The female genital system encompasses a variety of organs and epithelial
surfaces. Thus diseases affecting organs as diverse as the skin and blood
system can affect this system. Sexually transmitted diseases often get much
of the attention. However, in recent years, infertility issues have predominated.
A pathologist may perform an intraoperative consult opening an ovary or uterus
to determine the nature of the disease process. Leiomyomas (fibroids) of the
uterus and cysts of the ovaries are the two most common conditions requiring
our attention.
| DISEASE ASSOCIATIONS |
CHARACTERIZATION |
| HORMONE REPLACEMENT THERAPY-BREAST CANCER |
|
Relationship between long durations and different regimens of hormone
therapy and risk of breast cancer.
Li CI, Malone KE, Porter PL, Weiss NS, Tang MT, Cushing-Haugen
KL, Daling JR.
Division of Public Health Sciences, Fred Hutchinson Cancer
Research Center, Seattle, Wash.
|
JAMA. 2003 Jun 25;289(24):3254-63. Abstract quote
CONTEXT: Women using combined estrogen and progestin hormone replacement
therapy (CHRT) have an increased risk of breast cancer; however, data
on use for long durations and on risk associated with patterns of use
are lacking.
OBJECTIVE: To evaluate relationships between durations and patterns
of CHRT use and risk of breast cancer by histological type and hormone
receptor status.
DESIGN: Population-based case-control study.
SETTING: Three counties in western Washington State.
PARTICIPANTS: Nine hundred seventy-five women 65-79 years of age diagnosed
with invasive breast cancer from April 1, 1997, through May 31, 1999
(histology: 196 lobular cases, 656 ductal cases, 114 cases with other
histological type, and 9 cases with an unspecified histological type;
estrogen receptor (ER)/progesterone receptor (PR) status: 646 ER+/PR+
cases, 147 ER+/PR- cases, and 101 ER-/PR- cases [6 ER-/PR+ cases and
75 cases with unknown ER/PR status were not included in the analyses
herein]) and 1007 population controls. MAIN OUTCOME MEASURES: Risks
of invasive lobular, ductal, ER+/PR+, ER+/PR-, and ER-/PR- breast carcinomas.
RESULTS: Women using unopposed estrogen replacement therapy (ERT) (exclusive
ERT use), even for 25 years or longer, had no appreciable increase in
risk of breast cancer, although the associated odds ratios were not
inconsistent with a possible small effect. Ever users of CHRT (includes
CHRT users who also had used ERT) had a 1.7-fold (95% confidence interval
[CI], 1.3-2.2) increased risk of breast cancer, including a 2.7-fold
(95% CI, 1.7-4.3) increased risk of invasive lobular carcinoma, a 1.5-fold
(95% CI, 1.1-2.0) increased risk of invasive ductal carcinoma, and a
2.0-fold (95% CI, 1.5-2.7) increased risk of ER+/PR+ breast cancers.
The increase in risk was greatest in those using CHRT for longer durations
(users for 5-14.9 years and >/=15 years had 1.5-fold [95% CI, 1.0-2.3]
and 1.6-fold [95% CI, 1.0-2.6] increases in risk of invasive ductal
carcinoma, respectively, and 3.7-fold [95% CI, 2.0-6.6] and 2.6-fold
[95% CI, 1.3-5.3] increases in risk of invasive lobular carcinoma, respectively.
Associations of similar magnitudes were seen among users of both sequential
and continuous CHRT. Risks of ER+/PR- and ER-/PR- tumors were not increased
by use of any form of hormone replacement therapy; however, small numbers
of these tumors limited power to detect possible associations.
CONCLUSION: These data suggest that use of CHRT is associated with an
increased risk of breast cancer, particularly invasive lobular tumors,
whether the progestin component was taken in a sequential or in a continuous
manner. |
Influence of Estrogen Plus Progestin on Breast Cancer and Mammography
in Healthy Postmenopausal Women: The Women's Health Initiative Randomized
Trial.
Chlebowski RT, Hendrix SL, Langer RD, Stefanick ML, Gass M,
Lane D, Rodabough RJ, Gilligan MA, Cyr MG, Thomson CA, Khandekar J,
Petrovitch H, McTiernan A.
