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PubMed2004

Bone mineral density changes over two years in first-time users of depot medroxyprogesterone acetate.

OBJECTIVE: To compare longitudinal changes in bone mineral density (BMD) among first-time depot medroxyprogesterone acetate (DMPA) users to women using no hormonal contraception, and evaluate user characteristics associated with that BMD change. DESIGN: Prospective longitudinal study. SETTING: Healthy volunteers in an academic research environment. PATIENT(S): Women, aged 18 to 35, choosing DMPA for contraception (n = 178) and women using no hormonal contraception (n = 145). MAIN OUTCOME MEASURE(S): Hip and spine BMD measured, at three-month intervals for 24 months, by dual energy x-ray absorptiometry. RESULT(S): Mean hip BMD declined 2.8% (SE = 0.034) 12 months following DMPA initiation and 5.8% (SE = 0.096) after 24 months. Mean spine (L1-L3) BMD declined 3.5% (SE = 0.022) and 5.7% (SE = 0.034), respectively, after one and two years of DMPA use. Mean hip and spine BMD of control participants changed less than 0.9% over the same period. Among DMPA users, body mass index (BMI) change was inversely associated with BMD change at the hip, but not at the spine. Calcium intake, physical activity, and smoking did not influence BMD change in either group. CONCLUSION(S): Hip and spine BMD declined after one DMPA injection and this decline continued with each subsequent injection for 24 months. With the exception of increasing BMI among DMPA users, no user characteristics offered protection against DMPA-related BMD loss.

Absorptiometry, Photon↗
PubMed2006

Bone mineral density loss and recovery during 48 months in first-time users of depot medroxyprogesterone acetate.

OBJECTIVE: To compare changes in bone mineral density (BMD) during 48 months between first-time depot medroxyprogesterone acetate (MPA) users, during use and after discontinuation, to controls. DESIGN: Longitudinal study. SETTING: Academic community. PATIENT(S): Women 18-35 years, newly initiating depot MPA (n = 178) and controls (n = 145) not using hormonal contraception. MAIN OUTCOME MEASURE(S): The BMD of the hip and spine, measured at 3-month intervals, by dual energy roentgen absorptiometry. RESULTS: Hip and spine BMD declined during 48 months of depot MPA use by 7.7% +/- 0.11% (mean +/- SE) and 6.4% +/- 0.36%, respectively. The BMD of controls declined <or=1.6% +/- 0.30%. Hip and spine BMD loss slowed to <0.6% after 48 months of depot MPA use. After discontinuation, BMD increased from 0.3% to 2.0% per year depending on length of depot MPA use and bone site. The longest depot MPA users remained 4.7% and 2.9% lower than hip and spine baseline values, respectively, 18 months after discontinuation. CONCLUSION(S): Depot MPA-related BMD loss is substantial but occurs mostly during the first 2 years of DMPA use. Therefore, longer use may not substantially increase the risk of osteoporosis. The prolonged recovery time suggests the need to consider timing of use in relation to menopause or other factors that may impede bone remodeling.

Bone Density↗
PubMed2006

Mifepristone alters expression of endometrial steroid receptors and their cofactors in new users of medroxyprogesterone acetate.

OBJECTIVE: To evaluate the effect of mifepristone on the expression of endometrial steroid receptors and their co-factors in depot medroxyprogesterone acetate (DMPA) users. DESIGN: A prospective, randomized, placebo-controlled trial. SETTING: Reproductive research center. PATIENT(S): Fifty healthy women with regular menstrual cycle. INTERVENTION(S): One hundred fifty milligrams of DMPA were given every 3 months. Two pills (25 mg each) of placebo or mifepristone were administered every 14 days during the DMPA therapy. Four endometrial biopsy specimens were obtained from each patient. MAIN OUTCOME MEASURE(S): The expression of estrogen receptor subtypes alpha and beta (ERalpha and ERbeta), progesterone receptors A and B (PRAB and PRB), and androgen receptor messenger RNA and protein was detected by real-time polymerase chain reaction and immunohistochemistry, respectively. Steroid receptor coactivator 1 (SRC-1), silencing mediator for retinoid and thyroid-hormone receptors, and cell proliferation were evaluated by immunohistochemistry. RESULT(S): The expression of endometrial ERalpha, PRAB, PRB, and SRC-1 was increased significantly after 1 week of mifepristone, but the increase was no longer seen after 10 weeks. A positive correlation between endometrial ERalpha, PRAB, PRB, and SRC-1 production and proliferation was demonstrated. CONCLUSION(S): Short-term exposure of mifepristone in new starters of DMPA increases the expression of endometrial ERalpha, PRAB, PRB, and SRC-1 and promotes cell proliferation. Prolonged exposure to mifepristone does not alter the suppression of these receptors that are caused by DMPA and continues to result in endometrial atrophy.

