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Progestagen component in combined hormone replacement therapy in postmenopausal women and breast cancer risk: a debated clinical issue.
Gynecol Endocrinol. 2009 Dec; 25(12):807-15.GE

Abstract

The relevance of the progestagen component in combined hormone replacement therapy (HRT) for breast cancer risk has been long debated. In vitro studies have shown that progestins exert both genomic transcriptional and non-genomic effects that can enhance the proliferation, invasiveness and spread of breast cancer cells. According to a novel hypothesis, progestins can still activate cancer stem cells in patients with pre-existing, clinically undetected breast cancer. However, some experimental and clinical data suggest that different progestins may have a different impact on the pathophysiology of malignant breast cells. In vitro studies on estrogen receptor (ER)+ breast cancer cells have shown that the addition of medroxyprogesterone acetate (MPA) to estradiol (E(2)) produces a significantly higher increase of the mRNA levels and activities of estrogen-activating enzymes aromatase, 17beta hydroxysteroid dehydrogenase type-1 and sulfatase when compared with progesterone plus E(2). In randomised trial performed on ovariectomised adult female monkeys, oral E(2) plus MPA have resulted in a significantly greater proliferation of breast lobular and ductal epithelium when compared with placebo, whereas E(2) plus micronised progesterone have not. In the same experimental model, oral E(2) plus MPA have been found to induce the expression of genes encoding epidermal growth factor receptor (EGFR) ligands and downstream targets, whereas E(2) alone or E(2) plus micronised progesterone had no or modest effects on EGFR-related genes. In last years, some clinical studies on HRT users have shown that androgenic progestin- or MPA-based formulations are associated with an increased breast cancer incidence, whereas micronised progesterone- or dydrogesterone-based formulations are not. Further basic and clinical investigations on this topic are strongly warranted to elucidate whether the choice of the progestagen component in combined HRT could be of clinical relevance as for breast cancer risk.

Authors+Show Affiliations

Department of Procreative Medicine, Division of Gynecology and Obstetrics, University of Pisa, Pisa, Italy. a.gadducci@obgyn.med.unipi.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

19906000

Citation

Gadducci, Angiolo, et al. "Progestagen Component in Combined Hormone Replacement Therapy in Postmenopausal Women and Breast Cancer Risk: a Debated Clinical Issue." Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology, vol. 25, no. 12, 2009, pp. 807-15.
Gadducci A, Biglia N, Cosio S, et al. Progestagen component in combined hormone replacement therapy in postmenopausal women and breast cancer risk: a debated clinical issue. Gynecol Endocrinol. 2009;25(12):807-15.
Gadducci, A., Biglia, N., Cosio, S., Sismondi, P., & Genazzani, A. R. (2009). Progestagen component in combined hormone replacement therapy in postmenopausal women and breast cancer risk: a debated clinical issue. Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology, 25(12), 807-15. https://doi.org/10.3109/09513590903056878
Gadducci A, et al. Progestagen Component in Combined Hormone Replacement Therapy in Postmenopausal Women and Breast Cancer Risk: a Debated Clinical Issue. Gynecol Endocrinol. 2009;25(12):807-15. PubMed PMID: 19906000.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Progestagen component in combined hormone replacement therapy in postmenopausal women and breast cancer risk: a debated clinical issue. AU - Gadducci,Angiolo, AU - Biglia,Nicoletta, AU - Cosio,Stefania, AU - Sismondi,Piero, AU - Genazzani,Andrea Riccardo, PY - 2009/11/13/entrez PY - 2009/11/13/pubmed PY - 2010/1/27/medline SP - 807 EP - 15 JF - Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology JO - Gynecol Endocrinol VL - 25 IS - 12 N2 - The relevance of the progestagen component in combined hormone replacement therapy (HRT) for breast cancer risk has been long debated. In vitro studies have shown that progestins exert both genomic transcriptional and non-genomic effects that can enhance the proliferation, invasiveness and spread of breast cancer cells. According to a novel hypothesis, progestins can still activate cancer stem cells in patients with pre-existing, clinically undetected breast cancer. However, some experimental and clinical data suggest that different progestins may have a different impact on the pathophysiology of malignant breast cells. In vitro studies on estrogen receptor (ER)+ breast cancer cells have shown that the addition of medroxyprogesterone acetate (MPA) to estradiol (E(2)) produces a significantly higher increase of the mRNA levels and activities of estrogen-activating enzymes aromatase, 17beta hydroxysteroid dehydrogenase type-1 and sulfatase when compared with progesterone plus E(2). In randomised trial performed on ovariectomised adult female monkeys, oral E(2) plus MPA have resulted in a significantly greater proliferation of breast lobular and ductal epithelium when compared with placebo, whereas E(2) plus micronised progesterone have not. In the same experimental model, oral E(2) plus MPA have been found to induce the expression of genes encoding epidermal growth factor receptor (EGFR) ligands and downstream targets, whereas E(2) alone or E(2) plus micronised progesterone had no or modest effects on EGFR-related genes. In last years, some clinical studies on HRT users have shown that androgenic progestin- or MPA-based formulations are associated with an increased breast cancer incidence, whereas micronised progesterone- or dydrogesterone-based formulations are not. Further basic and clinical investigations on this topic are strongly warranted to elucidate whether the choice of the progestagen component in combined HRT could be of clinical relevance as for breast cancer risk. SN - 1473-0766 UR - https://www.unboundmedicine.com/medline/citation/19906000/Progestagen_component_in_combined_hormone_replacement_therapy_in_postmenopausal_women_and_breast_cancer_risk:_a_debated_clinical_issue_ L2 - https://www.tandfonline.com/doi/full/10.3109/09513590903056878 DB - PRIME DP - Unbound Medicine ER -