Effects of tibolone and continuous combined hormone therapy on mammographic breast density and breast histochemical markers in postmenopausal women

Valdivia, I; Campodónico, I; Tapia, Augusto; Capetillo, M; Espinoza, Arturo; Lavín, Pablo

doi:10.1016/j.fertnstert.2003.07.041

Cited by 75 publications

(51 citation statements)

References 28 publications

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“…1). This proliferative response of sequential conjugated equine estrogens-MPA is similar to that of conventional continuous combined treatment found in earlier studies (12,15,21,22) whereas the natural E 2 -P therapy did not increase breast cell proliferation significantly in conformity with previous findings (23). Increased proliferation during HT must be regarded as an unwanted potentially hazardous side effect whereas increased apoptosis reasonably is beneficial.…”

supporting

confidence: 89%

Effects of percutaneous estradiol–oral progesterone versus oral conjugated equine estrogens–medroxyprogesterone acetate on breast cell proliferation and bcl-2 protein in healthy women

Murkes¹,

Conner²,

Leifland³

et al. 2011

Fertility and Sterility

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Effects of percutaneous estradiol-oral progesterone versus oral conjugated equine estrogens-medroxyprogesterone acetate on breast cell proliferation and bcl-2 protein in healthy womenIn a prospective, randomized clinical study 77 women were assigned randomly to receive sequential hormone therapy with either conventional oral conjugated equine estrogens (0.625 mg) with the addition on 14 of the 28 days of oral medroxyprogesterone acetate (5 mg) or natural E 2 gel (1.5 mg) with oral micronized P (200 mg) on 14 of the 28 days of each cycle. Because oral conjugated equine estrogens-medroxyprogesterone acetate induced a highly significant increase in breast cell proliferation in contrast to percutaneous E 2 -oral P with a difference between therapies approaching significance, the former therapy has a marked impact on the breast whereas natural percutaneous E 2 -oral micronized P has not. (Fertil Steril Ò 2011;95:1188-91. Ó2011 by American Society for Reproductive Medicine.)Key Words: Percutaneous estradiol, micronized progesterone, HT, proliferation, bcl-2 protein, normal breast tissue Postmenopausal hormone therapy (HT) has been associated with an increased risk for breast cancer. The risk with combined estrogen-progestogen therapy is greater than with estrogen alone (1-6). Hormone therapy is not a uniform concept, and various preparations, doses, and regimens of HT may have different effects (7). Although estrogen is a known mitogen in the breast, the effects of added progestogens may vary considerably (8-15), but proliferative responses are seen within 2 months (9-11). Synthetic progestogens may differ from natural P. In the French E3N cohort, women taking estrogen in combination with micronized P were found to have no increase in breast cancer risk in contrast to women taking estrogen in combination with synthetic progestogens (16,17).In this study we used core needle biopsy to evaluate breast cell proliferation in healthy postmenopausal women during two different types of sequential HTs: oral conjugated estrogens plus synthetic progestogen versus percutaneous E 2 plus natural oral micronized P. A prospective randomized clinical study was performed at the Karolinska University Hospital, Stockholm, Sweden, between May 2006 and March 2008. Apparently healthy women, aged 44 to 66 years, postmenopausal for at least 12 months, nonsmokers, with normal mammogram results, and with a body mass index of 18 to 30 kg/m 2 , were recruited. Follicle-stimulating hormone levels at screening were >25 IU/L, and E 2 levels <90 pmol/L. The washout period for previous HT users was 3 months.Exclusion criteria were any breast disease, previous breast surgery, hepatic dysfunction, active gallbladder disease, or history of thromboembolic disease. Medication with sexual steroids, barbiturates, carbamazepines, phenytoin, glucocorticoids, rifampicin, cimetidine, diltiazem, erythromycin, ketoconazole, verapamil, and quinidine was not permitted.

