0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
ARTICLE |

Effects of Hormone Replacement Therapy on Endometrial Histology in Postmenopausal Women:  The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial

Howard L. Judd, MD; Irma Mebane-Sims, PhD; Claudine Legault, PhD; Carol Wasilauskas, MS; Susan Johnson, MD; Maria Merino, MD; Elizabeth Barrett-Connor, MD; Jose Trabal, MD; Valery T. Miller, MD; Vanessa Barnabei, MD; Ginny Levin, MPH.; Trudy Bush, PhD; David Foster, MD; Howard Zacur, MD; J. Donald Woodruff, MD; Marcia Stefanick, PhD; Peter D. Wood, DSc, PhD; Allison Akana, PA; W. Leroy Heinrichs, MD; Katherine O'Hanlan, MD; Richard P. Buyalos, MD; Gail Greendale, MD; Kathy Lozano, RNP; Mary Lou Carrion-Petersen, RN; Carmella Cavero, RN; Robert Langer, MD; Helmut G. Schrott, MD; Jo Ann Benda, MD; Charles deProsse, MD; Deborah Fedderson, RN; Susan R. Johnson, MD; Jose Trabal, MD, MPH; Carl J. Pauerstein, MD; Mohammad M. Ahmad, MD, PhD; Herbert P. Brown, MD; Robert S. Schenken, MD; Mercedes Rodriguez-Sifuentes, RN; Philip T. Valente, MD; Mark Espeland, PhD; H. Bradley Wells, PhD; Kathy Lane; Carol Wasilauskas, MS.; Irma L. Mebane-Sims, PhD; Joseph Kelaghan, MD; Joan McGowan, PhD; Judith Fradkin, MD; Sheryl Sherman, PhD; Robert Scully, MD
JAMA. 1996;275(5):370-375. doi:10.1001/jama.1996.03530290040035.
Text Size: A A A
Published online

Objective.  —To report the histological findings of the endometrium of postmenopausal women who were randomized to receive placebo, estrogen only, or one of three estrogen plus progestin (E+P) regimens in the Postmenopausal Estrogen/ Progestin Interventions (PEPI) Trial.

Design.  —A 3-year multicenter, randomized, double-masked, placebo-controlled trial.

Participants  —A total of 596 postmenopausal women aged 45 through 64 years without contraindication to hormone therapy.

Intervention.  —Participants were randomized and stratified in equal numbers to one of the following treatments in 28-day cycles: placebo, 0.625 mg/d of conjugated equine estrogens (CEE), 0.625 mg/d of CEE plus 10 mg/d of medroxyprogesterone acetate (MPA) for the first 12 days, 0.625 mg/d of CEE plus 2.5 mg/d of MPA, or 0.625 mg/d of CEE plus 200 mg/d of micronized progesterone (MP) for the first 12 days.

Outcome Measure.  —Histology of endometrium collected at baseline, annual, or unscheduled visits by biopsy, curettage, or hysterectomy.

Analysis.  —Intention to treat.

Results.  —During follow-up women assigned to estrogen alone were more likely to develop simple (cystic), complex (adenomatous), or atypical hyperplasia than those given placebo (27.7% vs 0.8%, 22.7% vs 0.8%, and 11.8% vs 0%, respectively) for the same types of hyperplasia (P<.001). Participants administered one of the three E+P regimens had similar rates of hyperplasia as those given placebo (P=.16). The occurrence of hyperplasia was distributed evenly across the 3 years of the trial. Women taking estrogens alone also had more unscheduled biopsies (66.4% vs 8.4%; P<.001) and curettages (17.6% vs 0.8%; P<.001) than women receiving placebo. The number of surgical procedures was similar for women receiving placebo and women receiving the E+P regimens (P=.38). Of the 45 women with complex (adenomatous) or atypical hyperplasia, study medications were discontinued in all, and the biopsy results of 34 (94%) of 36 women with hyperplasia reverted to normal with progestin therapy. The remainder had dilatation and curettage (n=2) or hysterectomy with (n=2) or without (n=6) prior medical therapy, or refused further biopsies (n=1). One woman developed adenocarcinoma of the endometrium while receiving placebo.

Conclusions.  —At a dosage of 0.625 mg, the daily administration of CEE enhanced the development of endometrial hyperplasia. Combining CEE with cyclic or continuous MPA or cyclic MP protected the endometrium from hyperplastic changes associated with estrogen-only therapy.(JAMA. 1996;275:370-375)

Topics

Sign in

Create a free personal account to sign up for alerts, share articles, and more.

Purchase Options

• Buy this article
• Subscribe to the journal

Figures

Tables

References

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Sign in

Create a free personal account to sign up for alerts, share articles, and more.

Purchase Options

• Buy this article
• Subscribe to the journal

Related Content

Customize your page view by dragging & repositioning the boxes below.

Jobs
brightcove.createExperiences();