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PH2501- pharmacology > Lec 48- Hormone replacement therapy > Flashcards

Lec 48- Hormone replacement therapy Flashcards

1
Q

The Menopause

A 
-Progressive decline in ovarian function 
\+2-3 years 
-Symptomology due to loss of oestrogen 
\+Natural decline 
\+Oophorectomy- removal of one or both ovaries 
-Marked by end of menstruation 
\+12 months after last period 
-FSH high, oestrogen low
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2
Q

Symptomology

A

-Vasomotor disturbances
+Flushing, peripheral vasodilation
+Nocturnal sweating and sleep problems
+Headaches
-Urogenital atrophy
+Wall of vagina thins and glands atrophy- reduced mucous
+Similar changes in urethra and bladder- frequency and dysuria

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3
Q

Symptomology continued

A

-Psychological effects
+Memory
+Mood
+Long term neurodegeneration- Alzheimers
-Osteoporosis
+Bone density, decrease deterioration of structure
+Risk factos: White, smoker, low physical exercise and inadequate Ca in diet
+Fractures

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4
Q

HRT

A

-Replacement of hormones
+Oestrogen
+Loss gives rise to symptoms
+Risk of endometrial hyperplasia and carcinoma: Synthesised natural oestrogens, natural oestrogens from equine sources
-Progesterone: Used in comboination
+Used in women with intact urterus
+Withdrawl from progesterone causes bleeding

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5
Q

Benefits of HRT

A

-VAsomotor and psychological
+Reduction in flushing, sleep problems, sweats, headachesa and palpatations
+Very distressing`; psychological benefit when reducing
-Urogenital ageing
+Reduction in vaginal dryness as welll as vaginal and urethral infections
+Reduction in Dysuria and urinary frequency
-Replacingg oestrogen helps regardless of route of admin

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6
Q

Benfits of HRT continued

A 
Oesteoporosis 
-HRT delays bone loss and increases bone density in hip and spine 
\+But needs to be taken for 7-10 years 
-Effects wane rapidly on cessation 
-Oral and transdermal equally effective
\+Oral oestradiol= 2mg 
\+Oral conjugated oestrogens=625 mcg
\+Transdermal estradiol 
-Long term therapy licensed for prevention of oesteoporosis
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7
Q

Benefit of HRT (3)

A

Colorectal cancer
-Reduction in incidence dependant on age of cohort and duration of treatment
+Per 1000
+Age 50-9 NoHRT=3, HRT=2
+Age 60-9 NoHRT=8, HRT= 3
Coronary heart disease
-Normal incidence rises post menopause (=men by 65)
-Many studies: but difficult to control all other factors
-Protective effects lie with oestrogen
-Progesagen may reduce benefits (theoretically)
-Most benefit for women without a uterus

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8
Q

Benefit of HRT (4)

A 
Short term 
-Symptom relief 
Long term 
-Osteoporosis 
-CHD 
-Colorectal cancer
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9
Q

Risks of HRT- endometrial cancer

A

Endometrial cancer
-In women with intact uterus
-During and after
-Unless taken with adequate levels of progesterone
+For 10-13 days per cycle
+Or continuous combo (not for perimenopause): irregular bleeding
-NB- combo therapy is not necessary following a hysterectomy

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10
Q

Risk of HRT- Breat cancer

A
  • BNF 42: CSM warning
  • Increased risk related to duration of therapy
  • Returns to normal 5 years post HRT
  • 45 cases/1000 50 year olf non-HRT
  • +2 cases in women taking HRT for 5 years
  • +6 cases in women taking HRT for 10 years
  • +12 cases for women taking HRT for 15 years
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11
Q

Putting in context

A

-All types of HRT included
-Risk may well be largely or wholly causal
+Sub analysis of many possible contributing factors
-For women who use HRT for 5 years from age of about 50
+1 extra ovarian cancer per 1000 users
+1 extra ovarian cancer death per 1700 users

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12
Q

Risk of HRT- VTE

A

-HRT use causes a 2-3 fold increase in risk of VTE
+Causes double of risk of pulmonary embolism
-Risks greatest during first year
+Return to normal after 1 year of continuing HRT use
-Oral route MAY have higher risks
NB- Surgery, other risk factors

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13
Q

Risk of HRT- Weight gain

A
  • Weight gain and breast tenderness found in the short term
  • No significant effects long term
  • Fear of weight gain deters HRT Use
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14
Q

Last years news- Long term use

A

-Reduction in CHD NOT evident
-July 2005- US WHI stopped
+16,608 women, 5.2 follow up
-Found slight increase in CHD
-November 2005: Wisdom trial stopped
+Started 1999
+Womens international study of long term oestrogen after menopause
-Study in rats suggests long term HRT in Alzheimers may worsen memory
-This and clinical studies suggest
+Beneficial effects of short term HRT
+Particular benefit in very aged
-BUT beneficial effect reduced or reverse on long term HRT

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15
Q

Million women study

A 
-Published in Lancet, August 2003 
\+1,084,110 women 50-64 
\+Recruited between 1996-2001 
-Increased risk of breast cancer 
-Current users of combined HRT 
-Oestrogen only HRT 
-Tibolone
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16
Q

Current recommendations for use

A

-SYMPTOMATIC RELIEF
+Usually 2-3 years
+Benefits outweigh risks
-Longer term prevention of disease
+Licensed for prevention of osteoporosis
+Should NOT be prescribed for prevention of CHD
+Alternative treatments for oesteoporosis considered
+Individual risk benefit appraised and reappriased at least once yearly during therapy

17
Q

Oestrogens for HRT- Oral

A

-Easy, well tolerate , first choice
-Alone or with progesterone
+Undergoes extensive first pass metabolism= Need Alternative route
-Because of its effects on liver, oestrogen promotes synthesis and secretion of
+Coagulation factors and renin substrates- detrimental to health
+Lipid apoproteins - beneficial to health

18
Q

Oestrogen’s for HRT

A

Transdermal and sub-cut
-Avoid first pass metabolism- liver problems or raised triglycerides
-Preparations may only contain oestrogen- need to add progesterone
SUBCUTANEOUS implants
-COmpliance and good symptoms control
+Need to monitor oestrogen serum levels before each implant- tachyphylaxis leading to overdosage
LOCAL- urogenital symptoms
-Pessaries, creams, vaginal tablets, ring
-If needed> a few weeks add oral progesterone

19
Q

Progesterone’s for HRT

A 
Syntheitc progestrogens used 
-Progesterone like 
\+Hydroxyprogesterone, medroxy progesterone acetate, dydrogesterone, megestrol acetate 
-Testosterone derivatives 
\+Noesthisterone, ethyndiol 
-NOT subject to first pass metabolism 
-Orally available 
\+Transdermal available (w/oestrogen) and vaginal gel
20
Q

Tibolone

A

-Has oestrogenic, progestogenic and weak adrogenic activities
+Licenced for VASOMOTOR symptoms and for prophylaxis of osteoporosis
-Does NOT stimulate endometrium
+NO need for progesterone
-Stabalises hypothalamic function after cessation of ovarian function
+NO benefit durin PERImenopause
+Used 12 month after last period

21
Q

HRT is NOT A CONTRACEPTIVE

A

-Women may be fertile for 2 years after there last period if they are under 50

22
Q

Different effects on bleeding pattern

A

-Continuous combination therapy
+No irregular bleeding possible, especially during early treatment
-Oestrogen continuous PLUS progestagen for 10-14 days per cycl
+Expect regular withdrawal bleeding
+NB NO uterus= NO bleeding

PH2501- pharmacology (47 decks)

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