Contraceptives, Oral, Synthetic↗
PubMed2004

Depot medroxyprogesterone acetate, oral contraceptives and bone mineral density in a cohort of adolescent girls.

PURPOSE: To conduct a longitudinal comparison of bone mineral density (BMD) in 370 adolescent girls, aged 12-18, who self-selected depot medroxyprogesterone acetate (DMPA) or an oral contraceptive (OC) containing 20 microg ethinyl estradiol/100 microg levonorgestrel with that in girls who received no hormonal treatment (control group). METHODS: Lumbar spine and femoral neck BMD measurements were obtained by dual energy x-ray absorptiometry at baseline and 12 months. Data were analyzed with repeated measures analysis of covariance methods. RESULTS: Over 12 months, lumbar spine BMD decreased in the DMPA group (n = 29), with a mean percent change of -1.4% (95% confidence interval [CI] -2.73, -0.10), and increased by a mean of 3.8% (95% CI 3.11, 4.57) in the control group [n = 107 (p < .001)]. The increase in mean percent change in lumbar spine BMD in the OC group (n = 79), 2.3% (95% CI 1.49, 3.18), was significantly smaller than in the control group (p = .03). Over 12 months, the mean percent change in femoral neck BMD was -2.2% (95% CI -3.95, -0.39) in the DMPA group, but increased 2.3% (95% CI 1.29, 3.27) in the control group (p < .001). The increase in mean percent change at the femoral neck in the OC group, 0.3% (95% CI -0.87, 1.41), was significantly lower than in the control group (p = .03). CONCLUSIONS: Our study contributes to an increasing body of knowledge indicating a negative impact of DMPA on bone health in young women. Additional findings suggest a potential adverse effect of an OC containing 20 microg ethinyl estradiol/100 microg levonorgestrel on bone health in adolescents.

Absorptiometry, Photon↗
PubMed2006

Depot medroxyprogesterone acetate and bone mineral density in adolescents--the Black Box Warning: a Position Paper of the Society for Adolescent Medicine.

The purpose of this Position Paper is to review the published Black Box Warning regarding depot medroxyprogesterone acetate (DMPA) and bone loss as it relates to adolescent girls. The scientific findings that prompted the Food and Drug Administration to issue the warning are reviewed and the following additional issues are considered: (1) likely low risk of fracture related to DMPA use, (2) evidence of at least partial recovery after discontinuation of the method, and (3) the need to balance the physical, social and economic cost of adolescent pregnancy versus the immediate and long-term impact of DMPA on bone. A list of clinical guidelines is included, the main recommendation of which is to continue prescription of DMPA, with counseling about the risks and benefits, in most of the adolescent population desiring to use this contraceptive method.

Adolescent↗
PubMed2005

Clinical, pathological and immunohistochemical study of feline mammary fibroepithelial hyperplasia following a single injection of depot medroxyprogesterone acetate.

Feline mammary fibroepithelial hyperplasia (FMFH) following a single injection of depot medroxyprogesterone acetate (MPA) was observed in eight intact young queens. The repository compound is marketed as a veterinary product by a local pharmaceutical company with an indication for contraception in cats. The drug was administered according to the recommended doses and injection frequencies. Serum hormone assays performed immediately before neutering and 3 weeks after neutering detected persistently high levels of progesterone suggesting that depot MPA was still exerting its influence. No corpora lutea were found in those cases ruling out ovaries as the main site of progesterone. Immunohistochemistry performed on the hyperplastic mammary glands detected progesterone receptors in the nuclei of ductal cells, and growth hormone (GH) and insulin-like growth factor-I (IGF-I) in the cytoplasm of ductal epithelium. Overdosing should be considered here as the animals received at least 10 mg/kg of depot MPA in a single injection. Progestin-induced local synthesis of GH and IGF-I in mammary epithelial cells is suggested as one of the pathogenic mechanisms involved in the development of FMFH.

