The Influence of Antenatal Partner Support on Pregnancy Outcomes

BACKGROUND: While there has been considerable attention given to the multitude of maternal factors that contribute to perinatal conditions and poor birth outcomes, few studies have aimed to understand the impact of fathers or partners. We examined associations of antenatal partner support with psychological variables, smoking behavior, and pregnancy outcomes in two socioeconomically distinct prebirth cohorts. MATERIALS AND METHODS: Data were from 1764 women recruited from an urban-suburban group practice (Project Viva) and 877 women from urban community health centers (Project ACCESS), both in the Boston area. Antenatal partner support was assessed by the Turner Support Scale. Multivariable linear and logistic regression analyses determined the impact of low antenatal partner support on the outcomes of interest. RESULTS: In early pregnancy, 6.4% of Viva and 23.0% of ACCESS participants reported low partner support. After adjustment, low partner support was cross-sectionally associated with high pregnancy-related anxiety in both cohorts (Viva AOR 1.8; 95% CI: 1.0-3.4 and ACCESS AOR 1.9; 95% CI: 1.1-3.3) and with depression in ACCESS (AOR 1.9; 95% CI: 1.1-3.3). In Viva, low partner support was also related to depression mid-pregnancy (AOR 3.1; 95% CI: 1.7-5.7) and to smoking (AOR 2.2; 95% CI: 1.3-3.8). Birth weight, gestational age, and fetal growth were not associated with partner support. CONCLUSIONS: This study of two economically and ethnically distinct cohorts in the Boston area highlights higher levels of antenatal anxiety, depression, and smoking among pregnant women who report low partner support. Partner support may be an important and potentially modifiable target for interventions to improve pregnancy outcomes

Association of the First 1,000 Days Systems-Change Intervention on Maternal Gestational Weight Gain

Objective: To examine the associations of a clinical and public health systems-change intervention on the prevalence of excess gestational weight gain among high-risk, low-income women. Methods: In a quasi-experimental trial, we compared the prevalence of excess gestational weight gain among women before (n=643) and after (n=928) implementation of the First 1,000 Days program in two community health centers in Massachusetts. First 1,000 Days is a systematic program starting in early pregnancy and lasting through the first 24 months of childhood to prevent obesity among mother-child pairs. The program includes enhanced gestational weight gain tracking and counseling, screening for adverse health behaviors and sociocontextual factors, patient navigation and educational materials to support behavior change and social needs, and individualized health coaching for women at high risk for excess gestational weight gain based on their prepregnancy body mass index (BMI) or excess first-trimester weight gain. The primary outcome was gestational weight gain greater than the 2009 Institute of Medicine (now known as the National Academy of Medicine) guidelines according to prepregnancy BMI. Results: Among 1,571 women in the analytic sample, mean (SD) age was 30.0 (5.9) years and prepregnancy BMI was 28.1 (6.1); 65.8% of women started pregnancy with BMIs of 25 or higher, and 53.2% were Hispanic. We observed a lower prevalence (55.8-46.4%; unadjusted odds ratio [OR] 0.69, 95% CI 0.49-0.97), similar to results in a multivariable analysis (adjusted OR 0.69, 95% CI 0.49-0.99), of excess gestational weight gain among women with prepregnancy BMIs between 25 and 29.9. Among women who were overweight at the start of pregnancy, the lowest odds of excess gestational weight gain were observed among those with the most interaction with the program's components. Program enrollment was not associated with reduced excess gestational weight gain among women with prepregnancy BMIs of 30 or higher. Conclusions: Implementation of a systems-change intervention was associated with modest reduction in excess gestational weight gain among women who were overweight but not obese at the start of pregnancy

Investigating the mechanism of action of hormones used in hormone replacement therapy via estrogen receptor subtypes and the influence of the progesterone receptor