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supporting

confidence: 89%

Effects of percutaneous estradiol–oral progesterone versus oral conjugated equine estrogens–medroxyprogesterone acetate on breast cell proliferation and bcl-2 protein in healthy women

Murkes¹,

Conner²,

Leifland³

et al. 2011

Fertility and Sterility

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“…Mammographic breast density is strongly related to breast cancer risk (31)(32)(33)(34)(35)(36)(37)(38)(39)(40) and has been proposed as an intermediate marker in studies of potential approaches for the prevention of breast cancer (41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52). Mammographic breast density seems to reflect extent of epithelial and nonepithelial cells in the breast (53) as well as epithelial and/or stromal proliferation (54) and this may explain, at least in part, the relation of breast density with breast cancer risk.…”

Section: Introductionmentioning

confidence: 99%

Vitamin D and Calcium Intakes from Food or Supplements and Mammographic Breast Density

Bérubé

Diorio

Mâsse

et al. 2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: A better understanding of factors that affect breast density, one of the strongest breast cancer risk indicators, may provide important clues about breast cancer etiology and prevention. This study evaluates the association of vitamin D and calcium, from food and/or supplements, to breast density in premenopausal and postmenopausal women separately. Methods: A total of 777 premenopausal and 783 postmenopausal women recruited at two radiology clinics in Quebec City, Canada, in 2001 to 2002, completed a food frequency questionnaire to assess vitamin D and calcium. Breast density from screening mammograms was assessed using a computer-assisted method. Associations between vitamin D or calcium and breast density were evaluated using linear regression models. Adjusted means in breast density were assessed according to the combined daily intakes of the two nutrients using generalized linear models.

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“…40,41,49 There were 5 RCTs that assessed change in BD with tibolone intervention. [48][49][50][51][52] Ages of participants ranged from 41 to 70 years, and the sample size ranged from 37 to 177 (n = 665). Tibolone administration was 2.5 mg/d, and duration of administration was 1 year.…”

Section: Resultsmentioning

confidence: 99%

Relationship Between Breast Density and Selective Estrogen-Receptor Modulators, Aromatase Inhibitors, Physical Activity, and Diet

et al. 2016

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Background. Lower breast density (BD) is associated with lower risk of breast cancer and may serve as a biomarker for the efficacy of chemopreventive strategies. This review explores parameters that are thought to be associated with lower BD. We conducted a systematic review of articles published to date using the PRISMA strategy. Articles that assessed change in BD with estrogen-receptor modulators (tamoxifene [TAM], raloxifene [RLX], and tibolone) and aromatase inhibitors (AIs), as well as cross-sectional and longitudinal studies (LSs) that assessed association between BD and physical activity (PA) or diet were reviewed. Results. Ten studies assessed change in BD with TAM; all reported TAM-mediated BD decreases. Change in BD with RLX was assessed by 11 studies; 3 reported a reduction in BD. Effect of tibolone was assessed by 5 RCTs; only 1 reported change in BD. AI-mediated BD reduction was reported by 3 out of 10 studies. The association between PA and BD was assessed by 21 studies; 4 reported an inverse association. The relationship between diet and BD was assessed in 34 studies. All studies on calcium and vitamin D as well as vegetable intake reported an inverse association with BD in premenopausal women. Two RCTs demonstrated BD reduction with a low-fat, high-carbohydrate intervention. Conclusion. TAM induces BD reduction; however, the effect of RLX, tibolone, and AIs on BD is unclear. Although data on association between diet and BD in adulthood are contradictory, intake of vegetables, vitamin D, and calcium appear to be associated with lower BD in premenopausal women.

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Effects of tibolone and continuous combined hormone therapy on mammographic breast density and breast histochemical markers in postmenopausal women

Cited by 75 publications

References 28 publications

Effects of percutaneous estradiol–oral progesterone versus oral conjugated equine estrogens–medroxyprogesterone acetate on breast cell proliferation and bcl-2 protein in healthy women

Effects of percutaneous estradiol–oral progesterone versus oral conjugated equine estrogens–medroxyprogesterone acetate on breast cell proliferation and bcl-2 protein in healthy women

Vitamin D and Calcium Intakes from Food or Supplements and Mammographic Breast Density

Relationship Between Breast Density and Selective Estrogen-Receptor Modulators, Aromatase Inhibitors, Physical Activity, and Diet

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