Acculturation, family cohesion, and mental health among Latinos living with HIV on the U.S.-Mexico border.

OBJECTIVE: The objective of the study was to investigate whether acculturation to U.S. culture is associated with greater posttraumatic stress disorder (PTSD) symptomatology through diminished family cohesion among Latinos living with HIV on the U.S.-Mexico border. METHOD: Baseline survey data were analyzed from a sample of Latinos seeking HIV care from a publicly funded HIV clinic in El Paso, Texas. We used a regression-based bootstrapping approach to test our mediation hypothesis. RESULTS: A total of 248 Latinos living with HIV completed the survey, with 96.4% being of Mexican descent, 19.4% female (gender self-identification), and 63.7% nonheterosexual (sexual orientation self-identification). Family cohesion mediated the relationship between U.S. acculturation and PTSD symptom scores (a1 ⁎ b1 = .03, 95% confidence interval [.01-.06]), an effect independent of acculturation to Latino culture. CONCLUSIONS: Acculturation to U.S. culture may negatively impact mental health through weakening family bonds in this vulnerable population. (PsycINFO Database Record

Factors Associated with Sexual Risk of HIV Transmission Among HIV-Positive Latino Men Who have Sex with Men on the U.S.-México Border.

We present results from a cross-sectional, clinic-based survey of border-region Latino men who have sex with men (MSM) and who also are living with HIV in the El Paso-Ciudad Juárez area. Among the 66 participants who reported serodiscordant anal or vaginal intercourse, we examined levels of psychological distress and substance use and the association of these variables with condomless sex. Bivariate analyses indicated that MSM who reported condomless sex with a serodiscordant partner were more likely to report higher scores on measures of anxiety, depression, and trauma. These men were also more likely to report more days of alcohol use to the point of intoxication. In multivariate logistic regression, no variables were independently associated with sexual risk behavior, but symptoms of anxiety trended toward statistical significance. Our study is one of few reports aimed at understanding the HIV epidemic among Latino MSM living with HIV in the El Paso-Ciudad Juárez border region. Although we found no evidence of a relation between our measures of psychological distress and substance use and sexual risk behavior in multivariate analyses, psychological distress and problematic alcohol use were common in the sample and are important targets for intervention in their own right.

Mechanism of action of the breast cancer-promoter hormone, 5α-dihydroprogesterone (5αP), involves plasma membrane-associated receptors and MAPK activation.

Previous studies have shown that breast tissues and breast cell lines can convert progesterone to 5α-pregnane-3,20-dione (5aP), and that 5αP stimulates breast cell proliferation and detachment in vitro, and tumor formation in vivo, regardless of presence or absence of receptors for progesterone (PR) or estrogen (ER). Recently it was demonstrated, both in vitro and in vivo, that pro-cancer actions attributed to administered progesterone are due to the in situ produced 5αP. Because of the significant role of 5αP in breast cancers, it is important to understand its molecular mechanisms of action. The aims of the current studies were to identify 5αP binding sites and to determine if the mechanisms of action of 5αP involve the mitogen-activated protein kinase (MAPK), extracellular signal-regulated protein kinases (ERK1/2) pathway. Binding studies, using tritium-labeled 5αP ([(3)H]5αP), carried out on membrane, cytosol and nuclear fractions from human breast cells (MCF-7, PR/ER-positive; MDA-MB-231, PR/ER-negative) and on highly enriched membrane fractions, identified the plasma membrane as the site of ligand specific 5αP receptors. Localization of 5αP receptors to the cell membrane was confirmed visually with fluorescently labeled conjugate (5αP-BSA-FITC). Treatment of cells with either 5αP or membrane-impermeable 5αP-BSA resulted in significant increases in cell proliferation and detachment. 5αP and 5αP-BSA equally activated the MAPK/ERK1/2 pathway as evidenced by phosphorylation of ERK1/2. Inhibitors (PD98059, mevastatin and genistein) of specific sites along the Ras/Raf/MEK/ERK signaling pathway, blocked the phosphorylation and concomitantly inhibited 5αP-induced stimulation of cell proliferation and detachment. The study has identified high affinity, stereo-specific binding sites for 5αP that have the characteristics of a functional membrane 5αP receptor, and has shown that the cancer-promoter actions of 5αP are mediated from the liganded receptor via the MAPK/ERK1/2 signaling cascade. The findings enhance our understanding of the role of the progesterone metabolite 5αP in breast cancer and should promote new approaches to the development of breast cancer diagnostics and therapeutics.