Harbor-UCLA Research and Education Institute, Torrance, Calif.
|
JAMA. 2003 Jun 25;289(24):3243-53. Abstract quote
CONTEXT: The Women's Health Initiative trial of combined estrogen plus
progestin was stopped early when overall health risks, including invasive
breast cancer, exceeded benefits. Outstanding issues not previously
addressed include characteristics of breast cancers observed among women
using hormones and whether diagnosis may be influenced by hormone effects
on mammography.
OBJECTIVE: To determine the relationship among estrogen plus progestin
use, breast cancer characteristics, and mammography recommendations.
DESIGN, SETTING, AND PARTICIPANTS: Following a comprehensive breast
cancer risk assessment, 16 608 postmenopausal women aged 50 to 79 years
with an intact uterus were randomly assigned to receive combined conjugated
equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5
mg/d) or placebo from 1993 to 1998 at 40 clinical centers. Screening
mammography and clinical breast examinations were performed at baseline
and yearly thereafter.
MAIN OUTCOME MEASURES: Breast cancer number and characteristics, and
frequency of abnormal mammograms by estrogen plus progestin exposure.
RESULTS: In intent-to-treat analyses, estrogen plus progestin increased
total (245 vs 185 cases; hazard ratio [HR], 1.24; weighted P<.001)
and invasive (199 vs 150 cases; HR, 1.24; weighted P =.003) breast cancers
compared with placebo. The invasive breast cancers diagnosed in the
estrogen plus progestin group were similar in histology and grade but
were larger (mean [SD], 1.7 cm [1.1] vs 1.5 cm [0.9], respectively;
P =.04) and were at more advanced stage (regional/metastatic 25.4% vs
16.0%, respectively; P =.04) compared with those diagnosed in the placebo
group. After 1 year, the percentage of women with abnormal mammograms
was substantially greater in the estrogen plus progestin group (716
[9.4%] of 7656) compared with placebo group (398 [5.4%] of 7310; P<.001),
a pattern which continued for the study duration.
CONCLUSIONS: Relatively short-term combined estrogen plus progestin
use increases incident breast cancers, which are diagnosed at a more
advanced stage compared with placebo use, and also substantially increases
the percentage of women with abnormal mammograms. These results suggest
estrogen plus progestin may stimulate breast cancer growth and hinder
breast cancer diagnosis. |
|
Noncardiovascular Disease Outcomes During 6.8 Years of Hormone Therapy:
Heart and Estrogen/Progestin Replacement Study Follow-up (HERS II).
Hulley S, Furberg C, Barrett-Connor E, Cauley J, Grady D, Haskell
W, Knopp R, Lowery M, Satterfield S, Schrott H, Vittinghoff E, Hunninghake
D.
University of California, San Francisco, San Francisco, CA 94143-0560.
|
JAMA 2002 Jul 3;288(1):58-64 Abstract quote
CONTEXT: The Heart and Estrogen/progestin Replacement Study (HERS)
was a randomized trial of estrogen plus progestin therapy after menopause.
OBJECTIVE: To examine the effect of long-term postmenopausal hormone
therapy on common noncardiovascular disease outcomes.
DESIGN AND SETTING: Randomized, blinded, placebo-controlled trial of
4.1 years' duration (HERS) and subsequent open-label observational follow-up
for 2.7 years (HERS II), carried out between 1993 and 2000 in outpatient
and community settings at 20 US clinical centers.
PARTICIPANTS: A total of 2763 postmenopausal women with coronary disease
and average age of 67 years at enrollment in HERS; 2321 women (93% of
those surviving) consented to follow-up in HERS II.
INTERVENTION: Participants were randomly assigned to receive 0.625
mg/d of conjugated estrogens plus 2.5 mg of medroxyprogesterone acetate
(n = 1380) or placebo (n = 1383) during HERS; open-label hormone therapy
was prescribed at personal physicians' discretion during HERS II. The
proportions with at least 80% adherence to hormones declined from 81%
(year 1) to 45% (year 6) in the hormone group and increased from 0%
(year 1) to 8% (year 6) in the placebo group.
MAIN OUTCOME MEASURES: Thromboembolic events, biliary tract surgery,
cancer, fracture, and total mortality.
