Hormone replacement therapy (HRT) Flashcards
What is HRT?
Hormone replacement therapy
What is menopause?
The permanent cessation of menstruation resulting from loss of activity of the ovarian follicles.
Occurs after 12 months amenorrhoea
What is the mean age for menopause?
51 years
What is the process of menopause?
- Number of eggs decrease to 0
- this causes follicular activity to fail
- This leads to a fall in oestrogen levels- this is what causes the symptoms
- The negative feedback loop on the pituitary gland starts to fail
- This leads to high levels of FSH and LH= established menopausal pattern of high LH + FSH and low levels of oestrogen
What are the three phases of menopause?
- Phase 1: Perimenopause
- Phase 2: Premature menopause
- Phase 3: Post menopause
What happens in the perimenopause phase of menopause?
- There is a gradual onset of endocrine changes and the ovaries start to fail
- may began to experience hot flushes
- This phase usually lasts approximately 4 years and starts at an average age of 47.5 years
What is premature menopause?
- This is menopause that occurs before the age of 40 years old
- women who experience this are at higher risk of CVD and osteoporosis at a younger age also
What is post-menopause?
This is the phase that occurs 12 months after amenhorea
- this can be difficult to identify especially in those on HRT
- Estimated by the age of 54, 80% of women are post-menopausal
What are the short-term symptoms of the menopause?
- Irregular periods- changes in cycle length
- changes in blood loss
- 80% experience vasomotor symptoms- hot flushes, night sweats, palpitations
- psychological- mood changes, irritability, sleep problems, depression, decreased sex drive
- musculoskeletal- joint and muscle pain
- Vaginal- vaginal dryness, pain on intercourse (dyspareunia)
- urinary- recurrent UTIs, incontinence especially on coughing or sneezing
What are the long-term symptoms of menopause and what causes them?
These side effects are the consequence of the loss of the positive effects of oestrogen.
- negative effect on bone mass- osteoporosis- loss of calcium from bones causes increase in fractures
- negative effect on blood lipid profile- increased risk of CVD
- negative effect on blood coagulation and fibroblytic activity
What is the aim of hormone replacement therapy?
- To replicate hormone levels from before menopause.
What are the two types of HRT?
- Oestrogen
- Oestrogen and progestogen
When is oestrogen + progestogen HRT used?
In most cases- for women who have an intact uterus
Why is progestogen needed in HRT for women with an intact uterus?
- Progestogen is needed to prevent over-stimulation of the endometrium by unopposed oestrogen.
Overstimulation of the endometrium is associated with an increased risk of endometrial cancer
When is just oestrogen HRT used and why?
For women WITHOUT an intact uterus e.g. if they have had a hysterectomy
- progestogen is not needed as there is no endometrium to overstimulate
Why are natural oestrogen preferred over synthetic oestrogen for HRT?
Synthetic oestrogenen are up to 200x more potent and therefore can cause serious side effects e.g.
- adverse lipid profike
- hypertension
- increased risk of abnormal blood clotting
What is the consequence of preferred use of natural oestrogen over synthetic?
- As natural oestrogen is less potent, it is ineffective for contraception and therefore a women may be fertile for:
2 years after last period if less than 50
1 year after last period if greater than 50
As a result, women under 50 can be given a low dose combined oral contraceptive.
Women over 50 should use non-hormonal contraception
For what duration of the cycle is progestogen needed?
For a minimum of 10 days per 28 day cycle
Describe the sequential combined oral regime of HRT?
- 28 days of oestrogen
- 12-14 days of progestogen
- no interval- bleed every 4 weeks
- used in perimenopausal stage
- e.g. Elleste-duet
Describe the Tricyclic combined oral regime of HRT?
- 70 days of oestrogen
- 14 days of progestogen
- then placebo for 7 days
- bleed every 3 months
- used in borderline post-menopausal stage
- e.g. Tridestra
Describe the continuous combined oral regime of HRT?
- 28 days of oestrogen
- 28 days of progestogen
- repeat without interval
- no bleed
- used in postmenopausal women
- e.g. Premique
What are the benefits of giving HRT by transdermal route as opposed to oral?
- Less day to day variation in blood levels
- Produces a more natural physiological oestradiol:oestrone (?) ratio
- bypasses first level metabolism= has less effect on closing factors produced by the liver
- can therefore be given in a smaller dose
- lower risk of venous thromboembolism (VTe)
What is the recommended first line treatment for women with an increased risk of developing venous thromboembolism?