Childhood sexual abuse and depression in Latino men who have sex with men: Does resilience protect against nonadherence to antiretroviral therapy?

This study tested depression as a mediator between childhood sexual abuse and adherence to antiretroviral therapy, an effect moderated by resilience. In total, 149 HIV+ Latino men who have sex with men were recruited for this study. Using a regression-based bootstrap approach, depression mediated the relationship between childhood sexual abuse and antiretroviral therapy adherence, with worse adherence for participants at lowest percentiles of the resilience index. The prevalence of childhood sexual abuse and depression in HIV+ men who have sex with men is high and must be addressed to better prevent disease progression and reduce transmission, especially in expanding Latino populations.

Assessing the Gender Invariance of the Modern Homonegativity Scale.

The measurement invariance of the Modern Homonegativity Scale (MHS) was examined among heterosexual female (n = 449) and male (n = 329) university students who were predominantly Mexican American. The MHS demonstrated full invariance of factor loadings and partial invariance of latent intercepts. At the latent mean level, heterosexual men compared to heterosexual women held more negative attitudes toward both gay men and lesbian women. There were no latent mean differences in attitudes toward gay men and lesbian women when rated by either heterosexual men or heterosexual women. The MHS can be used by heterosexual men and heterosexual women to assess their homonegativity.

Progesterone-induced stimulation of mammary tumorigenesis is due to the progesterone metabolite, 5α-dihydroprogesterone (5αP) and can be suppressed by the 5α-reductase inhibitor, finasteride.

Progesterone has long been linked to breast cancer but its actual role as a cancer promoter has remained in dispute. Previous in vitro studies have shown that progesterone is converted to 5α-dihydroprogesterone (5αP) in breast tissue and human breast cell lines by the action of 5α-reductase, and that 5αP acts as a cancer-promoter hormone. Also studies with human breast cell lines in which the conversion of progesterone to 5αP is blocked by a 5α-reductase inhibitor, have shown that the in vitro stimulation in cell proliferation with progesterone treatments are not due to progesterone itself but to the metabolite 5αP. No similar in vivo study has been previously reported. The objective of the current studies was to determine in an in vivo mouse model if the presumptive progesterone-induced mammary tumorigenesis is due to the progesterone metabolite, 5αP. BALB/c mice were challenged with C4HD murine mammary cells, which have been shown to form tumors when treated with progesterone or the progestin, medroxyprogesterone acetate. Cells and mice were treated with various doses and combinations of progesterone, 5αP and/or the 5α-reductase inhibitor, finasteride, and the effects on cell proliferation and induction and growth of tumors were monitored. Hormone levels in serum and tumors were measured by specific RIA and ELISA tests. Proliferation of C4HD cells and induction and growth of tumors was stimulated by treatment with either progesterone or 5αP. The progesterone-induced stimulation was blocked by finasteride and reinstated by concomitant treatment with 5αP. The 5αP-induced tumors expressed high levels of ER, PR and ErbB-2. Hormone measurements showed significantly higher levels of 5αP in serum from mice with tumors than from mice without tumors, regardless of treatments, and 5αP levels were significantly higher (about 4-fold) in tumors than in respective sera, while progesterone levels did not differ between the compartments. The results indicate that the stimulation of C4HD tumor growth in BALB/c mice treated with progesterone is due to the progesterone metabolite 5αP formed at elevated levels in mammary cells as a result of the 5α-reductase action on progesterone. The results provide the first in vivo demonstration that stimulation of breast cell tumorigenesis and tumor growth accompanying progesterone treatment is due to the progesterone metabolite 5αP, and that breast tumorigenesis can be blocked with the 5α-reductase inhibitor, finasteride.