RESULTS: Comparing women assigned to hormone therapy with those assigned
to placebo, the unadjusted intention-to-treat relative hazard (RH) for
venous thromboembolism declined from 2.66 (95% confidence interval [CI],
1.41-5.04) during HERS to 1.40 (95% CI, 0.64-3.05) during HERS II (P
for time trend =.08); it was 2.08 overall for the 6.8 years (95% CI,
1.28-3.40), and 3 of the 73 women with thromboembolism died within 30
days due to pulmonary embolism. The overall RH for biliary tract surgery
was 1.48 (95% CI, 1.12-1.95); for any cancer, 1.19 (95% CI, 0.95-1.50);
and for any fracture, 1.04 (95% CI, 0.87-1.25). There were 261 deaths
among those assigned to hormone therapy and 239 among those assigned
to placebo (RH, 1.10; 95% CI, 0.92-1.31). Adjusted and as-treated analyses
did not alter our conclusions.
CONCLUSIONS: Treatment for 6.8 years with estrogen plus progestin in
older women with coronary disease increased the rates of venous thromboembolism
and biliary tract surgery. Trends in other disease outcomes were not
favorable and should be assessed in larger trials and in broader populations. |
|
Risks and benefits of estrogen plus progestin in healthy postmenopausal
women: principal results From the Women's Health Initiative randomized
controlled trial.
Writing Group for the Women's Health Initiative Investigators.
|
JAMA 2002 Jul 17;288(3):321-33 Abstract quote
CONTEXT: Despite decades of accumulated observational evidence, the
balance of risks and benefits for hormone use in healthy postmenopausal
women remains uncertain.
OBJECTIVE: To assess the major health benefits and risks of the most
commonly used combined hormone preparation in the United States.
DESIGN: Estrogen plus progestin component of the Women's Health Initiative,
a randomized controlled primary prevention trial (planned duration,
8.5 years) in which 16608 postmenopausal women aged 50-79 years with
an intact uterus at baseline were recruited by 40 US clinical centers
in 1993-1998.
INTERVENTIONS: Participants received conjugated equine estrogens, 0.625
mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506)
or placebo (n = 8102).
MAIN OUTCOMES MEASURES: The primary outcome was coronary heart disease
(CHD) (nonfatal myocardial infarction and CHD death), with invasive
breast cancer as the primary adverse outcome. A global index summarizing
the balance of risks and benefits included the 2 primary outcomes plus
stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer,
hip fracture, and death due to other causes.
RESULTS: On May 31, 2002, after a mean of 5.2 years of follow-up, the
data and safety monitoring board recommended stopping the trial of estrogen
plus progestin vs placebo because the test statistic for invasive breast
cancer exceeded the stopping boundary for this adverse effect and the
global index statistic supported risks exceeding benefits. This report
includes data on the major clinical outcomes through April 30, 2002.
Estimated hazard ratios (HRs) (nominal 95% confidence intervals [CIs])
were as follows: CHD, 1.29 (1.02-1.63) with 286 cases; breast cancer,
1.26 (1.00-1.59) with 290 cases; stroke, 1.41 (1.07-1.85) with 212 cases;
PE, 2.13 (1.39-3.25) with 101 cases; colorectal cancer, 0.63 (0.43-0.92)
with 112 cases; endometrial cancer, 0.83 (0.47-1.47) with 47 cases;
hip fracture, 0.66 (0.45-0.98) with 106 cases; and death due to other
causes, 0.92 (0.74-1.14) with 331 cases. Corresponding HRs (nominal
95% CIs) for composite outcomes were 1.22 (1.09-1.36) for total cardiovascular
disease (arterial and venous disease), 1.03 (0.90-1.17) for total cancer,
0.76 (0.69-0.85) for combined fractures, 0.98 (0.82-1.18) for total
mortality, and 1.15 (1.03-1.28) for the global index. Absolute excess
risks per 10 000 person-years attributable to estrogen plus progestin
were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive
breast cancers, while absolute risk reductions per 10 000 person-years
were 6 fewer colorectal cancers and 5 fewer hip fractures. The absolute
excess risk of events included in the global index was 19 per 10 000
person-years.
CONCLUSIONS: Overall health risks exceeded benefits from use of combined
estrogen plus progestin for an average 5.2-year follow-up among healthy
postmenopausal US women. All-cause mortality was not affected during
the trial. The risk-benefit profile found in this trial is not consistent
with the requirements for a viable intervention for primary prevention
of chronic diseases, and the results indicate that this regimen should
not be initiated or continued for primary prevention of CHD. |
| HORMONE REPLACEMENT THERAPY-CARDIOVASCULAR
DISEASE |
|
|
Cardiovascular Disease Outcomes During 6.8 Years of Hormone Therapy:
Heart and Estrogen/Progestin Replacement Study Follow-up (HERS II).
