Oral Contraceptives, Menopause and HRT Flashcards
What is menopause?
Permanent cessation of menstruation - amenorrhoea for more than 12 months
NOTE: usually happens between 45-55 yrs
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
What do the ovaries produce that feeds back on the HPG axis?
Oestradiol and Inhibin B
How does this feedback change 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
- Oestrogen deficiency
- Loss of bone matrix
- 10-fold increased risk of fracture - Cardiovascular disease
- protected against CVD before the menopause
- have the same risk as men by the age of 70
What are the risks of giving oestrogen as part of HRT?
Endometrial hyperplasia, which increases the risk of endometrial carcinoma
How is this effect of oestrogen prevented?
You give progesterone as well as oestrogen
The progesterone blocks this effect of oestrogen on the endometrium and, hence, prevents endometrial hyperplasia -reduces risk of cancer
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.
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 Venous thromboembolism (VTE) DVT Stroke Gallstones
NOTE:
The absolute risk of complications for healthy symptomatic postmenopausal women in their 50s taking HRT for five years is very low.
How does HRT affect cardiovascular disease risk?
There is an increased risk of coronary heart disease
The timing of exposure is important in terms of cardiovascular disease risk – older patients who are started on HRT have an increased risk of CHD but in younger women there was no increased risk
Name a synthetic prohormone that has oestrogenic, progestogenic and weak androgenic effects.
Tibolone
What is this drug 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
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