Simultaneous Development of a Multidimensional Fatalism Measure in English and Spanish.

Fatalism has been shown to predict several health behaviors, but researchers often find inconsistent results for the same behaviors across studies. This may be partially attributable to the diversity of fatalism measures that have been used in previous studies. A review of the literature revealed 51 different scales, all purported to measure fatalism, but often with heterogeneous content (Esparza 2005). A study done by Esparza (2005) retrieved 29 scales, including the most frequently used scales, and performed an exploratory factor analysis, obtaining as a result five factors: fatalism, helplessness, internality, luck, and divine control. The purpose of this study was to develop a multidimensional fatalism scale based on the previous findings by Esparza (2005). This scale was developed simultaneously in English and Spanish in order to linguistically "decenter" item content. The factor structure was cross-validated and measurement invariance was assessed across language versions. According to the measurement invariance analysis, this test is invariant across English and Spanish in its factor structure, loadings, variances, and covariances. This study results suggest that this scale may be used interchangeably in both English and Spanish.

A preliminary RCT of CBT-AD for adherence and depression among HIV-positive Latinos on the U.S.-Mexico border: the Nuevo Día study.

We conducted a preliminary RCT among 40 HIV-positive Latinos of Mexican descent on the U.S.-Mexico border who indicated imperfect adherence and depressive symptomatology. Participants were randomly assigned to culturally adapted cognitive-behavioral therapy for adherence and depression with an alarmed pillbox or usual care. Outcomes were depressive symptoms (self-report and blind clinician ratings), adherence (self-report and electronic pillbox), and biological markers. The intervention, delivered in English and Spanish, proved feasible and acceptable. Generalized estimating equations in intent-to-treat analyses showed some effects of "moderate" to "large" size, with maintenance over time. For example, intervention (vs. control) participants demonstrated at post-intervention a greater drop in BDI scores (OR = -3.64, p = 0.05) and greater adherence according to the electronic pillbox (OR = 3.78, p = 0.03). Biological markers indicated some relative improvement for CD4 count but not VL. The promising results suggest a larger trial to determine efficacy is warranted.

Progesterone metabolites regulate induction, growth, and suppression of estrogen- and progesterone receptor-negative human breast cell tumors.

INTRODUCTION: Of the nearly 1.4 million new cases of breast cancer diagnosed each year, a large proportion is characterized as hormone receptor negative, lacking estrogen receptors (ER) and/or progesterone receptors (PR). Patients with receptor-negative tumors do not respond to current steroid hormone-based therapies and generally have significantly higher risk of recurrence and mortality compared with patients with tumors that are ER- and/or PR-positive. Previous in vitro studies had shown that the progesterone metabolites, 5α-dihydroprogesterone (5αP) and 3α-dihydroprogesterone (3αHP), respectively, exhibit procancer and anticancer effects on receptor-negative human breast cell lines. Here in vivo studies were conducted to investigate the ability of 5αP and 3αHP to control initiation, growth, and regression of ER/PR-negative human breast cell tumors. METHODS: ER/PR-negative human breast cells (MDA-MB-231) were implanted into mammary fat pads of immunosuppressed mice, and the effects of 5αP and 3αHP treatments on tumor initiation, growth, suppression/regression, and histopathology were assessed in five separate experiments. Specific radioimmunoassays and gas chromatography-mass spectrometry were used to measure 5αP, 3αHP, and progesterone in mouse serum and tumors. RESULTS: Onset and growth of ER/PR-negative human breast cell tumors were significantly stimulated by 5αP and inhibited by 3αHP. When both hormones were applied simultaneously, the stimulatory effects of 5αP were abrogated by the inhibitory effects of 3αHP and vice versa. Treatment with 3αHP subsequent to 5αP-induced tumor initiation resulted in suppression of further tumorigenesis and regression of existing tumors. The levels of 5αP in tumors, regardless of treatment, were about 10-fold higher than the levels of 3αHP, and the 5αP:3αHP ratios were about fivefold higher than in serum, indicating significant changes in endogenous synthesis of these hormones in tumorous breast tissues. CONCLUSIONS: The studies showed that estrogen/progesterone-insensitive breast tumors are sensitive to, and controlled by, the progesterone metabolites 5αP and 3αHP. Tumorigenesis of ER/PR-negative breast cells is significantly enhanced by 5αP and suppressed by 3αHP, the outcome depending on the relative concentrations of these two hormones in the microenvironment in the breast regions. The findings show that the production of 5αP greatly exceeds that of 3αHP in ER/PR-negative tumors and that treatment with 3αHP can effectively block tumorigenesis and cause existing tumors to regress. The results provide the first hormonal theory to explain tumorigenesis of ER/PR-negative breast tissues and support the hypothesis that a high 3αHP-to-5αP concentration ratio in the microenvironment may foster normalcy in noncancerous breast regions. The findings suggest new diagnostics based on the relative levels of these hormones and new approaches to prevention and treatment of breast cancers based on regulating the levels and action mechanisms of anti- and pro-cancer progesterone metabolites.

