10. Oral contraceptives, menopause and HRT Flashcards
What is menopause?
• Permanent cessation of menstruation • Loss of ovarian follicular activity • Average age 51 (45-55) • Climacteric: period of transition - regular => oligomenorrhoea => amenorrhoea (more than 12 months - menopause)
What are the symptoms of menopause?
- Hot flushes
- Urogenital atrophy and dyspareunia (difficult/painful sexual intercourse due to vaginal atrophy)
- Sleep disturbance
- Depression
- Decreased libido
- Joint pain
(symptoms usually diminish over time)
How does the hypothalamo-pituitary-gonadal axis change in menopause?
- Low levels of oestradiol and inhibin B due to follicular atresia
- Less negative feedback - gonadotrophin levels (LH + FSH) rise
What are the complications of menopause?
• Osteoporosis - oestrogen is an anabolic hormone, so reduction results in this
- less matrix - predisposition to osteoporotic fractures 10 fold
• Cardiovascular disease
- same risk as men over 70
What is hormone replacement therapy (HRT)?
• Controls vasomotor symptoms (hot flushes)
• Oestrogen (E)
- endometrial proliferation
- risk of endometrial hyperplasia/carcinoma, so combined with progesterone
- only E if hysterectomy
• Progestogens (P)
How can HRT be taken?
• Cyclical - take oestradiol every day, and for the last 12-14 days take some progesterone
• Continuous combined - take a little bit of oestrogen and progesterone every day
• Oestrogen preparations
- Oral oestradiol (1 mg)
- Oral conjugated equine oestrogen (0.625 mg)
- Transdermal (patch) oestradiol (50 mcg/day)
- Intravaginal
Why is oestrogen usually taken as ethinyl oestradiol as an oral contraceptive?
• Oestradiol is well absorbed but has low bioavailability (extensive first pass metabolism)
• Ethinyl oestradiol is semi-synthetic
- ethinyl group protects molecule from first pass metabolism
• You want oestrogen to be potent in an oral contraceptive to suppress the HPG axis, unlike for menopause which is just used to help symptoms
What are the side effects of HRT?
- Breast cancer
- Coronary heart disease (higher when older)
- DVT
- Stroke
- Gallstones
absolute risk is low, but there is a relative risk e.g. family history of breast cancer
What effect does oestrogen and progestins have on lipid profile and endothelial function?
- Oestrogen has beneficial effects
* Synthetic progestins negate these effects
What is tibolone?
- Synthetic prohormone
- Oestrogenic, progestogenic and weak androgenic effects
- Reduces risk of fracture
- Increases risk of stroke
- Possible increased risk of breast cancer
What is raloxifene?
- Selective oestrogen receptor modulator (SERM)
- Tissue selective effects
- Oestrogenic effects in bone - reduced risk of fracture
- Anti-oestrogenic effects in breast and uterus - reduced risk of breast cancer
- Raloxifene is associated with increased risk of stroke and venous thromboembolism (VTE or DVT)
Why is HRT not prescribed to women as a first line treatment of osteoporosis anymore?
- Other treatments like oral bisphosphonates available
* These are not associated with a risk of breast cancer
What is tamoxifen?
- Anti-oestrogenic on breast tissue
* Used to treat oestrogen-dependent breast tumours and metastatic breast cancers
What is premature ovarian insufficiency, the possible causes of it and the treatment?
• Menopause before age 40 • 1% of women • Could be due: - surgery - chemotherapy - radiation - autoimmune • Treated with HRT
What is the combine oral contraceptive?
- P + E
- E - ethinyl oestradiol
- P - levonorgestrel or norethisterone
- Both suppress the hypothalamus and pituitary
- P thickens the cervical mucous (harder for sperm to pass)
- Take for 21 days (or 12 weeks)
