Oral Contraceptives, Menopause and HRT Flashcards
What is menopause?
Permanent cessation of menstruation
- Loss of ovarian follicular activity
- Confirmed after 12 months of amenorrheoa
NOTE: The average age is 51 years (age range: 45-55)
What is the term given to the period of transition just before menopause? Describe this period of transition.
Climacteric period
- Normal cycles → irregular cycles (oligomenorrhoea) → amenorrhoea
- So essentially the irregular cycles are charactertistic of the climacteric period
State some symptoms of menopause.
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Hot flushes (vasomotor symptoms)
- Sudden feelings of heat that spread through head, neck and upper chest
- Drop in oestrogen leads to hormonal imbalance and disruption in thermoregulation
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Urogenital atrophy
- leads to dyspareunia = difficult or painful sexual intercourse
- Lack of oestrogen causes thinning of vaginal walls and drying of secretions as these are maintained by oestrogen
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Lack of oestrogen also affects bladder control:
- Lining of your urethra, the tube that empties urine from your bladder, begins to thin.
- Pelvic floor muscles, which support urethra and bladder, weakens.
- Sleep disturbance
- Can be due to hot flushes
- Lack of oestrogen causes hormonal imbalance which can affect melatonin levels and impact sleep
- Decreased libido (sex drive)
- Depression
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Decline in oestrogen leads could affect NT levels in the brain
- Oestrogen enhances levels of NA, serotonin, dopamine which influence mood
- Sleep disturbance would also affect mood
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Decline in oestrogen leads could affect NT levels in the brain
- Joint pain
- Oestrogen is responsible for regulating fluid levels in the body
- Low oestrogen meansbody becomes less able to hold water
- This can affect the hydration and lubrication of the joint tissues, including the cartilage, ligaments and tendons
- This reduces flexibility of joints causing stiffness
- Less lubrication and more friction can lead to tissue damage causing pain and inflammation
What do the ovaries produce that feeds back on the HPG axis?
Oestradiol and Inhibin B
- These inhibit LH and FSH from the anterior pituitary AND GnRH from the hypothalamus
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 B
- This means that there is less negative feedback on the HPG axis
- Therefore, you get an increase in LH and FSH levels
NOTE: You wouldn’t really get an increase in GnRH as LH and FSH would be inhibiting GnRH release by negative feedback
What are the main complications of menopause?
Osteoporosis
- Oestrogen has anabolic effects on bone
- Therefore, oestrogen decline leads to loss of bone density
- This makes bones more brittle and prone to fracture
Cardiovascular disease
- Women are protected against cardiovascular disease before menopause
- Effects of oestrogen on the circulatory sytem are protective against CVD
- They have the same risk as men by the age of 70
What is HRT primarily for?
The control of vasomotor symptoms = hot flushes
- Temperature regulation is often linked to constriction/dilation of blood vessels (i.e. vasomotor)
What are the risks of giving oestrogen as part of HRT?
Endometrial hyperplasia → increases the risk of endometrial carcinoma
- Oestrogen stimulates thickening of endometrium
- Hyperplasia = increase in cell number
- This would be due to increased cell division so the cell cylce regulation is already a bit off which means it is more prone to become completely dysregulated by a mutation (cancerous state)
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
- Progesterone has anti-mitogenic effects (i.e. ani-mitosis), so counteracts the mitogenic effects of oestrogen
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 risk of oestrogen stimulating endometrial hyperplasia (i.e. no endometrium to be stimulated)
Describe the 2 different formulations of HRT.
Cyclical:
- Take oestogen every day
- Then for the last 12-14 days you take progesterone
Combined continuous
- Take oestrogen and progesterone together every day
State 4 different types of oestrogen preparations.
- Oral oestradiol (1 mg)
- Oral conjugated equine oestradiol (0.625 mg)
- Transdermal (i.e. patch) oestradiol (50 mcg/day)
- Intravaginal
What are the different types of oestrogens?
- Oestradiol
- Oestrone sulphate (‘conjugated’ oestrogen)
- Ethinyl oestradiol
The first two are produced endogenously
Ethinyl oestradiol is semi-synthetic (i.e. formed by the chemical conversion a naturally occurring product - here oestradiol)
Describe the absorption and metabolism of oestradiol.
- Oestradiol is absorbed well
- However, it has high first pass metabolism so has low bioavailability
- This means that in oral preparations, you must give a high dose of oestradiol
NOTE: Most oestrogens can be administered via transdermal skin patches as well as orally - direct into systemic circulation to overcome problem of first pass metabolism with oral administration
Name a semi-synthetic oestrogen that’s used in oral contraceptives.
Ethinyl oestradiol
- The ethinyl group protects the drug from first pass metabolism
- Therefore lower dose needed to be administered orally, as bioavailability of this drug is higher - i.e. a greater proportion of the active drug ends up in the systemic circulation