Medication literacy in Spanish and English: psychometric evaluation of a new assessment tool.

OBJECTIVE: To evaluate the psychometric properties of a newly developed Medication Literacy Assessment in Spanish and English (MedLitR xSE). DESIGN: Descriptive, nonexperimental, cross-sectional study. SETTING: El Paso, TX, from December 2006 to June 2009. PARTICIPANTS: 181 English- or Spanish speaking adults. INTERVENTION: Survey administered in two phases. MAIN OUTCOME MEASURES: Descriptive statistics, internal consistency, confirmatory factor analysis (CFA) and fit indices, and criterion-related validity. RESULTS: The 20-item MedLitR xSE tool showed adequate internal consistency and reliability, and CFA revealed overall good model fit. In phase 2, the shorter 14-item MedLitR xSE showed good total test reliability and correlated well with the Short Test of Functional Health Literacy in Adults. Item response theory analyses showed no language bias and a one-dimensional (i.e., one factor) model of medication literacy. CONCLUSION: The initial and latest shorter version of the MedLitR xSE tool demonstrated good psychometric properties. This tool may provide a new option to assess "medication literacy" in English and Spanish.

The role of prospective memory in medication adherence: a review of an emerging literature.

Although neurocognitive impairment is an established risk factor for medication nonadherence, standard neurocognitive tests developed for clinical purposes may not fully capture the complexities of non-adherence behavior or effectively inform theory-driven interventions. Prospective memory, an innovative cognitive construct describing one's ability to remember to do something at a later time, is an understudied factor in the detection and remediation of medication non-adherence. This review orients researchers to the construct of prospective memory, summarizes empirical evidence for prospective memory as a risk factor for non-adherence, discusses the relative merits of current measurement techniques, and highlights potential prospective memory-focused intervention strategies. A comprehensive literature review was conducted of published empirical studies investigating prospective memory and medication adherence. Overall, reviewed studies suggest that prospective memory is an important component of medication adherence, providing incremental ecological validity over established predictors. Findings indicate that prospective memory-based interventions might be an effective means of improving adherence.

Decreased cytochrome c oxidase IV expression reduces steroidogenesis.

Steroidogenic acute regulatory protein facilitates the translocation of cholesterol to the inner mitochondrial membrane, thereby initiating steroidogenesis. At the inner mitochondrial membrane, cytochrome P450 side-chain cleavage enzyme converts cholesterol to pregnenolone, an oxidative process requiring electrons from NADPH. Pregnenolone then serves as the substrate for the formation of progesterone or dehydroepiandrosterone by downstream enzymes. Studies have shown that cigarette smoke (CS) influences steroid hormone levels. To better understand the underlying mechanisms, we used a mouse model to study the effects of chronic CS exposure on steroidogenesis. Through radioimmunoassay and metabolic conversion assays, we found that CS reduced progesterone and dehydroepiandrosterone without affecting cytochrome P450 side-chain cleavage enzyme or 3ß-hydroxysteroid dehydrogenase 2 expression. However, CS did reduce expression of cytochrome c oxidase IV (COX IV), a component of the mitochondrial complex that serves as the last enzyme in the electron transport chain. Small interfering RNA-mediated COX IV knockdown indeed decreased progesterone synthesis in steroidogenic cells. In summary, COX IV likely plays a role in steroidogenesis, and passive smoking may negatively affect steroidogenesis by disrupting the electron transport chain.

