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Exam 2- Endocrinology and cancer > Hormone replacement therapy (HRT) > Flashcards

Hormone replacement therapy (HRT) Flashcards

1
Q

What is HRT?

A

Hormone replacement therapy

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2
Q

What is menopause?

A

The permanent cessation of menstruation resulting from loss of activity of the ovarian follicles.
Occurs after 12 months amenorrhoea

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3
Q

What is the mean age for menopause?

A

51 years

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4
Q

What is the process of menopause?

A
  • 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
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5
Q

What are the three phases of menopause?

A
  • Phase 1: Perimenopause
  • Phase 2: Premature menopause
  • Phase 3: Post menopause
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6
Q

What happens in the perimenopause phase of menopause?

A
  • 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
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7
Q

What is premature menopause?

A
  • 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
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8
Q

What is post-menopause?

A

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

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9
Q

What are the short-term symptoms of the menopause?

A
  • 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
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10
Q

What are the long-term symptoms of menopause and what causes them?

A

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

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11
Q

What is the aim of hormone replacement therapy?

A
  • To replicate hormone levels from before menopause.
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12
Q

What are the two types of HRT?

A
  • Oestrogen
  • Oestrogen and progestogen
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13
Q

When is oestrogen + progestogen HRT used?

A

In most cases- for women who have an intact uterus

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14
Q

Why is progestogen needed in HRT for women with an intact uterus?

A
  • 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
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15
Q

When is just oestrogen HRT used and why?

A

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

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16
Q

Why are natural oestrogen preferred over synthetic oestrogen for HRT?

A

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

17
Q

What is the consequence of preferred use of natural oestrogen over synthetic?

A
  • 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
18
Q

For what duration of the cycle is progestogen needed?

A

For a minimum of 10 days per 28 day cycle

19
Q

Describe the sequential combined oral regime of HRT?

A
  • 28 days of oestrogen
  • 12-14 days of progestogen
  • no interval- bleed every 4 weeks
  • used in perimenopausal stage
  • e.g. Elleste-duet
20
Q

Describe the Tricyclic combined oral regime of HRT?

A
  • 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
21
Q

Describe the continuous combined oral regime of HRT?

A
  • 28 days of oestrogen
  • 28 days of progestogen
  • repeat without interval
  • no bleed
  • used in postmenopausal women
  • e.g. Premique
22
Q

What are the benefits of giving HRT by transdermal route as opposed to oral?

A
  • 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)
23
Q

What is the recommended first line treatment for women with an increased risk of developing venous thromboembolism?

A

HRT given via a transdermal route

24
Q

Who have an increased risk of Vte?

A

Women with:
- BMI >30
- Previous family history of vte
- Have had vet previously

25
Q

When are vaginal oestrogen formulations used as HRT?

A
  • If the womens predominant menopausal symptoms are vaginal or/and bladder related
  • or if also on systemic HRT and have vaginal symptoms
26
Q

What medication has recently become available OTC for HRT?

A

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

27
Q

When is HRT reviewed?

A
  • 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
28
Q

What are some possible side effects of HRT as a result of oestrogen?

A
  • 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.

29
Q

What are some possible side effects of HRT as a result of progestogen?

A
  • 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
30
Q

Why is compliance with HRT low?

A
  • side effects caused by the progestogen
  • regular monthly bleeds as a result of the combination therapy when patient’s periods were stopping
  • Weight gain
31
Q

What are the benefits of taking HRT?

A
  • 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
32
Q

How long does HRT have beneficial impacts on the risk of osteoporosis?

A
  • 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
33
Q

What are the risks/disadvantages of taking HRT medication?

A
  • 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
34
Q

What is the MHRA recommendation for prescribing HRT?

A
  • 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
35
Q

What are some alternatives to HRT for symptom management?

A
  • 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

36
Q

What are some examples of the oestrogen and progestogen used in HRT?

A

Oestrogen- Estradiol, Estrone
Progestogen- Less androgenic (more commonly used) e.g. Medroxyprogestogen acetate, Dydrogesterone or more androgenic e.g. Norethisterone or levonorgestrel

Exam 2- Endocrinology and cancer (28 decks)

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