Animals↗
PubMed2004

Bone mineral density in adolescent females using depot medroxyprogesterone acetate.

STUDY OBJECTIVE: To examine bone mineral density (BMD) on a semi-annual basis among control subjects and adolescent females receiving depot medroxyprogesterone acetate (DMPA) injection or oral contraceptives. DESIGN: Non-randomized prospective study. SETTING: Teenage pregnancy prevention intervention clinic. PARTICIPANTS: Adolescent females who were new users of DMPA injection (N=58, age 12-21) or the oral contraceptive pill (N=71, age 11-19) and normal menstruating girls (N=19, age 15-18). INTERVENTIONS: Baseline and 6-monthly measures of lumbar vertebral BMD using dual-energy X-ray absorptiometry over a 2-year period. MAIN OUTCOME MEASURES: comparison of percent change on BMD over time between DMPA users, pill users, and normal menstruating girls. RESULTS: There was no difference on group characteristics at baseline except for the ethnicity between the controls and the DMPA group. There was a statistically significant decrease in BMD between DMPA users and controls at 6 months (-3.02% change, P=0.014) 12 months (-3.38% change, P=0.001) 18 months (-4.81% change, P<0.001) and 24 months (-6.81% change, P=0.010). There was no statistical difference between pill users and controls. CONCLUSION: There is a relationship between DMPA use and a decrease in BMD compared to normal menstruating controls that seems to persist up to 24 months.

Absorptiometry, Photon↗
PubMed2004

Weight gain, adiposity, and eating behaviors among adolescent females on depot medroxyprogesterone acetate (DMPA).

OBJECTIVE: To identify risk factors for weight gain and explore body composition and eating behaviors among adolescent females initiating depot medroxyprogesterone acetate (DMPA). METHODS: A longitudinal study was conducted in 43 adolescent females beginning DMPA. Data collection at baseline, 3, and 6 months included structured interview; measurement of height, weight, and percent body fat; and assessment of dietary restraint, disinhibition, and appetite. RESULTS: Black and white subjects did not differ in baseline weight or body composition. At 6 months, black subjects had a 4.2% increase in weight (mean weight gain=2.9 kg; P=0.003) and a 12.5% increase in body fat (mean fat gain =2.5 kg; P<0.001). In contrast, white subjects had a 1.2% increase in weight (mean weight gain=0.9 kg; P=0.32) and a 1.2% increase in body fat (mean fat gain of 0.5 kg; P=0.54). Baseline weight (P<0.001), study visit (P=0.005), age (P=0.006), eating restraint (P=0.005), eating disinhibition (P<0.001), and other medications (P<0.001) were predictive of weight gain in black subjects. Only baseline weight (P<0.001) was predictive in white subjects. Higher baseline weight (adjusted odds ratio (AOR)=1.2, 95% confidence interval (CI)=1.1,1.3) was a risk factor for gaining >2.2 kg the first 3 months. Black race (AOR=7.8, 95% CI=1.5, 66.2) and younger age at menarche (AOR=0.6, 95% CI=0.3, 0.9) were risk factors for gaining >2.2 kg the second 3 months. Appetite decreased in the study sample reaching statistical significance in black subjects. CONCLUSIONS: Our data suggest that black and white adolescents differ in the quantity, timing, and predictors of weight gain on DMPA. DMPA-associated weight gain is paralleled by increases in total body fat, while appetite decreases on DMPA.

Adolescent↗
PubMed2004

Bone biochemical markers in adolescent girls using either depot medroxyprogesterone acetate or an oral contraceptive.

STUDY OBJECTIVE: To examine the relationship between biochemical markers of bone metabolism and hormonal contraception in adolescents. DESIGN: A prospective, observational design. SETTING: The study was conducted in four adolescent health clinics in a large metropolitan area. PARTICIPANTS: The study population comprised healthy, postmenarcheal adolescent girls aged 12-18 initiating either medroxyprogesterone acetate (n=53) or an oral contraceptive (OC) containing 20 mug ethinyl estradiol/100 mug levonorgestrel (n=165) and those using no hormonal contraception (n=152). INTERVENTIONS: None. MAIN OUTCOME MEASURES: Serum bone specific alkaline phosphatase (BSAP), urinary deoxypyridinoline (DPD), and bone mineral density (BMD) at baseline and 12 months. RESULTS: At 12 month follow-up, serum BSAP levels were significantly higher (P < 0.05) in the control group (40.4 U/L +/- 1.03 SE), than in the DMPA group (35.2 U/L +/- 1.05 SE) and the OC group (35.5 U/L +/- 1.03 SE). There was a trend in urinary DPD levels to be higher (P=0.08) in the control group (9.9 nmol/mmol Cr +/- 1.03 SE) than in the DMPA group (9.1 +/- 1.05 SE) and the OC group (8.9 +/- 1.03 SE). No relationship was found between the biochemical markers and BMD at the lumbar spine or the femoral neck. CONCLUSIONS: Over 12 months, there was evidence of increased bone formation and resorption in the control group when compared to that in the DMPA and OC groups. This finding may indicate a suppression of bone metabolism in girls using DMPA or an OC containing 20 mug ethinyl estradiol/100 mug levonorgestrel.