Culture and Probability Judgment Accuracy: The Influence of Holistic Reasoning.

A well-established phenomenon in the judgment and decision-making tradition is the overconfidence one places in the amount of knowledge that one possesses. Overconfidence or probability judgment accuracy varies not only individually but also across cultures. However, research efforts to explain cross-cultural variations in the overconfidence phenomenon have seldom been made. In Study 1, the authors compared the probability judgment accuracy of U.S. Americans (N = 108) and Mexican participants (N = 100). In Study 2, they experimentally primed culture by randomly assigning English/Spanish bilingual Mexican Americans (N = 195) to response language. Results of both studies replicated the cross-cultural variation of probability judgment accuracy previously observed in other cultural groups. U.S. Americans displayed less overconfidence when compared to Mexicans. These results were then replicated in bilingual participants, when culture was experimentally manipulated with language priming. Holistic reasoning did not account for the cross-cultural variation of overconfidence. Suggestions for future studies are discussed.

Opposing actions of the progesterone metabolites, 5alpha-dihydroprogesterone (5alphaP) and 3alpha-dihydroprogesterone (3alphaHP) on mitosis, apoptosis, and expression of Bcl-2, Bax and p21 in human breast cell lines.

Previous studies have shown that breast tissues and breast cell lines convert progesterone (P) to 5alpha-dihydroprogesterone (5alphaP) and 3alpha-dihydroprogesterone (3alphaHP) and that 3alphaHP suppresses, whereas 5alphaP promotes, cell proliferation and detachment. The objectives of the current studies were to determine if the 5alphaP- and 3alphaHP-induced changes in cell numbers are due to altered rates of mitosis and/or apoptosis, and if 3alphaHP and 5alphaP act on tumorigenic and non-tumorigenic cells, regardless of estrogen (E) and P receptor status. The studies were conducted on tumorigenic (MCF-7, MDA-MB-231, T47D) and non-tumorigenic (MCF-10A) human breast cell lines, employing several methods to assess the effects of the hormones on cell proliferation, mitosis, apoptosis and expression of Bcl-2, Bax and p21. In all four cell lines, 5alphaP increased, whereas 3alphaHP decreased cell numbers, [(3)H]thymidine uptake and mitotic index. Apoptosis was stimulated by 3alphaHP and suppressed by 5alphaP. 5alphaP resulted in increases in Bcl-2/Bax ratio, indicating decreased apoptosis; 3alphaHP resulted in decreases in Bcl-2/Bax ratio, indicating increased apoptosis. The effects of either 3alphaHP or 5alphaP on cell numbers, [(3)H]thymidine uptake, mitosis, apoptosis, and Bcl-2/Bax ratio, were abrogated when cells were treated simultaneously with both hormones. The expression of p21 was increased by 3alphaHP, and was unaffected by 5alphaP. The results provide the first evidence that 5alphaP stimulates mitosis and suppresses apoptosis, whereas 3alphaHP inhibits mitosis and stimulates apoptosis. The opposing effects of 5alphaP and 3alphaHP were observed in all four breast cell lines examined and the data suggest that all breast cancers (estrogen-responsive and unresponsive) might be suppressed by blocking 5alphaP formation and/or increasing 3alphaHP. The findings further support the hypothesis that progesterone metabolites are key regulatory hormones and that changes in their relative concentrations in the breast microenvironment determine whether breast tissues remain normal or become cancerous.

A health survey of a colonia located on the west Texas, US/Mexico border.