Grady D, Herrington D, Bittner V, Blumenthal R, Davidson M, Hlatky
M, Hsia J, Hulley S, Herd A, Khan S, Newby LK, Waters D, Vittinghoff
E, Wenger N.
University of California, San Francisco, 74 New Montgomery St, Suite
600, San Francisco, CA 94105.
|
JAMA 2002 Jul 3;288(1):49-57 Abstract quote
CONTEXT: The Heart and Estrogen/progestin Replacement Study (HERS)
found no overall reduction in risk of coronary heart disease (CHD) events
among postmenopausal women with CHD. However, in the hormone group,
findings did suggest a higher risk of CHD events during the first year,
and a decreased risk during years 3 to 5.
OBJECTIVE: To determine if the risk reduction observed in the later
years of HERS persisted and resulted in an overall reduced risk of CHD
events with additional years of follow-up.
DESIGN AND SETTING: Randomized, blinded, placebo-controlled trial of
4.1 years' duration (HERS) and subsequent unblinded follow-up for 2.7
years (HERS II) conducted at outpatient and community settings at 20
US clinical centers.
PARTICIPANTS: A total of 2763 postmenopausal women with CHD and average
age of 67 years at enrollment in HERS; 2321 women (93% of those surviving)
consented to follow-up in HERS II.
INTERVENTION: Participants were randomly assigned to receive 0.625
mg/d of conjugated estrogens and 2.5 mg of medroxyprogesterone acetate
(n = 1380), or placebo (n = 1383) during HERS; open-label hormone therapy
was prescribed at personal physicians' discretion during HERS II. The
proportions with at least 80% adherence to hormones declined from 81%
(year 1) to 45% (year 6) in the hormone group, and increased from 0%
(year 1) to 8% (year 6) in the placebo group.
MAIN OUTCOME MEASURES: The primary outcome was nonfatal myocardial
infarction and CHD death. Secondary cardiovascular events were coronary
revascularization, hospitalization for unstable angina or congestive
heart failure, nonfatal ventricular arrhythmia, sudden death, stroke
or transient ischemic attack, and peripheral arterial disease.
RESULTS: There were no significant decreases in rates of primary CHD
events or secondary cardiovascular events among women assigned to the
hormone group compared with the placebo group in HERS, HERS II, or overall.
The unadjusted relative hazard (RH) for CHD events in HERS was 0.99
(95% confidence interval [CI], 0.81-1.22); HERS II, 1.00 (95% CI, 0.77-1.29);
and overall, 0.99 (0.84-1.17). The overall RHs were similar after adjustment
for potential confounders and differential use of statins between treatment
groups (RH, 0.97; 95% CI, 0.82-1.14), and in analyses restricted to
women who were adherent to randomized treatment assignment (RH, 0.96;
95% CI, 0.77-1.19).
CONCLUSIONS: Lower rates of CHD events among women in the hormone group
in the final years of HERS did not persist during additional years of
follow-up. After 6.8 years, hormone therapy did not reduce risk of cardiovascular
events in women with CHD. Postmenopausal hormone therapy should not
be used to reduce risk for CHD events in women with CHD.
|
|
Effects of hormone replacement therapy and antioxidant vitamin supplements
on coronary atherosclerosis in postmenopausal women: a randomized controlled
trial.
Waters DD, Alderman EL, Hsia J, Howard BV, Cobb FR, Rogers
WJ, Ouyang P, Thompson P, Tardif JC, Higginson L, Bittner V, Steffes
M, Gordon DJ, Proschan M, Younes N, Verter JI.
Division of Cardiology, Room 5G1, San Francisco General Hospital,
1001 Potrero Ave, San Francisco, CA 94110. |
JAMA 2002 Nov 20;288(19):2432-40 Abstract quote
CONTEXT: Hormone replacement therapy (HRT) and antioxidant vitamins
are widely used for secondary prevention in postmenopausal women with
coronary disease, but no clinical trials have demonstrated benefit to
support their use.
OBJECTIVE: To determine whether HRT or antioxidant vitamin supplements,
alone or in combination, influence the progression of coronary artery
disease in postmenopausal women, as measured by serial quantitative
coronary angiography.