Adolescent↗
PubMed2004

Effects of celecoxib, medroxyprogesterone, and dietary intervention on systemic syndromes in patients with advanced lung adenocarcinoma: a pilot study.

Systemic syndromes characterized by a persistent activity of circulating mediators (cytokines) are frequently present with advanced cancer. We grouped under the general heading of "Systemic Immune-Metabolic Syndrome (SIMS)" a particular variety of distressing systemic syndrome characterized by dysregulation of the psycho-neuro-immune-endocrine homeostasis, with overlapping clinical manifestations. SIMS may include cachexia, anorexia, nausea, early satiety, fatigue, tumor fever, cognitive changes and superinfection. The aim of this study was to ameliorate some of the SIMS symptoms in a homogeneous group of lung adenocarcinoma patients using a multitargeted therapy. Fifteen patients with evidence of SIMS were studied. SIMS was defined as the presence of weight loss, anorexia, fatigue performance status>/=2 and acute-phase protein response. Patients received medroxyprogesterone (MPA) (500 mg twice daily), celecoxib (200 mg twice daily), plus oral food supplementation for 6 weeks. After treatment, 13 patients either had stable weight (+/- 1%) or had gained weight. There were significant differences in improvement of body-weight-change rate, nausea, early satiety, fatigue, appetite and performance status. Patients who had any kind of lung infection showed higher levels of IL-10 compared to non-infected patients (P=0.039). Our results suggest that patients with advanced lung adenocarcinoma, treated with MPA, celecoxib and dietary intervention, might have considerable improvement in certain SIMS outcomes. This multitargeted symptomatic approach deserves further study.

Adenocarcinoma↗
PubMed2005

A stability-indicating HPLC method for medroxyprogesterone acetate in bulk drug and injection formulation.

A stability-indicating HPLC assay method has been developed and validated for medroxyprogesterone acetate (MPA) in bulk drug and injectable suspension. An isocratic RP-HPLC was achieved on a Hichrom C(18) column (150 mm x 4.6mm i.d., 5 microm) utilizing a mobile phase of methanol 0.020 M acetate buffer pH 5 (65:35, v/v) and a photodiode array detector at 245 nm. The stress testing of MPA was carried out under acidic and alkaline hydrolysis, and oxidation conditions. MPA was well resolved from its degradation products, a main related substance (megestrol acetate) and two preservatives (methyl paraben and propyl paraben) with the resolution >or=2. The proposed method was validated for selectivity, linearity, accuracy, precision and solution stability. The method was found to be suitable for the quality control of MPA in bulk drug and injections as well as the stability-indicating studies.

Chemistry, Pharmaceutical↗
PubMed2006

Characterization of the stimulatory effect of medroxyprogesterone acetate and chlormadinone acetate on growth factor treated normal human breast epithelial cells.