Little is known about how health disparities affect the health status and general health perceptions of Hispanics living in Texas colonias. The purpose of this study was to conduct a health survey of residents (n = 216) of a colonia community on the border between El Paso, Texas and Juarez, Mexico. Instruments used in this study included a researcher developed demographic questionnaire, the Short Acculturation Scale for Hispanics (SASH), Cutting down, Annoyance by criticism, Guilty feeling and Eye-openers (CAGE) for alcohol consumption, and the Short Form version 2 (SF36v2) health survey. Study findings show the average participant was approximately 42 years old, attained an average of 9.6 years of education, earned an average annual household income of $17,575 and had an average SASH score of 25.4. SASH scores range from 12 to 60, with higher scores suggesting higher levels of American acculturation. Findings from this health survey suggest the average resident of the colonia may have health disadvantages when compared to residents from other parts of El Paso and Texas. Binge drinking was self-reported by 13.4% of all participants; with 5.6% having a CAGE score greater than 2 (indicating an increased propensity towards problems with alcohol). The self-report rates of diabetes, depression and anxiety were 15.3%, 20.4% and 16.7% respectively. The SF36v2 composite functional health status scores mirrored the national norms.

An event-level analysis of condom use as a function of mood, alcohol use, and safer sex negotiations.

Daily self-reports of condom-protected intercourse were analyzed as a function of emotional states, alcohol consumption, and safer sex negotiations in a sample of single, low-income Hispanic students. The sample included 15 women and 17 men who reported a minimum of four sexual episodes as well as inconsistent condom use over a 3-month self-reporting period. The analyses focused on 829 days out of 2,586 daily self-reports on which sexual intercourse was reported. Hierarchical linear modeling was used to predict condom-protected intercourse as a function of mood states, substance use, and safer sex negotiations. Safer sex negotiation was the strongest positive predictor of condom use. Contrary to expectation, unprotected intercourse was less likely to occur in episodes characterized by greater negative affect and more likely in episodes in which greater positive mood was reported. No main effect of alcohol consumption on safer sex was observed; however, an interaction between alcohol consumption and positive mood emerged, indicating that unprotected intercourse was most likely to occur when positive mood was combined with alcohol consumption. The results contradict the assumption that emotional distress predicts engagement in more risky sexual behavior and indicate that safer sex negotiations are likely to outweigh any effects of mood or alcohol consumption on subsequent condom use.

Can language prime culture in Hispanics? The differential impact of self-construals in predicting intention to use a condom.

The highly influential theory of planned behavior suggests that norms and attitudes predict an important antecedent of behavior: intention. Cross-cultural research suggests that culturally influenced self-construals can be primed and differentially affect behaviors that are influenced by norms and attitudes. The purpose of this experiment was twofold: (1) To investigate whether language functions as a prime for culture in Hispanics, and (2) if so, if norms and attitudes differentially predict condom use intention. Fluent English-Spanish bilingual participants (N = 145) of Mexican descent were randomly assigned to answer questionnaires in English and Spanish. Subjective norms and private evaluations towards condom use were assessed and their relative strength in predicting condom use intention was evaluated. Results suggest that language can prime culture and affect the relative accessibility of culture-relevant norms and self-construals in Hispanics. Moreover, consistent with our expectations, norms and attitudes differentially predicted condom use intention.

Diabetes prevalence and treatment adherence in residents living in a colonia located on the West Texas, USA/Mexico border.

Little is known about how diabetes affects the health status of Hispanic people living in colonias located along the USA/Mexico border. The purpose of this report is to describe the demographic factors, prevalence of diabetes, and the health status of the residents living in a colonia on the border between El Paso, Texas, USA, and Juarez, Mexico, and to report the residents' adherence to the Behavioral Risk Factor Surveillance System (BRFSS) protocols for the management of type 2 diabetes. This study included 188 participants. The instruments used included a demographic questionnaire, the Short Acculturation Scale for Hispanics, "Cutting Down, Annoyance by Criticism, Guilty Feelings, and Eye-openers", BRFSS, and the Short Form-36 (v2). The prevalence of diabetes was 15.4% and 41.3% of the residents had a Body Mass Index score > 30. The rate of hypertension, elevated cholesterol, and depression for those reporting diabetes was significant. The SF-36 v2 physical score for the diabetic residents was 42.9 and it was 52.4 for the non-diabetic residents. The average resident of the colonia who reports diabetes has many health disadvantages when compared to those in other parts of Texas and the USA generally.

