Hormone Replacement Therapy (HRT)

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Hormone Replacement Therapy(HRT)
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Recent MHRA/CHM advice Drug Safety Update 2007
1(2)2-4

• The decision to prescribe HRT should be based on
  a thorough evaluation of the potential benefits
  and potential risks of treatment.
• Healthcare professionals should assess every
  womans overall risk, including cardiovascular
  risk, particularly in those older than 60 years
  who have increased baseline risk of serious
  adverse events.
• Evidence for the risks of HRT in women who had
  premature menopause is limited. However, the
  baseline risk of adverse events in these younger
  women is low, and the balance of benefits and
  risks may be more favourable than in older women.

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Benefits from HRTDrug Safety Update 2007
1(2)2-4

• Menopausal symptoms
• HRT effectively relieves vasomotor symptoms.
• In most cases, 23 years therapy is sufficient,
  but some women may need longer.
• For all women, the lowest effective dose should
  be used for the shortest time.
• Osteoporosis
• HRT is effective for prevention of osteoporosis,
  but its beneficial effect on bone diminishes soon
  after stopping treatment.
• Because of the risks associated with long-term
  use, HRT should be used for prevention of
  osteoporosis only in women who are unable to use
  other medicines that are authorised for this
  purpose.

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Effects on fracture of the femurDrug Safety
Update 2007 1(2)2-4
From placebo group in oestrogen-only arm of WHI
From placebo group in oestrogenprogestogen arm
of WHI
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Harms from HRT cancersDrug Safety Update 2007
1(2)2-4

• Breast cancer
• The risk of breast cancer is increased in women
  who take HRT for several years.
• Combined HRT has been associated with the highest
  risk.
• For oestrogen-only HRT, risk is lower than with
  combined HRT. Some studies have not shown an
  increased risk for oestrogen-only HRT.
• Risk increases with duration of use and returns
  to baseline within a few years of stopping
  treatment.
• HRT, especially combined therapy, may increase
  mammographic density, which may adversely affect
  radiological detection of breast cancer.
• Ovarian cancer
• Observational studies suggest that long-term use
  of oestrogen-only or combined HRT may be
  associated with a small increased risk of ovarian
  cancer.
• Risk returns to baseline a few years after
  stopping treatment.

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Effects on cancersDrug Safety Update 2007
1(2)2-4
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Harms from HRT CV disease (1)Drug Safety
Update 2007 1(2)2-4

• Coronary heart disease (CHD)
• RCTs found increased CHD risk in women who
  started combined HRT more than 10 years after
  menopause.
• Very few RCTs have assessed younger, newly
  menopausal women, and some have suggested a lower
  relative risk in these women compared with older
  women.
• The low baseline risk of CHD in most younger
  women, and the very low attributable risk due to
  HRT, means that their overall CHD risk is likely
  to be low.
• No increased risk of CHD with use of
  oestrogen-only HRT has been identified to date.
• Importantly, there are no data from RCTs to
  suggest a cardiovascular benefit with
  oestrogen-only or combined HRT.
• Healthcare professionals should assess carefully
  every womans risk of CHD before prescribing HRT,
  irrespective of her age or time since menopause.

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Harms from HRT CV disease (2)Drug Safety
Update 2007 1(2)2-4

• Stroke
• Increased risk of stroke (mostly ischaemic) with
  oestrogen-only and combined HRT.
• Increase in relative risk similar irrespective of
  age.
• Baseline risk of stroke increases with age and
  therefore older women have a greater absolute
  risk.
• Limited observational data suggest that stroke
  risk may depend on oestrogen dose.
• Venous thromboembolism (VTE)
• Oral HRT increases the risk of VTE (DVT or PE).
• Events are more likely in the first year of use.
• Risk appears higher with combined HRT than with
  oestrogen-only HRT.
• Risk associated with other routes of
  administration not established, but it may be
  lower with transdermal HRT.

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Effects on CVDDrug Safety Update 2007 1(2)2-4
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Alternatives to HRTCKS guidance. January 2008

• For many women, lifestyle adjustments, education,
  and reassurance may be sufficient.
• Vaginal lubricants and vaginal moisturizers can
  help ease vaginal dryness and related symptoms.
• Other potential treatments for menopausal
  symptoms include tibolone, clonidine, various
  antidepressants and testosterone.
• Complementary therapies are widely used, but are
  not recommended
• few efficacy or safety data available
• some herbs e.g. soy foods, gingseng, black cohosh
  and red clover have oestrogenic properties
• Black cohosh also possibly associated with
  hepatic impairment
• EMEA Committee on Herbal Medicinal Products
  (HMPC) www.emea.europa.eu/pdfs/human/hmpc/26925806
  en.pdf

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Benefits and risks of tiboloneDrug Safety Update
2007 1(2)5-6

• Benefit-risk balance in licensed indications
• In younger women, the risk profile of tibolone is
  broadly similar to that for conventional combined
  HRT.
• For women older than about 60 years, the risks
  associated with tibolone start to outweigh the
  benefits because of the increased risk of stroke.
• Before starting tibolone, every womans overall
  risk of stroke, breast cancer, and, in those with
  an intact uterus, endometrial cancer should be
  assessed carefully, taking into consideration any
  baseline risk factors, the increased risk due to
  tibolone use, and her therapeutic preferences.
• Healthcare professionals should weigh the
  increased risk of stroke with tibolone against
  the increased risk of breast cancer with combined
  HRT for women with a uterus.

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Results from the WHI trialJAMA 2002288321-33
HR for HRT vs. Placebo (95CI) Events per 10,000py for placebo Events per 10,000py for HRT Excess events per 10,000 py
CHD (non-fatal MI CHD death) 1.29 (1.02-1.63) 30 37 7
Stroke 1.41 (1.07-1.85) 21 29 8
Breast cancer 1.26 (1.00-1.59) 30 38 8
VTE 2.11 (1.58-2.82) 16 34 18
Hip fracture 0.66 (0.45-0.98) 15 10 -5
Colorectal cancer 0.63 (0.43-0.92) 16 10 -6
Total mortality 0.98 (0.82-1.18) 53 52 NS
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Summary

• 80 of women experience menopausal symptoms and
  45 find them distressing.
• For many women, lifestyle adjustments, education,
  and reassurance are sufficient.
• HRT is the main treatment
• Tibolone is an alternative, but note risks and
  benefits.
• For individual women, need to weigh benefits of
  HRT against side-effects.
• Reassess appropriateness of treatment annually
• Treatment longer than 5 years needs careful
  thought.