OBJECTIVE: Evidence is increasing that adding progestogens to hormone replacement therapy may be more harmful than beneficial, however it is debatable whether all progestogens act equally on breast cells. Mitogenic growth factors from stromal breast tissue are important in growth-regulation of breast cells, and may modify responses to progestogens. We investigated the effect of two C-21 derivatives, medroxyprogesterone acetate (MPA) and chlormadinone acetate (CMA) on growth-factor treated normal breast epithelial cells and tried to explore the underlying mechanisms of proliferation. METHOD: MCF10A (human epithelial, estrogen- and progesterone-receptor negative normal breast cells) were incubated with MPA or CMA at 0.1 and 1 microM for 7 days with the growth factors (GFs) EGF, bFGF and IGF-I at 1pM. The same combinations, as well as growth factors alone, were also incubated with the proliferation inhibitors PD98059 and LY294002 at 1 microM for 4 days. Cell proliferation rate was measured by the ATP-assay. RESULTS: MPA 0.1 and 1 microM, and CMA 1 microM in combination with GFs both significantly increased cell proliferation rate, with MPA having the greatest effect. MPA- and CMA-induced proliferation of GF stimulated cells was blocked by both PD98059 (selective inhibitor of MAP kinases) and LY294002 (phosphatidylinositol 3-kinase inhibitor); GF stimulated cells could not be significantly reduced by any of the inhibitors used. CONCLUSION: MPA and CMA have a stimulatory effect on benign growth factor stimulated MCF10A cells, possibly via activation of MAP kinase and subsequent substrates and activation of PI3-kinase. GF induced proliferation appear to be mediated by pathways other than those investigated here. Growth factors and progestogens therefore have an additive, synergistic effect on cell proliferation, eliciting their effects via different pathways.

Breast↗
PubMed2003

Metabolism of medroxyprogesterone acetate (MPA) via CYP enzymes in vitro and effect of MPA on bleeding time in female rats in dependence on CYP activity in vivo.

Medroxyprogesterone acetate (MPA) is a drug commonly used in endocrine therapy for advanced breast cancer, although it is known to cause thrombosis as a serious side effect. Recently, we found that cytochrome P450 3A4 (CYP3A4) mainly catalyzed the metabolism of MPA via CYP in human liver microsomes. However, the metabolic products of MPA in humans and rats have not been elucidated. In addition, it is not clear whether thrombosis could be induced by MPA itself or by its metabolites. In this study, we determined the overall metabolism of MPA as the disappearance of the parent drug from an incubation mixture, and identified the enzymes catalyzing the metabolism of MPA via CYP in rats. Moreover, the effects of CYP-modulators on MPA-induced hypercoagulation in vivo were examined. Intrinsic clearance of MPA in rat liver microsomes was increased by treatment with CYP3A-inducers. The intrinsic clearance of MPA in liver microsomes of rats treated with various CYP-inducers showed a significant correlation with CYP3A activity, but not CYP1A activity, CYP2B activity or CYP2C contents. Among the eight recombinant rat CYPs studied, CYP3A1, CYP3A2 and CYP2A2 catalyzed the metabolism of MPA. However, since CYP3A2 and CYP2A2 are male-specific isoforms, CYP3A1 appears to be mainly involved in the metabolism of MPA in liver microsomes of female rats. In an in vivo study, pretreatment of female rats with SKF525A, an inhibitor of CYPs including CYP3A1, significantly (p < 0.05) enhanced MPA-induced hypercoagulation, whereas pretreatment with phenobarbital, an inducer of CYPs including CYP3A1, reduced it. These findings suggest that CYP-catalyzed metabolism of MPA is mainly catalyzed by CYP3A1 and that MPA-induced hypercoagulation is predominantly caused by MPA itself in female rats.

Animals↗
PubMed2004

Pharmacokinetics of estradiol valerate and medroxyprogesterone acetate in different age groups of postmenopausal women.

OBJECTIVES: To study whether ageing affects the pharmacokinetics of estradiol valerate (E2V) or medroxyprogesterone acetate (MPA) in postmenopausal women. METHODS: Forty-six postmenopausal women from two essentially similar pharmacokinetic studies were divided into three age categories: under 60 years (n = 15), between 60 and 65 years (n = 18) and over 65 years (n = 13). They all were treated for 12 days or 14 days with four galenically identical tablets containing combinations of 1 mg or 2 mg E2V and 2.5 mg or 5 mg MPA. The studies followed an open, randomised cross-over design with no washout between the periods. Serum estradiol and MPA concentrations were measured at steady state on study day 12 or 14 of each period. RESULTS: No statistically significant differences were observed in the peak concentration (Cmax), time to peak (t(max)), AUC or elimination half-life for estradiol or MPA between the different age groups. In spite of the lack of statistical significance the AUC was on an average 1.6-fold and Cmax 1.40-fold higher in the oldest group of women than in the youngest group and age was found significant as a continuous variable for AUC and Cmax for MPA but not for estradiol. CONCLUSIONS: The results suggest that there would be no significant changes in the pharmacokinetics of estradiol between women under 60 and over 65 years of age. However, a significant trend towards higher MPA concentrations and bioavailability was observed with increasing age. The results suggest that from the pharmacokinetic point of view the relationship between estradiol and MPA dose to be used in elderly could be different from that in younger postmenopausal women, while no pharmacokinetic reasons to use lower estradiol doses in the elderly were observed.