DESIGN, SETTING, AND PATIENTS: The Women's Angiographic Vitamin and
Estrogen (WAVE) Trial, a randomized, double-blind trial of 423 postmenopausal
women with at least one 15% to 75% coronary stenosis at baseline coronary
angiography. The trial was conducted from July 1997 to January 2002
in 7 clinical centers in the United States and Canada.
INTERVENTIONS: Patients were randomly assigned in a 2 x 2 factorial
design to receive either 0.625 mg/d of conjugated equine estrogen (plus
2.5 mg/d of medroxyprogesterone acetate for women who had not had a
hysterectomy), or matching placebo, and 400 IU of vitamin E twice daily
plus 500 mg of vitamin C twice daily, or placebo.
MAIN OUTCOME MEASURE: Annualized mean (SD) change in minimum lumen
diameter (MLD) from baseline to concluding angiogram of all qualifying
coronary lesions averaged for each patient. Patients with intercurrent
death or myocardial infarction (MI) were imputed the worst rank of angiographic
outcome.
RESULTS: The mean (SD) interval between angiograms was 2.8 (0.9) years.
Coronary progression, measured in mean (SD) change, worsened with HRT
by 0.047 (0.15) mm/y and by 0.024 (0.15) mm/y with HRT placebo (P =.17);
and for antioxidant vitamins by 0.044 (0.15) mm/y and with vitamin placebo
by 0.028 (0.15) mm/y (P =.32). When patients with intercurrent death
or MI were included, the primary outcome showed an increased risk for
women in the active HRT group (P =.045), and suggested an increased
risk in the active vitamin group (P =.09). Fourteen patients died in
the HRT group and 8 in the HRT placebo group (hazard ratio [HR], 1.8;
95% confidence interval [CI], 0.75-4.3), and 16 in the vitamin group
and 6 in the vitamin placebo group (HR, 2.8; 95% CI, 1.1-7.2). Death,
nonfatal MI, or stroke occurred in 26 HRT patients vs 15 HRT controls
(HR, 1.9; 95% CI, 0.97-3.6) and in 26 vitamin patients and 18 vitamin
controls (HR, 1.5; 95% CI, 0.80-2.9). There was no interaction between
the 2 treatment interventions.
CONCLUSION: In postmenopausal women with coronary disease, neither
HRT nor antioxidant vitamin supplements provide cardiovascular benefit.
Instead, a potential for harm was suggested with each treatment. |
| HORMONE REPLACEMENT THERAPY-DEMENTIA |
|
Effect of Estrogen Plus Progestin on Global Cognitive Function in Postmenopausal
Women: The Women's Health Initiative Memory Study: A Randomized Controlled
Trial.
Rapp SR, Espeland MA, Shumaker SA, Henderson VW, Brunner RL,
Manson JE, Gass ML, Stefanick ML, Lane DS, Hays J, Johnson KC, Coker
LH, Dailey M, Bowen D.
Departments of Psychiatry and Behavioral Medicine, Wake Forest
University School of Medicine, Winston-Salem, NC.
|
JAMA 2003 May 28;289(20):2663-72 Abstract quote
CONTEXT: Observational studies have suggested that postmenopausal hormone
treatment may improve cognitive function, but data from randomized clinical
trials have been sparse and inconclusive. The Women's Health Initiative
Memory Study (WHIMS) is an ancillary study of the Women's Health Initiative
(WHI) hormone therapy trials. On July 8, 2002, the estrogen plus progestin
therapy in the WHI trial was discontinued because of certain increased
health risks for women.
OBJECTIVE: To determine whether estrogen plus progestin therapy protects
global cognitive function in older postmenopausal women.
DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled
clinical trial, WHIMS is an ancillary study of geographically diverse,
community-dwelling women aged 65 years or older from 39 of 40 clinical
centers within the WHI estrogen plus progestin trial that started in
June 1995. Of 4894 eligible postmenopausal women aged 65 years or older
and free of probable dementia at baseline, 4532 (92.6%) were enrolled
in the estrogen plus progestin component of WHIMS. A total of 4381 participants
(96.7%) provided at least 1 valid cognitive function score between June
1995 and July 8, 2002.
INTERVENTIONS: Participants received either 1 daily tablet containing
0.625 mg of conjugated equine estrogen with 2.5 mg of medroxyprogesterone
acetate (n = 2145) or matching placebo (n = 2236).
MAIN OUTCOME MEASURE: Global cognitive function measured annually with
the Modified Mini-Mental State Examination.