HRT given via a transdermal route
Who have an increased risk of Vte?
Women with:
- BMI >30
- Previous family history of vte
- Have had vet previously
When are vaginal oestrogen formulations used as HRT?
- If the womens predominant menopausal symptoms are vaginal or/and bladder related
- or if also on systemic HRT and have vaginal symptoms
What medication has recently become available OTC for HRT?
Gina - 10mcg vaginal tablets (Estradiol)
these are licensed for vaginal symptoms due to oestrogen deficiency in post-menopausal women who are:
- older than 50
- not had a period for over 1 year
given at a dose of 1 vaginal tablet OD for 2 weeks, then a maintenance dose of twice weekly
When is HRT reviewed?
- Initial review at 3 months of taking the medication to assess efficacy and tolerability
- Then will be reviewed annually due to an increased risk of side effects including strokes, breast or endometrial cancer and venous thromboembolisn
What are some possible side effects of HRT as a result of oestrogen?
- nausea and vomiting
- abdominal cramps and bloating
- weight gain
- breast tenderness and enlargement
- pre-menstrual like syndrome
- sodium and fluid retention
women are encouraged to persist with treatment for 3 months as side effects are usually short-lived.
What are some possible side effects of HRT as a result of progestogen?
- in more androgenic drugs- greasy hair and skin
- offset the positive effect on the lipid profile of oestrogen
- in less androgenic drugs- abdominal bloating, mood changes such as irritability, depression
- breast tenderness
Why is compliance with HRT low?
- side effects caused by the progestogen
- regular monthly bleeds as a result of the combination therapy when patient’s periods were stopping
- Weight gain
What are the benefits of taking HRT?
- Control of symptoms e.g. hot flushes, headaches, urinary and vaginal symptoms, mood changes
- decreased risk of osteoporosis- as oestrogen rebalances bone resorption and formation
How long does HRT have beneficial impacts on the risk of osteoporosis?
- Only while the patient is taking HRT
- To prevent fractures long-term, HRT would need to be taken forever, so consider switching to a bisphosphonate when HRT is not appropriate e.g. alendronate
What are the risks/disadvantages of taking HRT medication?
- The risk of venous thromboembolism (VTE) is increased, especially in the first year of use
- Systemic HRT increases the risk of breast cancer after 1 year of use (combined proposes more of a risk than oestrogen only). Risk stops after stopping hrt but remains higher for 10 years after
-Endometrial cancer- only in oestrogen-only hrt
as the progestogen reduces this risk. the risk is eliminated entirely if progestogen is used continuously - Ovarian cancer- with both types of HRT, risks stops after stopping HRT
- Strokes- increase with age anyway but addition of HRT (both types) increases this risk further
- Coronary heart disease- evidence is inconclusive
What is the MHRA recommendation for prescribing HRT?
- Prescribe the lowest effective dose for the shortest effective duration
- Dont prescribe in healthy women with no symptoms only if the benefit of relieving symptoms outweighs the risk
What are some alternatives to HRT for symptom management?
- Tibolone: A synthetic steroid derivative of norethisterone that has oestrogen, progestogen and androgenic activity
Taken at a dose of 2.5mg OD for relief of menopause symptoms and osteoporosis prophylaxis
has similar cautions and contraindications to HRT - Clonidine- a vasodilator used to treat vasomotor symptoms such as hot flushes and sweats. is an alpha-adrenergic agonist and is thought to decrease noradrenergic activity in blood vessels to decrease hot flushes
- given at a dose of 50mcd bd (may be increased to 75mcg after 2 weeks)
unlicensed treatments include: SSRIs, gabapentin and pregablin
Anecdotal evidence:
- St john’s wort- is an enzyme inducer though so interacts significantly with conventional medications
- Phytoestrogen-containing products e.g. black cohosh or red clover. Black cohosh can cause liver impairment though and red clover interacts with drugs such as warfarin
What are some examples of the oestrogen and progestogen used in HRT?
Oestrogen- Estradiol, Estrone
Progestogen- Less androgenic (more commonly used) e.g. Medroxyprogestogen acetate, Dydrogesterone or more androgenic e.g. Norethisterone or levonorgestrel