Age Factors↗
PubMed2005

Conjugated estrogen plus medroxyprogesterone does not impair blood rheological properties in hypertensive postmenopausal women.

OBJECTIVES: Hypertension and estrogens are both prothrombotic. We used the microchannel method to investigate whether hormone replacement therapy (HRT) with conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA) affects blood flow through the microchannels in hypertensive postmenopausal women being treated with antihypertensive drugs and in normotensive postmenopausal women. METHODS: Sixty-two consecutive postmenopausal women were randomly assigned to a hypertensive HRT group (n=16), hypertensive control group (n=15), normotensive HRT group (n=16) and normotensive control group (n=15). Each HRT group received CEE 0.625 mg plus MPA 2.5 mg daily orally for 12 months. Both hypertensive groups were being treated with antihypertensive drugs before the study. Microvascular blood flow was assessed on the basis of blood passage time, the time required for 100 microl of whole blood to pass through a cylinder, was determined before and 12 months after the start of HRT by the microchannel method (micro channel array flow analyzer). RESULTS: CEE plus MPA therapy did not change blood passage time in any of the groups. Microscopic observation showed that the whole blood passed smoothly through the microchannels in every group. CONCLUSIONS: CEE plus MPA therapy may not impair blood flow through the microchannels in hypertensive postmenopausal women receiving antihypertensive drugs or in normotensive postmenopausal women. However, administration of CEE plus MPA to postmenopausal women with hypertension warrants caution against the occurrence of thromboembolic events.

Aged↗
PubMed2004

Medroxyprogesterone acetate downregulates cytokine gene expression in mouse fibroblast cells.

Although medroxyprogesterone acetate (MPA) is used as an injectable contraceptive, in hormone replacement therapy (HRT) and in treatment of certain cancers, the steroid receptors and their target genes involved in the actions of MPA are not well understood. We show that MPA, like dexamethasone (dex), significantly represses tumour necrosis factor (TNF)-stimulated interleukin-6 (IL-6) protein production in mouse fibroblast (L929sA) cells. In addition, MPA repressed IL-6 and IL-8 promoter-reporter constructs at the transcriptional level, via interference with nuclear factor kappaB (NFkappaB) and activator protein-1 (AP-1). Furthermore, like dex, MPA does not affect NFkappaB DNA-binding activity. We also observed significant transactivation by MPA of a glucocorticoid response element (GRE)-driven promoter-reporter construct in both L929sA and COS-1 cells. The MPA-induced nuclear translocation of the glucocorticoid receptor (GR), as well as the antagonistic effects of RU486, strongly suggest that the actions of MPA in these cells are mediated at least in part via the GR.

Animals↗
PubMed2005

Estradiol and medroxyprogesterone acetate regulated genes in T47D breast cancer cells.

Many mammary tumors express estrogen receptors (ER) and progesterone receptors (PR), and there is increasing evidence that progestins influence gene expression of breast tumor cells. To analyse the impact of progestins on breast cancer cells, we compared (a) the expression of two cytokines, involved in tumor progression, and searched (b) for differentially regulated genes by a microarray, containing 2400 genes, on T47D breast cancer cells cultured for 6 days with 17beta-estradiol (E2) or E2+medroxyprogesterone acetate (E2+MPA). Lower amounts of PDGF and TNFalpha were found in culture supernatants of E2+MPA treated T47D cells. MPA addition induced a 2.8-3.5-fold increase of the mRNA expression of (a) tristetraprolin, which is involved in the posttranscriptional regulation of cytokine biosynthesis, and (b) zinc-alpha2-glycoprotein and Na, K-ATPase alpha1-subunit, which both resemble differentiation markers of breast epithelium. In contrast, the mRNA expression of lipocalin 2, which promotes matrixmetalloproteinase-9 activity, was decreased five-fold in E2+MPA treated cells. Our data show that the expression of genes from various functional gene families is regulated differentially by E2 and E2+MPA treatment in T47D cells. This suggests that exogenous progestins applied for therapy and endogenous changes of the progesterone levels during the menstrual cycle both influence breast cancer pathophysiology.

Breast Neoplasms↗