Thesis (PhD)--Stellenbosch University, 2018.ENGLISH ABSTRACT: Estrogens and progestins used in conventional menopausal hormone therapy (HT) are associated with increased breast cancer risk. A diverse range of estrogens and progestins are available that mediate their effects primarily by binding to the estrogen receptor (ER) and progesterone receptor (PR), respectively. Although the link to breast cancer risk has not been shown for all estrogens and progestins, many women have turned to custom-compounded bioidentical hormone therapy (bHT) as it is claimed to not increase breast cancer risk. However, scientific evidence to support this claim is lacking. Estrogens and ERα are considered the main etiological factors driving breast cancer, while both ERα and the PR are required for progestin (medroxyprogesterone acetate (MPA)) effects on breast cancer cell proliferation. In this thesis, we investigated the activities of estrogens and progestins used in menopausal hormone therapies via the individual ER subtypes, and the role of ERα/PR crosstalk in mediating progestin-induced effects on gene expression, breast cancer cell proliferation and anchorage-independent growth. In the first part of the study, competitive whole cell bindings assays showed that bioidentical estradiol (bE2) and estriol (bE3) displayed similar binding affinities to the commercially available (natural) estradiol (E2) and estriol (E3) standards, while synthetic ethinylestradiol (EE) had a higher affinity for ERα, and natural E1 a lower affinity for ERβ. Furthermore, the bioidentical estrogens mimicked their respective natural estrogens and synthetic EE on transactivation and transrepression of gene expression, proliferation and anchorage-independent growth of the estrogen-sensitive MCF-7 BUS human breast cancer cell line. These assays showed that E3 and estrone (E1) are efficacious estrogens that do not antagonize E2. In the second part of this study, the estrogenic activities of selected progestins from different generations, MPA, norethisterone acetate (NET-A), levonorgestrel (LNG), gestodene (GES), nestorone (NES), nomegestrol acetate (NoMAC) and drospirenone (DRSP), were characterized relative to each other and natural progesterone (P4). Competitive binding assays revealed that only NET-A, LNG and GES could bind to ERα, while no progestin bound ERβ. Both transactivation and transrepression transcriptional assays showed that NETA, LNG and GES display estrogenic activity. In the third part of the study, the role of PR/ERα crosstalk in mediating the effects of MPA, NET and DRSP, relative to P4, on breast cancer cell proliferation, anchorage-independent growth and the expression of the ER-regulated trefoil factor 1 (pS2) and cathepsin D (CTSD) genes was investigated. All progestins could promote proliferation and anchorage-independent growth of MCF-7 BUS breast cancer cells to the same extent as P4 and E2 via a mechanism requiring both the PR and ERα, but DRSP was the least, and MPA the most potent for proliferation. Quantitative real-time RT-PCR (qPCR), chromatin immunoprecipitation (ChIP) and re-ChIP assays showed that only MPA and NET increased the expression of the pS2 and/or CTSD genes via a mechanism requiring co-recruitment of the PR and ERα to the promoter regions of these genes. In contrast, P4, MPA, NET and DRSP all caused recruitment of the PR/ERα complex to the PR-regulated oncogenes cyclin D1 and MYC. Taken together, the findings of this study suggest that there is no advantage in choosing bHT above conventional HT, and that while it is unlikely that the progestins used in this study will exert biological effects via ERα or ERβ in vivo, some progestins may increase breast cancer risk via a mechanism involving interplay between the PR and ERα.AFRIKAANSE OPSOMMING: Die gebruik van estrogene en progestiene in konvensionele menopousale hormoonterapie (HT) word geassosieër met ‘n toename in die risiko van borskanker. ‘n Verskeidenheid van estrogene en progestiene, wat hul effekte hoofsaaklik uitvoer deur die estrogeenreseptor (ER) en progesteroonreseptor (PR) onderskeidelik, is beskikbaar. Alhoewel die toenemende risiko van borskanker nog nie vir al die estrogene en progestiene getoon is nie, maak baie vrouens eerder gebruik van persoonlike saamgestelde bioidentiese hormoonterapie (bHT) aangesien daar beweer word dat dit