Determinantes del consumo de tratamiento hormonal sustitutivo y asociación con la densidad mamográfica en las mujeres participantes en los programas de detección precoz de cáncer de mama en España

Abstract

Justification: Hormone replacement therapy (HRT) is the therapy indicated for the treatment or prevention of symptoms and conditions associated with the menopause, aiming to compensate the physiological loss of estrogen associated to this stage of women life. This therapy includes the administration of estrogen and / or progestogen in peri- and postmenopausal women, fundamentally. During the 80’s and until the end of 90’s, vasomotor symptoms associated with menopause were primarily treated with estrogen and progestogen. However, in 2002, the clinical trial results from The Women's Health Initiative (WHI) were published, evidencing a breast cancer risk associated with estrogen plus progestin consumption. The publication of the WHI study led to a decrease in consumption of HRT, both internationally and in our country. Also, in the last decade the interest has risen about the role of isoflavones as an alternative or complementary therapy to HRT in postmenopausal women, due to the weak estrogenic effect they posses, which may interfere with the action and metabolism of endogenous estrogens. The prevalence of use of isoflavones in our country is virtually unknown. HRT consumption is an important risk factor for breast cancer. Different studies have recently proposed the use of mammographic density as “intermediate phenotype” or biological early effect variable. This is justified by the variation in mammographic density after the exposure or cessation of exposure to well known risk factors, including HRT, especially in postmenopausal women. The role of isoflavones on breast cancer risk and its association with mammographic density generates more controversy. Experimental and epidemiological studies provide contradictory results. Therefore, this study aims, first, to determine the prevalence of HRT and isoflavones in postmenopausal Spanish women and the factors associated with such use, and secondly, to explore the relationship between the use of these therapies and mammographic density, evaluating both the type of HRT consumed, and the duration of their consumption. Methods. To answer these questions we used the women included in the DDM -Spain study (Determinants of Mammography Density in Spain). It is a population-based study whose objective was to quantify the prevalence of high mammographic density and investigate the determinants of this marker of breast cancer risk in women participating in breast cancer screening programs in Spain. The population basis of the study are women with age between 45 and 68 years attending to the screening centers of the regions of Aragon, Balearic Islands, Castilla- Leon, Catalonia, Galicia, Navarra and Valencia. The sample size included 2.754 postmenopausal women, which answered a structured questionnaire. Multinomial regression models have been developed for the calculation of the determinants of HRT and isoflavones consumption, considering as the dependent variable a three-categories variable for consumers: women non-users of HRT, women ever users of HRT and women ever users of isoflavones. These models were adjusted for women age and screening center. To assess the possible association between the use of HRT and isoflavones and high mammographic density, we used ordinal regression models. In addition, taking into account the possible heterogeneity of mammograms of each center, mixed models were used, considering the screening center as a random effect term. Main results. The prevalence of HRT consumption in studied women, both present and past, has been 12.0%, while the prevalence of consumption at the time the survey was conducted was 2.3%. Regarding isoflavones, the prevalence throughout the women’s life reach 3.7%, but only 1.7% was consuming this treatment at the time of the survey. The mean duration of HRT use was 5.5 years, higher than isoflavone intake (3.1 years). The most consumed type of HRT at the time of the survey was tibolone, followed by estrogens. The estrogen-progesterone combined therapy and progesterone preparations have obtained lower use rates. The factors associated with a greater likelihood of HRT consumption were: surgical menopause, oral contraceptive use, a higher educational level and years passed since menopause. By contrast, the rurality, greater BMI and higher number of children are significantly associated with a lower likelihood of consumption. Regarding isoflavones, only age and number of elapsed years since menopause are postulated were inversely related with consumption. In relation to mammographic density, the results did not show an increased risk of higher density in women with HRT use, past or present. Also, there were not significant differences in the type of preparation consumed or the duration of it. However, women who reported having consumed isoflavones in the past showed an excess risk of increased breast density compared to non-consumers women. As a result, it would be important to confirm these associations in other studies with bigger sample sizes, due to the low prevalence of use of this type of treatment in our population, and to expand the research in the field of alternative therapies aimed at the treatment of symptoms associated with menopause.