10. Oral Contraceptives, Menopause and HRT Flashcards
Menopause definition
Permanent cessation of menstruation
- Loss of ovarian follicular activity
- Average age 51
Climacetric syndrome
A period of transition:
- You have normal regular cycles every month followed by oligomenorrhoea, which eventually progresses to amenorrhoea
- Amenorrhoea of more tha 12 months is menopause
Symptoms of Menopause
- Hot flushes
- Urogenital atrophy and dyspareunia (difficult or painful sexual intercourse due to vaginal atrophy)
- Sleep disturbance
- Depression
- Decreased libido
- Joint pain
Changes to the hypothalamo-pituitary-gonadal axis in menopause
- Low levels of oestradiol and inhibin B because of the follicular atresia
- Less negative feedback so rise in gonadotrophin levels
- So youd expect LH and FSH to be high
Complications of Menopause
1. Osteoperosis
- Caused by oestrogen deficiency
- An anabolic hormone
- 10 fold increase in the risk of fracture in post menopausal women
2. Cardiovascular Disease
- Proctected against CVD before menopause but same risk as men after
Hormone replacement therapy to control hot flushes
Give oestrogen:
- Endometrial proliferation increases the risk of endometrial carcinoma
So combine with progesterone:
- Prevents endometrial hyperplasia
In the case of a hysterectomy you can give oestrogen only since you dont need to worry about the endometrium
Formulations of HRT
- Cyclical- take oestradiol every day and for the last 12-14 days you take some progesterone
- Continuous combined- Take a bit of oestrogen and progesterone every day
Oestrogen preparations:
- Oral oestradiol (1mg)
- Oral conjugated equine oestrogen (0.625 mg)
- Transdermal (patch) oestradiol
- Intravaginal
Bioavailabilty of oestradiol
Well absorbed but has a low bioavalibility (extensive first pass metabolism)
Alternative oestrogens
- Oestrone sulphate (conjugated oxygen)
- Ethinyl oestradiol: semi synthetic oestrogen used in the oral contraceptive ethinyl group protects the molecule from metabolism
Side effects in HRT in menopause
- The absolute risk of complications for healthy women using the treatment is very low, however there is a relative risk:
- Breast cancer
- venous thromboembolism
- Stroke
- Gallstones
Risk of CHD after HRT
There is an increased risk after the age of 60:
- It is about timing of exposure: you can reassure the younger women (in their 50s) that the absolute risk is very small but have some consideration for the people who have risk factors for breast cancer, heart disease, stroke etc.
Use of Tibolone in menopause
- Synthetic prohormone
- HAs oestrogenic, progestonic and weak adrogenic efects
- REDUCES THE RISK OF FRACTURE
- Does increase risk of stroke
Use of raloxifene in menopause
- Selective oestrogen receptor modulator
- Tissue selective:
- In bone- reduces risk of fracture
- In breast and uterus- has anti-oestrogenic effects- reduces cancer risk
- Associated with an increased risk of fatal stroke
Use of tamoxifen in menopause
- Anti-oestrogenic on breast tissue
- Used to treat oestrogen-dependent breast tumours and metastatic breast cancers
Premature ovarian insufficiency
Menopause occuring before the age of 40
Occurs in 1% of women
Requires treatment via HRT- bones need protection
Could be due to:
- Autoimmune
- Surgery
- Chemotherapy
- Radiation
