinyl oestradiol (The ethinyl group protects the drug from hepatic first pass metabolism)
What is the difference between the types and dose of oestrogen given in HRT compared to the oral contraceptive?
In HRT you are just giving a little bit of oestrogen to prevent the symptoms of menopause.
In contraception, you are trying to suppress the HPG axis so you give a more potent type of oestrogen.
*State some side-effect/risks of HRT
Breast cancer Coronary heart disease Deep Vein thrombosis Stroke Gallstones
*Note: absolute risk of complications for healthy symptomatic postmenopausal women in their 50s taking HRT for five years is very low
What influences the risk of coronary heart disease following postmenopausal HRT?
Timing of exposure
- No excess risk in younger menopausal women (50-59)
- In older women (>60), susceptible to prothrombotic &
proinflammatory effects of oestrogen
Name a synthetic prohormone that has oestrogenic, progestogenic and weak androgenic effects.
Tibolone
State the effects of using tibolone
It reduces the risk of fracture
It increases the risk of stroke
What is raloxifene and what does it do?
It is a selective oestrogen receptor modulator (SERM)
- In bone it has oestrogenic effects and reduces the risk of fracture
- In breast and uterus it has anti-oestrogenic effects and reduces the risk of breast cancer
What are the problems with raloxifene?
- It does not reduce vasomotor symptoms (hot flushes)
- It is associated with an increased risk of fatal stroke and venous thromboembolism
What is tamoxifen, and what is it used for?
It is an anti-oestrogenic on breast tissue.
Used to treat oestrogen-dependent breast tumours & metastatic breast cancers
What is Premature Ovarian Insufficiency? List some causes
Menopause before the age of 40
Autoimmune
Surgery
Chemotherapy
Radiation
What type of oestrogen and progestogen is used in the combined oral contraceptive pill?
Oestrogen - ethinyl oestradiol
Progestogen - levonorgestrel or norethisterone
State the purpose of oral contraceptives, and how is this achieved? When do you take the pill?
Suppress ovulation
- Oestrogen + progestogen has negative feedback actions at hypothalamus/pituitary
- Progestogen thickens cervical mucus preventing sperm entry into the uterus
Take for 21 days (or 12 weeks), stop for 7 days
When would you use the progesterone-only pill?
If oestrogen is contraindicated – this is if there is an increased risk of thrombosis (oestrogen has pro-coagulant effects)
What is an important point to remember about when to take the progesterone-only pill?
Must be taken at the same time each day
- Short half-life
- Short duration of action
How may long acting preparations of the progesterone-only pill may be given?
Via an intra-uterine system (device called Mirena)
- Provides long term contraception
What 3 things can you use for emergency (post-coital) contraception?
Copper intrauterine contraceptive device that affects sperm viability and function, and inhibits fertilisation (Effectiveness not reduced in overweight/obese women)
Levonorgestral (within 72 hours after intercourse)
Ulipristal (within 120 hours after intercourse):
- Has anti-progestin activity
- Delays ovulation by as much as 5 days
- Impairs implantation
In younger women (50-59), synthetic progestins have what effect on the oestrogen they are combined with?
Oestrogen has beneficial effects on lipid profile &
endothelial function but synthetic progestins negate these effects.
