Incidence of cervical cytological abnormalities with aging in the women's health initiative: a randomized controlled trial.
OBJECTIVE
To estimate the incidence of cytological abnormalities and cervical cancer and to determine the effect of oral estrogen and progestin on cervical cytology among postmenopausal women participating in a multi-institution clinical trial.


METHODS
The study was a longitudinal analysis of a prospective cohort of 16,608 postmenopausal women (aged 50-79 years) participating in the Women's Health Initiative (WHI) clinical trial of estrogen plus progestin. Eligible participants had a cervical smear within 1 year before randomization and at 3- and 6-year follow-ups. Outcomes measured were low-grade and high-grade squamous intraepithelial lesions (LSIL, HSIL) and cervical cancer at follow-up years 3 and 6.


RESULTS
Of 15,733 eligible participants with a uterus, 7,663 were assigned to placebo and 8,070 to estrogen plus progestin. At baseline, 318 women (2%) had low-grade abnormalities on cervical cytology. The annual incidence rate of any new cytological abnormality in the estrogen plus progestin group was significantly higher than that in the placebo group (hazard ratio 1.4, 95% confidence interval [CI] 1.2-1.6). Independent risk factors for HSIL and cervical cancer over a 6-year follow-up (after stratifying for baseline cytologic abnormalities) included sexual activity in the past year while not being married or living as married (hazard ratio 3.5, 95% CI 1.5-8.3). Risk factors did not include age or use of estrogen plus progestin.


CONCLUSIONS
Use of estrogen plus progestin was associated with increased incidence of any cytologic abnormality, although it had no impact on the incidence of HSIL or cervical cancer. Sexually active older women who are not married or living as married may benefit from continued cervical cancer screening.


BACKGROUND
Clinicaltrials.gov, www.clinicaltrials.gov, NCT00000611.
Yasmeen
Shagufta
S
Department of Obstetrics/Gynecology and Internal Medicine, University of California, Davis, 95817, USA. syasmeen@ucdavis.edu
Romano
Patrick S
PS
Pettinger
Mary
M
Johnson
Susan R
SR
Hubbell
F Allan
FA
Lane
Dorothy S
DS
Hendrix
Susan L
SL
D000368:Aged; D000375:Aging; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage; D005260:Female; D006293:Health Promotion; D006299:Health Services for the Aged; D006801:Humans; D015994:Incidence; D008137:Longitudinal Studies; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage; D008875:Middle Aged; D017698:Postmenopause; D016016:Proportional Hazards Models; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology; D014626:Vaginal Smears / Q000706:statistics & numerical data; D014932:Women's Health Services; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology
D004966:Estrogens, Conjugated (USP); D017258:Medroxyprogesterone Acetate