1. Seminário da Licenciatura em
Ciências Biomédicas
Diana Catarina Santos nº23271

2. Ovulation does
• Degeneration of not occur
women’s last
oocytes • There is no
corpus luteaum
• There is no follicular • FSH has a drastic
development
development increase
<[progesterone]
< [estrogens]
Diana Catarina Santos nº23271 07-07-2011
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3. Hot flashes;
Palpitations; Anxiety;
Night sweats. Insomnia;
Urogenital
Mood change; infections;
Cardiovascular
Vagina dryness; disease (CVD);
Poor memory.
Loss of libido Osteoporosis;
Alzheimer
Diana Catarina Santos nº23271 07-07-2011
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4. • Unopposed estrogen therapy - women with uterus – continuous
ET proliferation of endometrium – hyperplasia – endometrial cancer
• ET (eg: CEE) must only be used by hysterectomized women
• Combined hormone therapy uses a progestin plus estrogens to
CHT oppose them effects (eg: CEE+MPA)
• Can postmenopausal women trust in HRT? What are the risks?
• To answer the questions there were performed several randomized
clinical trials (RCTs) and observational studies
Diana Catarina Santos nº23271 07-07-2011
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5. Expectations Results
• Climacteric symptoms relief
• Climacteric symptoms relief
• Osteoporosis prevention
• Osteoporosis prevention
• Increase of stroke risk and CVD
• CVD prevention
• Increase of breast cancer risk
Diana Catarina Santos nº23271 07-07-2011
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6. CHT ET
Regiment
Duration of use selection (e.g.:
progestin type)
Diana Catarina Santos nº23271 07-07-2011
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7. Breast cancer risk for users of CHT (CEE+MPA) is higher
than for placebo group
RCTs Women’s Health Initiative (WHI) –> HR=1,26
Heart and Estrogen/Progestin Replacement Study (HERSII) -
> HR=1,30
Breast cancer risk in users of CHT is higher than in never
users
Observational
Million Women Study (MWS)
Studies
Collaborative Group Study –Reanalyzes of 51 studies
Shah Nirav, et al -> estimated the risk of 1,39 fold increase
for observational studies
Diana Catarina Santos nº23271 07-07-2011
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8. Breast cancer risk for users of CHT (CEE+MPA) is increased
in time against placebo group
RCTs 1 year – 8 more cases per 10 000 against placebo group
5,2 years – there are expected 46 more cases per 10 000
than in placebo group
Breast cancer risk for users also appeared to depend
on time Observational
MWS -> RR=1,63 (<5 years) and 2,21 (>5 years) Studies
Diana Catarina Santos nº23271 07-07-2011
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9.  Observational data:
• Studies show that women using CHT sequentially (<15 days/mo) present
lower risk against continuous users;
• Others found an increased risk of 30% against non users for both strategies
of use;
After 5 years of discontinuing the hormonal therapy use, past and
current users have the same relative risk.
Diana Catarina Santos nº23271 07-07-2011
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10. Breast cancer risk for users of ET (e.g.: CEE alone)
presented no raise in the risk of breast cancer compared
with placebo
RCTs
WHI –>HR=0,77 (23% decrease)
Most of studies show a higher breast cancer risk in users
compared with never users Observational
MWS -> RR=1,30 Studies
Collaborative Group Study -> RR=1,34
E3N cohort study-> RR=1,29
Shah Nirav, et al -> estimated the risk of 1,16 fold increase as
a review of observational studies
Diana Catarina Santos nº23271 07-07-2011
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11.  Most observational studies found that:
• Breast cancer increases with the course of time for current users;
• Breast cancer has a higher risk for past users;
• After discontinuation of ET, breast cancer risk decreases;
• Breast cancer risk increase for ET is smaller than the risk that these
studies presented for CHT, according with time.
 Other observational studies presented similar results to WHI studies.
Diana Catarina Santos nº23271 07-07-2011
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12. Invasive lobular carcinoma (ILC) is more difficult to detect by
mammography but have better prognosis than invasive ductal
carcinoma (IDC) [Christopher I., et al]
CHT
• CHT are associated with 2.0 – 3.9 fold increased risk of ILC, but generally
not with IDC.
ET
• Both ILC and IDC risks remain unaltered, even after prolonged use of 25
years.
Diana Catarina Santos nº23271 07-07-2011
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13.  Female primates – Macaca fascicularis
• Breast epithelial proliferation increases –
CEE+MPA high breast cancer risk
• Breast epithelial proliferation increases –
CEE alone high breast cancer risk
• Breast epithelial proliferation is not altered
Tibolone with this therapy
• Significant increase for both ductal and
E2+MPA lobular epithelial proliferation
• Breast epithelial proliferation (ductal and
E2+P4 lobular) remains unaltered
Diana Catarina Santos nº23271 07-07-2011
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14. CHT
leads ET
Abnormal Mammograms are
to: mammograms not compromised
Diagnostic delay
6,9% raise in
breast cancer 2,9% raise in
density breast cancer
Worse tumors and density
increased mortality
Diana Catarina Santos nº23271 07-07-2011
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15.  NHS (Nurses Health Study) and the majority of observational studies
showed a decrease in the risk of death for HRT users compared with never
users;
 These results are expected because:
• Women taking HRT are more under medical supervision;
• Breast cancer can be detected and treated earlier.
 Although observational studies have a lot of limitations:
• They combined CHT and ET results;
• Selection criteria is varied;
• Difference in women’s age (WHI comprised older women)
Diana Catarina Santos nº23271 07-07-2011
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16.  Women taking CEE+MPA (CHT) have a high breast cancer risk, compared with
women taking other HRT or compared with non-users;
 The risk is more apparent with continuous CHT and for ILC;
 Although the differences between RCTs and observational studies ET is
associated with less risk than CHT is;
 Replacing MPA for other progestin may provide more safety for users;
 Mortality is still a controversial.
HRT is associated with a small but significant increase in breast cancer
risk
Diana Catarina Santos nº23271 07-07-2011
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17. Benefits Risks
Quality of life Breast cancer
increase
Osteoporosis
prevention Stroke / CVD
CVD Diagnostic
prevention delay/Mortality
Diana Catarina Santos nº23271 07-07-2011
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