RESULTS: The Modified Mini-Mental State Examination mean total scores
in both groups increased slightly over time (mean follow-up of 4.2 years).
Women in the estrogen plus progestin group had smaller average increases
in total scores compared with women receiving placebo (P =.03), but
these differences were not clinically important. Removing women by censoring
them after adjudicated dementia, mild cognitive impairment, or stroke,
and nonadherence to study protocol, did not alter the findings. Prior
hormone therapy use and duration of prior use did not affect the interpretation
of the results, nor did timing of prior hormone therapy initiation with
respect to the final menstrual period. More women in the estrogen plus
progestin group had a substantial and clinically important decline (>/=2
SDs) in Modified Mini-Mental State Examination total score (6.7%) compared
with the placebo group (4.8%) (P =.008).
CONCLUSIONS: Among postmenopausal women aged 65 years or older, estrogen
plus progestin did not improve cognitive function when compared with
placebo. While most women receiving estrogen plus progestin did not
experience clinically relevant adverse effects on cognition compared
with placebo, a small increased risk of clinically meaningful cognitive
decline occurred in the estrogen plus progestin group. |
Estrogen Plus Progestin and the Incidence of Dementia and Mild Cognitive
Impairment in Postmenopausal Women: The Women's Health Initiative Memory
Study: A Randomized Controlled Trial.
Shumaker SA, Legault C, Thal L, Wallace RB, Ockene JK, Hendrix
SL, Jones BN 3rd, Assaf AR, Jackson RD, Morley Kotchen J, Wassertheil-Smoller
S, Wactawski-Wende J.
Department of Public Health Sciences, Wake Forest University
Health Sciences, Winston-Salem, NC.
|
JAMA 2003 May 28;289(20):2651-62 Abstract quote
CONTEXT: Postmenopausal women have a greater risk than men of developing
Alzheimer disease, but studies of the effects of estrogen therapy on
Alzheimer disease have been inconsistent. On July 8, 2002, the study
drugs, estrogen plus progestin, in the Women's Health Initiative (WHI)
trial were discontinued because of certain increased health risks in
women receiving combined hormone therapy.
OBJECTIVE: To evaluate the effect of estrogen plus progestin on the
incidence of dementia and mild cognitive impairment compared with placebo.
DESIGN, SETTING, AND PARTICIPANTS: The Women's Health Initiative Memory
Study (WHIMS), a randomized, double-blind, placebo-controlled clinical
trial, began enrolling participants from the Women's Health Initiative
(WHI) estrogen plus progestin trial in May 1996. Of the 4894 eligible
participants of the WHI study, 4532 (92.6%) postmenopausal women free
of probable dementia, aged 65 years or older, and recruited from 39
of 40 WHI clinical centers were enrolled in the WHIMS.
INTERVENTION: Participants received either 1 daily tablet of 0.625 mg
of conjugated equine estrogen plus 2.5 mg of medroxyprogesterone acetate
(n = 2229), or a matching placebo (n = 2303).
MAIN OUTCOME MEASURES: Incidence of probable dementia (primary outcome)
and mild cognitive impairment (secondary outcome) were identified through
a structured clinical assessment.
RESULTS: The mean (SD) time between the date of randomization into WHI
and the last Modified Mini-Mental State Examination (3MSE) for all WHIMS
participants was 4.05 (1.19) years. Overall, 61 women were diagnosed
with probable dementia, 40 (66%) in the estrogen plus progestin group
compared with 21 (34%) in the placebo group. The hazard ratio (HR) for
probable dementia was 2.05 (95% confidence interval [CI], 1.21-3.48;
45 vs 22 per 10 000 person-years; P =.01). This increased risk would
result in an additional 23 cases of dementia per 10 000 women per year.
Alzheimer disease was the most common classification of dementia in
both study groups. Treatment effects on mild cognitive impairment did
not differ between groups (HR, 1.07; 95% CI, 0.74-1.55; 63 vs 59 cases
per 10 000 person-years; P =.72).
CONCLUSIONS: Estrogen plus progestin therapy increased the risk for
probable dementia in postmenopausal women aged 65 years or older. In
addition, estrogen plus progestin therapy did not prevent mild cognitive
impairment in these women. These findings, coupled with previously reported
WHI data, support the conclusion that the risks of estrogen plus progestin
outweigh the benefits.
|
Estrogen Plus Progestin and the Incidence of Dementia and Mild Cognitive
Impairment in Postmenopausal Women: The Women's Health Initiative Memory
Study: A Randomized Controlled Trial.
