10 - Oral contraceptives, Menopause and HRT Flashcards
What is menopause?
What is the average age for menopause?
Permanent cessation of menstruation (loss of ovarian follicular activity) - amenorrhoea for more than 12 months
NOTE: usually happens between 45-55 yrs. average = 51
What is the term given to the period of transition just before menopause? Describe this period of transition.
Climacteric period
You go from having normal regular cycles and then it becomes a little irregular (oligomenorrhoea) and then it progresses to amenorrhoea.
State some symptoms of menopause.
- Hot flushes
- Urogenital Atrophy (leads to dyspareunia – difficult or painful sexual intercourse)
- Sleep disturbance
- Decreased libido
- Depression
- Joint pain
Briefly describe the hypothalamic-pituitary-gonadal axis
- GnRH from the hypothalamus stimulates the anterior pituitary to produce LH and FSH
- these stimulate the ovaries to produce oestrodiol and inhibin B
- oestrodiol and inhibin B inhibit FSH and LH secretion (negative feedback at the level of the hypothalamus and pituitary)
What do the ovaries produce that feeds back on the HPG axis?
Oestradiol and Inhibin B
What are the changes in feedback and the HPG axis in menopause?
There is a loss of ovarian follicular activity so you get a decreased production of oestradiol and inhibin
This means that there is less negative feedback on the HPG axis
What would you expect the LH and FSH levels of a menopausal woman to be?
High – because of the loss of oestrogen and inhibin production
What are the main complications of menopause?
Osteoporosis (the protective effect of oestrogen on bone is lost) Cardiovascular disease (women are protected against cardiovascular disease before menopause)
Why is HRT not just given to all post-menopausal women? What is it used for?
controls vasomotor symptoms (disabling hot flushes)
not used for the treatment of osteoporosis
When would HRT NOT be given to a post-menopausal woman?
to someone with ischaemic heart disease or DVT
What are the risks of giving (only) oestrogen as part of HRT?
Endometrial hyperplasia/proliferation, which increases the risk of endometrial carcinoma
How is the risk of endometrial hyperplasia from HRT prevented?
You give progesterone as well as oestrogen
The progesterone blocks this effect of oestrogen on the endometrium and, hence, 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 there is no endometrium to stimulate with oestrogen
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 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 (first pass) 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.
State some side-effect/risks of HRT.
Breast cancer Coronary Heart Disease Deep Vein thrombosis (BCD) Stroke Gallstones
Describe the counteracting effects of oestrogens and progesterones
oestrogen - beneficial effect on lipid profile and endothelial function
synthetic progesterone negates these effects
How does HRT affect cardiovascular disease risk?
increased risk of CHD
The timing of exposure is important in terms of cardiovascular disease risk – older patients starting on HRT have an increased risk of CHD but in younger women there’s no increased risk
Older women are more susceptible to the pro-thrombotic and pro-inflammatory effects of oestrogen
Name a synthetic prohormone that has oestrogenic, progestogenic and weak androgenic effects.
Tibolone
What is tibolone used for and what are the risks?
It reduces the risk of fracture
It increases the risk of stroke
What is raloxifene and how does it work?
- It is a selective oestrogen receptor modulator (SERM)
- In bone it has oestrogenic effects and reduces the risk of fracture (used if other treatments fail in menopausal women with osteoporosis)
- In breast and uterus it has anti-oestrogenic effects and reduces the risk of breast cancer
What are the problems with raloxifene?
It is associated with an increased risk of fatal stroke and VTE
What is tamoxifen?
Anti-oestrogenic on breast tissue
What is tamoxifen used for?
Treatment of oestrogen-dependent breast tumours and metastatic breast cancers
What is the term given for menopause before the age of 40?
Premature Ovarian Insufficiency
Name the possible causes of Premature Ovarian Insufficiency
Autoimmune
Surgery
Chemotherapy
Radiotherapy
What is the treatment for Premature Ovarian Insufficiency?
HRT to protect their bones
What type of oestrogen is in the combined oral contraceptive pill?
Ethinyl oestradiol
What types of progestogen is used in the combined oral contraceptive pill?
Levonorgestral
Norethistrone
What other effect do progestogens have that reduces the chance of conception?
It thickens cervical mucus meaning that it is more difficult for sperm to penetrate it
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)
e.g. smokers, older women, 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
What is the name given to the long-acting intra-uterine progesterone(-only) device?
Mirena
What 3 things can you use for emergency (post-coital) contraception?
- Copper IUD (affects sperm viability and inhibits fertilisation)
- Levonorgestral (within 72 hours – high dose progesterone)
- Ulipristal (within 120 hours)
• Anti-progestin activity
• Delays ovulation by as much as 5 days
• Impairs implantation