WHI Trial of Estrogen plus Progestin: Reviewers Comments

1
WHI Trial of Estrogen plus Progestin Reviewers
Comments

• Endocrinologic and Metabolic Drugs
  Advisory Committee Meeting
• Rockville, Maryland - 7 October 2003
• Bruce V. Stadel, MD, MPH
• Division of Metabolic and Endocrine Drug Products

Center for Drug Evaluation and Research
2
(No Transcript)
3
(No Transcript)
4
IMS Health, National Prescription Audit Plus,
1995 July 2003, extracted August 2003.

5
WHI Trial of Estrogen plus
Progestin Invasive Breast Cancer by
Prior Menopausal Hormone Use

N diagnosed/N randomized
()
Prior
Use Estrogen plus progestin
58/2225 (2.61) Placebo
29/2079
(1.39) Difference
1.22 (95
confidence interval)
(0.38 to 2.08)
No
Prior Use Estrogen plus progestin
141/6277 (2.25) Placebo
121/6020
(2.01) Difference
0.24 (95
confidence interval)
(0.28 to 0.75) Derived from Chlebowski et
al. JAMA. 20032893243-3253


6

Relative Risk of Breast Cancer
for Users of Hormone Replacement Therapy
in the Million Women Study
From Million Women Study
Collaborators. Lancet. 2003362419-427.
7

Relative Risk of Breast Cancer
for Users of Hormone Replacement Therapy
in the Million Women Study
From Million Women Study
Collaborators. Lancet. 2003362419-427.
8
Major Path of Estrogen Production in
Postmenopausal Women

• Androstenedione,
• mostly from the adrenal glands,
• is aromatized to estrone
• in adipose tissue

9
Can Measuring Endogenous Estrogens Predict
Response To Treatment? Osteoporosis 1.
Cummings SR, Browner WS, Bauer D, et al.
Endogenous hormones and the risk
of hip and vertebral fractures among older women.
N Engl J
Med. 1998339733-738.


Postmenopausal women with
undetectable serum estradiol concentrations


and high serum
concentrations of sex hormone globulin have an
increased
risk of hip and
vertebral fracture.


Breast Cancer

2. Endogenous
Hormones and Breast Cancer Collaborative Group.

Body mass index, serum sex hormones, and
breast cancer risk in
postmenopausal women. J Natl Cancer Inst.
2003951218-1226. The
results are compatible with the hypothesis that
the increase in breast
cancer risk with increasing BMI among
postmenopausal women is largely the
the
result of
the associated increase in estrogens,
particularly bioavailable estradiol.