Breast cancer risk during hormone therapy: Experimental versus clinical data
Department of Gynecological Endocrinology, University of Beijing, Beijing, China.Minerva endocrinologica (Impact Factor: 1.46). 03/2012; 37(1):59-74.
Evidence is increasing suggesting that adding progestogens to estrogens can increase the risk of breast cancer. However, our experimental data as a result of scientific collaboration between university of Tuebingen, Germany, and university of Beijing, China, comparing all available progestogens used in hormone therapy and hormonal contraception present high evidence that there may be differences regarding breast cancer risk. Especially of concern may be to differentiate between primary and secondary risk i.e. between the effect of on benign and malignant breast epithelial cells suggesting differences in primary risk and risk in patients after breast cancer. Of importance also is that in contrast to natural progesterone the apocrine impact of stromal growth factors and also certain cell components of breast epithelial cells can strongly increase proliferation rates of some (but not all. synthetic progestogens which can lead to clinical cancer before (in contrast to estrogen-only therapy. carcinoprotective mechanisms can work. Regarding clinical data, epidemiological studies and especially the Women's Health Initiative, so far the only prospective placebo-controlled study, demonstrate an increased risk under combined estrogen/progestogen-, but not under estrogen-only therapy. However, up to now the clinical studies cannot discriminate between the various progestogens mostly due to too small patient numbers in the subgroups, and in most studies either medroxyprogesterone acetate or norethisterone have been used. However, there is evidence that the natural progesterone and dydrogesterone, possibly also the transdermal usage of synthetic progestogens, may have less risks, but this must be proven in further clinical trials.
- Climacteric 08/2013; 16 Suppl 1(S1):3-4. DOI:10.3109/13697137.2013.816915 · 2.26 Impact Factor
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ABSTRACT: The population-based case-control study CECILE investigated the impact of various menopausal hormone therapy (MHT) products on breast cancer (BC) risk in 1,555 postmenopausal women . The case group (n = 739) included incident cases of in situ (!) or invasive BC in postmenopausal women. The control group (n = 816) included women from the general population within predefined quotas by age and socio-economic status (SES). While quotas by age were applied to obtain similar distributions by age among controls and among cases, quotas by SES in control women were applied to reflect the distribution by SES of women in the general population in the study area. Data of participants were obtained by a structured questionnaire during in-person interviews, and from pathology reports if applicable, respectively. Women were divided into current and past MHT user. MHTs were classified in estrogen-only therapy (ET), estrogen combined with progestin therapy (EPT) and tibolone. EPT was subdivided in three subtypes according to the progestogen constituent: natural micronized progesterone, progesterone derivatives, and testosterone derivatives. In comparison to never MHT users, any current or past MHT use (ET, EPT, tibolone) was not associated with an increased BC risk. However, in subanalysis BC risk was significantly increased for current use of EPT for 4 or more years (n = 73 cases and n = 56 controls, adjusted OR 1.55; 95 % CI 1.02-2.36). Within the group of current EPT users for 4 or more years, 14 cases had used estrogens combined with micronized progesterone (n = 17 controls), and 55 a combination with a synthetic progestogen (n = 34 controls), respectively. Compared to never MHT use, current use of EPT containing a synthetic progestogen for 4 or more years was associated with a significantly increased BC risk (adjusted OR 2.07; 95 % CI 1.26-3.39), but EPT containing micronized progesterone was not (adjusted OR 0.79; 95 % CI 0.37-1.71). 73 % of current MHT users started treatment within the first year of onset of menopause. Early EPT (n = 52 cases and n = 38 controls, adjusted OR 1.65; 95 % CI 1.02-2.69), but not early ET, starters had a significantly higher BC risk compared to never MHT users. In contrast, MHT initiation beyond 1 year after menopause was not associated with an increased BC risk. The authors concluded that: (1) ET and EPT containing natural progesterone did not increase BC risk whereas, (2) BC risk was increased in users of tibolone or EPT containing a synthetic progestogen, respectively, and that (3) MHT use early after onset of menopause was associated with an increased BC risk as compared to women who delay MHT beyond 1 or more years.Archives of Gynecology and Obstetrics 05/2014; 290(2). DOI:10.1007/s00404-014-3270-0 · 1.36 Impact Factor
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ABSTRACT: Objectives: The aim of this study was to evaluate the in vitro skin permeation and in vivo transdermal absorption of natural progesterone (Prog) from alcoholic gel-based transdermal formulations containing Prog dissolved stably at a concentration of 3%. Methods: 3% Prog dissolved gel formulations were prepared containing with water, ethanol, 1,3-butylene glycol, carboxyvinylpolymer, diisopropanolamine, polyoxyethylene (2) oleylether and benzyl alcohol. The gel formulations added different hydrophilic surfactants and isopropyl myristate or propylene glycol dicaprylate (PGDC) as oily solvents were applied in vitro permeation study through excised rat skin on unocclusive condition. The gel formulations added polyoxyethylene (20) oleylether (Oleth-20) as hydrophilic surfactant and PGDC were applied in vivo single- and repeated-dose transdermal absorption study of rat on unocclusive condition. Results: The results of evaluation of the gel formulations by an in vitro skin permeation study revealed a high flux of Prog from the formulation containing Oleth-20 and Oleth-20 with PGDC. The results of single and repeated in vivo transdermal absorption studies confirmed that good plasma levels of Prog were achieved and maintained by Oleth-20 and PGDC containing gel formulation. Conclusions: The Oleth-20 and PGDC containing ethanolic gel formulation seemed to have the ability to maintain a high activity of Prog and high diffusivity or solubility of Prog in the epidermis on the practical formulation application.Drug Development and Industrial Pharmacy 07/2014; 41(6):1-4. DOI:10.3109/03639045.2014.925915 · 2.10 Impact Factor
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