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Lancet. 2015 May 9;385(9980):1835-42. doi: 10.1016/S0140-6736(14)61687-1. Epub 2015 Feb 13.

Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies.

Collaborators (149)

Gapstur SM, Patel AV, Banks E, Dal Maso L, Talamini R, Chetrit A, Hirsh-Yechezkel G, Lubin F, Sadetzki S, Beral V, Bull D, Cairns B, Crossley B, Gaitskell K, Goodill A, Green J, Hermon C, Key T, Moser K, Reeves G, Sitas F, Collins R, Peto R, Gonzalez CA, Lee N, Marchbanks P, Ory HW, Peterson HB, Wingo PA, Martin N, Silpisornkosol S, Theetranont C, Boosiri B, Chutivongse S, Jimakorn P, Virutamasen P, Wongsrichanalai C, Goodman MT, Lidegaard O, Kjaer SK, Morch LS, Kjaer SK, Tjonneland A, Byers T, Rohan T, Mosgaard B, Vessey M, Yeates D, Freudenheim JL, Titus LJ, Chang-Claude J, Kaaks R, Anderson KE, Lazovich D, Robien K, Hampton J, Newcomb PA, Rossing MA, Thomas DB, Weiss NS, Lokkegaard E, Riboli E, Clavel-Chapelon F, Cramer D, Hankinson SE, Tamimi RM, Tworoger SS, Franceschi S, La Vecchia C, Negri E, Adami HO, Magnusson C, Riman T, Weiderpass E, Wolk A, Schouten LJ, van den Brandt PA, Chantarakul N, Koetsawang S, Rachawat D, Palli D, Black A, Brinton LA, Freedman DM, Hartge P, Hsing AW, Lacey Jnr JV, Lissowska J, Hoover RN, Schairer C, Babb C, Urban M, Graff -Iversen S, Selmer R, Bain CJ, Green AC, Purdie DM, Siskind V, Webb PM, Moysich K, McCann SE, Hannaford P, Kay C, Binns CW, Lee AH, Zhang M, Ness RB, Nasca P, Coogan PF, Palmer JR, Rosenberg L, Whittemore A, Katsouyanni K, Trichopoulou A, Trichopoulos D, Tzonou A, Dabancens A, Martinez L, Molina R, Salas O, Lurie G, Carney ME, Wilkens LR, Hartman L, Manjer J, Olsson H, Kumle M, Grisso JA, Morgan M, Wheeler JE, Edwards RP, Kelley JL, Modugno F, Onland-Moret NC, Peeters PH, Casagrande J, Pike MC, Wu AH, Canfell K, Miller AB, Gram IT, Lund E, McGowan L, Shu XO, Zheng W, Farley TM, Holck S, Meirik O, Risch HA.

Abstract

BACKGROUND:

Half the epidemiological studies with information about menopausal hormone therapy and ovarian cancer risk remain unpublished, and some retrospective studies could have been biased by selective participation or recall. We aimed to assess with minimal bias the effects of hormone therapy on ovarian cancer risk.

METHODS:

Individual participant datasets from 52 epidemiological studies were analysed centrally. The principal analyses involved the prospective studies (with last hormone therapy use extrapolated forwards for up to 4 years). Sensitivity analyses included the retrospective studies. Adjusted Poisson regressions yielded relative risks (RRs) versus never-use.

FINDINGS:

During prospective follow-up, 12 110 postmenopausal women, 55% (6601) of whom had used hormone therapy, developed ovarian cancer. Among women last recorded as current users, risk was increased even with <5 years of use (RR 1·43, 95% CI 1·31-1·56; p<0·0001). Combining current-or-recent use (any duration, but stopped <5 years before diagnosis) resulted in an RR of 1·37 (95% CI 1·29-1·46; p<0·0001); this risk was similar in European and American prospective studies and for oestrogen-only and oestrogen-progestagen preparations, but differed across the four main tumour types (heterogeneity p<0·0001), being definitely increased only for the two most common types, serous (RR 1·53, 95% CI 1·40-1·66; p<0·0001) and endometrioid (1·42, 1·20-1·67; p<0·0001). Risk declined the longer ago use had ceased, although about 10 years after stopping long-duration hormone therapy use there was still an excess of serous or endometrioid tumours (RR 1·25, 95% CI 1·07-1·46, p=0·005).

INTERPRETATION:

The increased risk may well be largely or wholly causal; if it is, women who use hormone therapy for 5 years from around age 50 years have about one extra ovarian cancer per 1000 users and, if its prognosis is typical, about one extra ovarian cancer death per 1700 users.

FUNDING:

Medical Research Council, Cancer Research UK.

PMID:
25684585
PMCID:
PMC4427760
DOI:
10.1016/S0140-6736(14)61687-1
[Indexed for MEDLINE]
Free PMC Article

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