Hormoontherapie na de menopauze kan risico op kanker verhogen of verkleinen. Oestrogeen verhoogt. Oestrogeen plus Progesteen verkleint.

23 juni 2024: Bron: ASCO 2024

Het kankerrisico verschilt per type hormoontherapie dat postmenopauzale vrouwen gebruiken om de klachten van de overgang te beperken. Hormoontherapie met alleen oestrogeen kan het risico op eierstokkanker verhogen, terwijl therapie met oestrogeen plus progestageen het risico op endometriumkanker kan verlagen.

Rowan Chlebowski, M.D., Ph.D., van het Lundquist Institute in Torrance, Californië, en collega’s evalueerden gegevens uit twee gerandomiseerde onderzoeken die deel uitmaakten van het Women’s Health Initiative. Aan de twee onderzoeken namen 27.347 postmenopauzale vrouwen deel, in de leeftijd van 50 tot 79 jaar, die niet eerder borst- of invasieve kanker hadden gehad.
Vrouwen die een hysterectomie hadden ondergaan, werden willekeurig toegewezen aan alleen geconjugeerd paardenoestrogeen (CEE) of placebo, en vrouwen die nog een baarmoeder hadden, werden willekeurig toegewezen aan CEE plus medroxyprogesteronacetaat (MPA) of placebo.

De onderzoekers ontdekten dat na een follow-up van 20 jaar alleen CEE de incidentie van eierstokkanker (hazard ratio , 2,04) en de sterfte aan eierstokkanker significant verhoogde (HR, 2,79). Het gebruik van CEE plus MPA verhoogde de incidentie of mortaliteit van eierstokkanker echter niet in vergelijking met placebo. CEE plus MPA verlaagden de incidentie van endometriumkanker significant (HR, 0,72), maar hadden geen invloed op de sterfte aan endometriumkanker.

Het abstract van deze 2 studies is in te zien op ASCO 2024:

Menopausal hormone therapy and ovarian and endometrial cancers: Long-term follow-up of the Women’s Health Initiative randomized trials.

Authors

Rowan T. Chlebowski, Aaron K. Aragaki, Kathy Pan, Reina Haque, Thomas E Rohan, Mihae Song, Jean Wactawski-Wende, Dorothy Lane, Holly Harris, Howard D. Strickler, Andrew Kaunitz, Carolyn D. Runowicz

Organizations

The Lundquist Research Institute, Torrance, CA, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, Kaiser Permanente Southern California, Downey, CA, Kaiser Permanente Southern California, Pasadena, CA, Albert Einstein College of Medicine, New York, NY, City of Hope National Medical Center, Duarte, CA, University of Buffalo Department of Social and Preventive Medicine, Buffalo, NY, Department of Family, Population and Preventive Medicine, Renaissance School of Medicine, Stony Brook, NY, Fred Hutchinson Cancer Research Center, Seattle, WA, Albert Einsten College of Medicine, Bronx, NY, Department of Obstetrics & Gynecology, University of Florida College of Medicine Jacksonville, Jacksonville, FL, Florida International University Herbert Wertheim College of Medicine, Miami, FL

Abstract Disclosures

Research Funding

U.S. National Institutes of Health

National Cancer Institute

Background:

After decades of use,menopausal hormone therapy influence on ovarian and endometrial cancer remains unsettled. Therefore, we assessed the long-term influence of conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA) and CEE-alone use on ovarian and endometrial cancer incidence and mortality in long-term follow-up of the Women’s Health Initiative randomized, placebo-controlled clinical trials.

Methods:

Long-term follow-up of two placebo-controlled randomized clinical trials that recruited 27,347 postmenopausal women aged 50-79 years without prior breast cancer or invasive cancer within 10 years (and no baseline endometrial pathology in combined hormone trial participants) from 40 US centers from 1993-1998. In 16,608 women with a uterus, 8,506 were randomized to daily 0.625 mg/d of CEE plus 2.5 mg/d of MPA and 8,102, placebo. In 10,739 women with prior hysterectomy, 5,310 were randomized to daily 0.625 mg/d of CEE-alone and 5,429, placebo. Intervention was stopped for cause before the planned 8.5-year intervention after 5.6 years (CEE plus MPA) and after 7.2 years (CEE-alone). Cancers were verified by central pathology report review. Mortality findings were enhanced by serial National Death Index (NDI) queries. The primary study outcomes were ovarian cancer and endometrial cancer incidence and related mortality.

Results:

After 20-year follow-up, with mortality information for > 98%; in the initial WHI report on CEE-alone influence on ovarian cancer, CEE-alone, versus placebo, significantly increased ovarian cancer incidence (35 cases [0.041% annualized rate] vs 17 [0.020%]; hazard ratio , 2.04; 95% CI 1.14-3.65; P = 0.01) and ovarian cancer mortality (HR 2.79 95% CI 1.30-5.99, P = 0.006). KM-estimates and cumulative hazard ratios indicate a persistent CEE-alone adverse effect on ovarian cancer incidence that emerged after 12-years follow-up and did not diminish (P = 0.006). In contrast, use of CEE plus MPA, versus placebo, did not increase ovarian cancer incidence (75 cases [0.051%] vs 63 [0.045%]; HR, 1.14; 95% CI, 0.82-1.59; P = 0.44) or ovarian cancer mortality (HR 1.21 95% CI 0.84-1.74). CEE plus MPA did significantly lower endometrial cancer incidence (106 cases [0.073%] vs 140 [0.10%]; HR, 0.72; 95% CI, 0.56-0.92; P = 0.01), without statistically significant influence on endometrial mortality (HR 0.58 95% CI 0.29-1.16)Conclusions:In randomized, placebo-controlled, clinical trial settings, CEE-alone, in women with prior hysterectomy, significantly increased ovarian cancer incidence and increased ovarian cancer mortality while CEE plus MPA, in women with a uterus, in contrast to most observational studies, did not. However, CEE plus MPA reduced endometrial cancer incidence. These findings inform decisions regarding menopausal hormone therapy use. Clinical trial information: NCT00000611.