Interactive Voice Response Technology applied to sexual behavior self-reports: a comparison of three methods.

We tested the feasibility and performance of the Interactive Voice Response Technology (IVR) in the assessment of sexual behavior self-reports, relative to self-administered questionnaire (SAQ) and Timeline Followback (TLFB) methods. The sample consisted of 44 sexually active Hispanic students recruited at the University of Texas at El Paso who reported daily about sexual behaviors and substance use. Thirty-three participants (75%, 18 women, 15 men) were retained for at least 80 days of the 91-day IVR. At follow-up, sexual behaviors and substance use were assessed by questionnaire (summary) reports and by TLFB, referring to the same 3-month interval. ANOVAs with normalized variables indicated less reporting in the TLFB and over-reporting of substance use in the questionnaire relative to the daily IVR self-reports. Gender moderated the effects of assessment mode, which were observed among women only. HLM analyses indicated a significant decrease in self-reports over time, suggesting reactivity of self-monitoring via IVR on behavior.

Progesterone metabolites in breast cancer.

In the 70 years since progesterone (P) was identified in corpus luteum extracts, its metabolism has been examined extensively in many tissues and cell lines from numerous species. In addition to the reproductive tissues and adrenals, every other tissue that has been investigated appears to have one or more P-metabolizing enzyme, each of which is specific for a particular site on the P molecule. In the past, the actions of the P metabolizing enzymes generally have been equated to a means of reducing the P concentration in the tissue microenvironment, and the products have been dismissed as inactive waste metabolites. In human breast tissues and cell lines, the following P-metabolizing enzymes have been identified: 5alpha-reductase, 3alpha-hydroxysteroid oxidoreductase (3alpha-HSO), 3beta-HSO, 20alpha-HSO, and 6alpha-hydroxylase. Rather than providing diverse pathways for inactivating and controlling the concentration of P in breast tissue microenvironments, it is proposed that the enzymes act directly on P to produce two types of autocrines/paracrines with opposing regulatory roles in breast cancer. Evidence is reviewed which shows that P is directly converted to the 4-pregnenes, 3alpha-hydroxy-4-pregnen-20-one (3alpha-dihydroprogesterone; 3alphaHP) and 20alpha-dihydroprogesterone (20alphaHP), by the actions of 3alpha-HSO and 20alpha-HSO respectively and to the 5alpha-pregnane, 5alpha-pregnane-3,20-dione(5alpha-dihydroprogesterone; 5alphaP), by the irreversible action of 5alpha-reductase. In vitro studies on a number of breast cell lines indicate that 3alphaHP promotes normalcy by downregulating cell proliferation and detachment, whereas 5alphaP promotes mitogenesis and metastasis by stimulating cell proliferation and detachment. The hormones bind to novel, separate, and specific plasma membrane-based receptors and influence opposing actions on mitosis, apoptosis, and cytoskeletal and adhesion plaque molecules via cell signaling pathways. In normal tissue, the ratio of 4-pregnenes:5alpha-pregnanes is high because of high P 3alpha- and 20alpha-HSO activities/expression and low P 5alpha-reductase activity/expression. In breast tumor tissue and tumorigenic cell lines, the ratio is reversed in favor of the 5alpha-pregnanes because of altered P-metabolizing enzyme activities/expression. The evidence suggests that the promotion of breast cancer is related to changes in in situ concentrations of cancer-inhibiting and -promoting P metabolites. Current estrogen-based theories and therapies apply to only a fraction of all breast cancers; the majority (about two-thirds) of breast cancer cases are estrogen-insensitive and have lacked endocrine explanations. As the P metabolites, 5alphaP and 3alphaHP, have been shown to act with equal efficacy on all breast cell lines tested, regardless of their tumorigenicity, estrogen sensitivity, and estrogen receptor/progesterone receptor status, it is proposed that they offer a new hormonal basis for all forms of breast cancer. New diagnostic and therapeutic possibilities for breast cancer progression, control, regression, and prevention are suggested.