Shumaker SA, Legault C, Thal L, Wallace RB, Ockene JK, Hendrix
SL, Jones BN 3rd, Assaf AR, Jackson RD, Morley Kotchen J, Wassertheil-Smoller
S, Wactawski-Wende J.
Department of Public Health Sciences, Wake Forest University
Health Sciences, Winston-Salem, NC. |
JAMA 2003 May 28;289(20):2651-62 Abstract quote
CONTEXT: Postmenopausal women have a greater risk than men of developing
Alzheimer disease, but studies of the effects of estrogen therapy on
Alzheimer disease have been inconsistent. On July 8, 2002, the study
drugs, estrogen plus progestin, in the Women's Health Initiative (WHI)
trial were discontinued because of certain increased health risks in
women receiving combined hormone therapy.
OBJECTIVE: To evaluate the effect of estrogen plus progestin on the
incidence of dementia and mild cognitive impairment compared with placebo.
DESIGN, SETTING, AND PARTICIPANTS: The Women's Health Initiative Memory
Study (WHIMS), a randomized, double-blind, placebo-controlled clinical
trial, began enrolling participants from the Women's Health Initiative
(WHI) estrogen plus progestin trial in May 1996. Of the 4894 eligible
participants of the WHI study, 4532 (92.6%) postmenopausal women free
of probable dementia, aged 65 years or older, and recruited from 39
of 40 WHI clinical centers were enrolled in the WHIMS.
INTERVENTION: Participants received either 1 daily tablet of 0.625 mg
of conjugated equine estrogen plus 2.5 mg of medroxyprogesterone acetate
(n = 2229), or a matching placebo (n = 2303).
MAIN OUTCOME MEASURES: Incidence of probable dementia (primary outcome)
and mild cognitive impairment (secondary outcome) were identified through
a structured clinical assessment. RESULTS: The mean (SD) time between
the date of randomization into WHI and the last Modified Mini-Mental
State Examination (3MSE) for all WHIMS participants was 4.05 (1.19)
years. Overall, 61 women were diagnosed with probable dementia, 40 (66%)
in the estrogen plus progestin group compared with 21 (34%) in the placebo
group. The hazard ratio (HR) for probable dementia was 2.05 (95% confidence
interval [CI], 1.21-3.48; 45 vs 22 per 10 000 person-years; P =.01).
This increased risk would result in an additional 23 cases of dementia
per 10 000 women per year. Alzheimer disease was the most common classification
of dementia in both study groups. Treatment effects on mild cognitive
impairment did not differ between groups (HR, 1.07; 95% CI, 0.74-1.55;
63 vs 59 cases per 10 000 person-years; P =.72).
CONCLUSIONS: Estrogen plus progestin therapy increased the risk for
probable dementia in postmenopausal women aged 65 years or older. In
addition, estrogen plus progestin therapy did not prevent mild cognitive
impairment in these women. These findings, coupled with previously reported
WHI data, support the conclusion that the risks of estrogen plus progestin
outweigh the benefits.
|
Hormone replacement therapy and incidence of Alzheimer disease in older
women: the cache county study.
Zandi PP, Carlson MC, Plassman BL, Welsh-Bohmer KA, Mayer LS,
Steffens DC, Breitner JC.
GRECC (S-182), VA Puget Sound Health Care System, 1660 S Columbian
Way, Seattle, WA 98108. |
JAMA 2002 Nov 6;288(17):2123-9 Abstract quote
CONTEXT: Previous studies have shown a sex-specific increased risk
of Alzheimer disease (AD) in women older than 80 years. Basic neuroscience
findings suggest that hormone replacement therapy (HRT) could reduce
a woman's risk of AD. Epidemiologic findings on AD and HRT are mixed.
OBJECTIVE: To examine the relationship between use of HRT and risk
of AD among elderly women.
DESIGN, SETTING, AND PARTICIPANTS: Prospective study of incident dementia
among 1357 men (mean age, 73.2 years) and 1889 women (mean age, 74.5
years) residing in a single county in Utah. Participants were first
assessed in 1995-1997, with follow-up conducted in 1998-2000. History
of women's current and former use of HRT, as well as of calcium and
multivitamin supplements, was ascertained at the initial contact.
MAIN OUTCOME MEASURE: Diagnosis of incident AD.
RESULTS: Thirty-five men (2.6%) and 88 women (4.7%) developed AD between
the initial interview and time of the follow-up (3 years). Incidence
among women increased after age 80 years and exceeded the risk among
men of similar age (adjusted hazard ratio [HR], 2.11; 95% confidence
interval [CI], 1.22-3.86). Women who used HRT had a reduced risk of
AD (26 cases among 1066 women) compared with non-HRT users (58 cases
among 800 women) (adjusted HR, 0.59; 95% CI, 0.36-0.96). Risk varied
with duration of HRT use, so that a woman's sex-specific increase in
risk disappeared entirely with more than 10 years of treatment (7 cases
among 427 women). Adjusted HRs were 0.41 (95% CI, 0.17-0.86) for HRT
users compared with nonusers and 0.77 (95% CI, 0.31-1.67) compared with
men. No similar effect was seen with calcium or multivitamin use. Almost
all of the HRT-related reduction in incidence reflected former use of
HRT (9 cases among 490 women; adjusted HR, 0.33 [95% CI, 0.15-0.65]).
There was no effect with current HRT use (17 cases among 576 women;
adjusted HR, 1.08 [95% CI, 0.59-1.91]) unless duration of treatment
exceeded 10 years (6 cases among 344 women; adjusted HR, 0.55 [95% CI,
0.21-1.23]).
CONCLUSIONS: Prior HRT use is associated with reduced risk of AD, but
there is no apparent benefit with current HRT use unless such use has
exceeded 10 years. |
| HORMONE REPLACEMENT THERAPY-OVARIAN CANCER |
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Menopausal hormone replacement therapy and risk of ovarian cancer.
Lacey JV Jr, Mink PJ, Lubin JH, Sherman ME, Troisi R, Hartge P,
Schatzkin A, Schairer C.
National Cancer Institute, Division of Cancer Epidemiology and Genetics,
6120 Executive Blvd, MSC 7234, Rockville, MD 20852. |
JAMA 2002 Jul 17;288(3):334-41 Abstract quote
CONTEXT: The association between menopausal hormone replacement therapy
and ovarian cancer is unclear.
OBJECTIVE: To determine whether hormone replacement therapy using estrogen
only, estrogen-progestin only, or both estrogen only and estrogen-progestin
increases ovarian cancer risk.
DESIGN: A 1979-1998 cohort study of former participants in the Breast
Cancer Detection Demonstration Project, a nationwide breast cancer screening
program.
SETTING: Twenty-nine US clinical centers.
PARTICIPANTS: A total of 44 241 postmenopausal women (mean age at start
of follow-up, 56.6 years).
MAIN OUTCOME MEASURE: Incident ovarian cancer.
RESULTS: We identified 329 women who developed ovarian cancer during
follow-up. In time-dependent analyses adjusted for age, menopause type,
and oral contraceptive use, ever use of estrogen only was significantly
associated with ovarian cancer (rate ratio [RR], 1.6; 95% confidence
interval [CI], 1.2-2.0). Increasing duration of estrogen-only use was
significantly associated with ovarian cancer: RRs for 10 to 19 years
and 20 or more years were 1.8 (95% CI, 1.1-3.0) and 3.2 (95% CI, 1.7-5.7),
respectively (P value for trend <.001), and we observed a 7% (95%
CI, 2%-13%) increase in RR per year of use. We observed significantly
elevated RRs with increasing duration of estrogen-only use across all
strata of other ovarian cancer risk factors, including women with hysterectomy.
The RR for estrogen-progestin use after prior estrogen-only use was
1.5 (95% CI, 0.91-2.4), but the RR for estrogen-progestin-only use was
1.1 (95% CI, 0.64-1.7). The RRs for less than 2 years and 2 or more
years of estrogen-progestin-only use were 1.6 (95% CI, 0.78-3.3) and
0.80 (95% CI, 0.35-1.8), respectively, and there was no evidence of
a duration response (P value for trend =.30).
CONCLUSION: Women who used estrogen-only replacement therapy, particularly
for 10 or more years, were at significantly increased risk of ovarian
cancer in this study. Women who used short-term estrogen-progestin-only
replacement therapy were not at increased risk, but risk associated
with short-term and longer-term estrogen-progestin replacement therapy
warrants further investigation. |