nie borskanker risiko verhoog nie. Wetenskaplike bewyse om hierdie bewering te ondersteun is egter nie beskikbaar nie. Estrogene en ERα word beskou as die hoof etiologiese faktore wat borskanker dryf, terwyl beide ERα en die PR vir die effekte van progestien (medroksieprogesteroonasetaat (MPA)) op borskankerselproliferasie benodig word. In hierdie tesis, het ons die aktiwiteite van estrogene en progestiene, gebruik in menopousale hormoonterapies, deur die individuele ER subtipes ondersoek, asook die rol van ERα/PR wisselwerking in progestien-geïnduseerde geenuitdrukking, borskankerselproliferasie en geankerde-onafhanklike groei. In die eerste deel van die studie het kompeterende heelsel bindingstoetse getoon dat bioidentiese estradiool (bE2) en estriool (bE3) dieselfde bindingsaffiniteite het as die komersieël beskikbare (natuurlike) estradiool (E2) en estriool (E3) standaarde, terwyl sintetiese etinielestradiool (EE) ‘n hoër affiniteit vir ERα, en natuurlike estroon (E1) ‘n laer affiniteit vir ERβ het. Verder, boots die bioidentiese estrogene hul onderskeidelike natuurlike estrogene en sintetiese EE na in terme van transaktivering en transonderdrukking van geenuitdrukking, proliferasie en geankerde-onafhanklike groei van die estrogeen-sensitiewe MCF- 7 BUS menslike borskankersellyn. Hierdie toetse het getoon dat E3 and estroon (E1) doeltreffende estrogene is wat nie E2 antagoniseer nie. In die tweede deel van die studie was die estrogeniese aktiwiteite van geselekteerde progestiene van verskillende generasies, MPA, noretisteroonasetaat (NET-A), levonorgestrel (LNG), gestodeen (GES), nestoroon (NES), nomegestroolasetaat (NoMAC) en drospirenoon (DRSP), relatief tot mekaar en natuurlike progesteroon (P4), gekarakteriseer. Kompeterende bindingstoetse het aan die lig gebring dat slegs NET-A, LNG en GES aan ERα kon bind, terwyl geen van die progestiene ERβ bind nie. Beide transaktiverings- en transonderdrukkingstoetse het gewys dat NET-A, LNG en GES estrogeniese aktiwiteite toon. In die derde deel van die studie was die rol wat PR/ERα wisselwerking speel in die uitvoering van MPA, NET en DRSP, relatief tot P4, op borskankerselproliferasie, geankerde-onafhanklike groei en die uitdrukking van die ER-gereguleerde trefoiël faktor 1 (pS2) en katepsien D (CTSD) gene ondersoek. Al die progestiene kon proliferasie en geankerde-onafhanklike groei van die MCF-7 BUS borskankerselle tot dieselfde mate as P4 en E2 bevorder deur ‘n meganisme wat beide die PR en ERα benodig, maar DRSP was die minste, en MPA die meeste potent vir proliferasie. Kwantitatiewe intydse RT-PKR, kromatienimmunopresipitasie (ChIP) en her-ChIP toetse het getoon dat slegs MPA en NET die uitdrukking van die pS2 en/of CTSD gene verhoog deur ‘n meganisme wat die mede-werwing van die PR en ERα tot die promotor areas van hierdie gene vereis. In teendeel, P4, MPA, NET en DRSP het almal die werwing van die PR/ERα kompleks tot die PR-gereguleerde onkogene siklien D1 (CCND1) en MYC veroorsaak. In samevatting, die bevindinge van hierdie studie stel voor dat daar geen voordeel is om bHT te kies bo konvensionele HT nie, en alhoewel dit onwaarskynlik is dat die progestiene wat gebruik is in hierdie studie biologiese effekte deur ERα of ERβ sal uitvoer in vivo, mag sommige progestiene wel borskanker risiko verhoog deur ‘n meganisme wat wisselwerking tussen die PR en ERα behels

11-ketotestosterone and 11-ketodihydrotestosterone in castration resistant prostate cancer : potent androgens which can no longer be ignored

CITATION: Pretorius, E., et al. 2016. 11-ketotestosterone and 11-ketodihydrotestosterone in castration resistant prostate cancer : potent androgens which can no longer be ignored. PLoS ONE, 11(7):1-17, doi:10.1371/journal.pone.0159867.The original publication is available at http://journals.plos.org/plosonePublication of this article was funded by the Stellenbosch University Open Access Fund.Dihydrotestosterone (DHT) is regarded as the most potent natural androgen and is implicated in the development and progression of castration resistant prostate cancer (CRPC). Under castrate conditions, DHT is produced from the metabolism of the adrenal androgen precursors, DHEA and androstenedione. Recent studies have shown that the adrenal steroid 11β-hydroxyandrostenedione (11OHA4) serves as the precursor to the androgens 11-ketotestosterone (11KT) and 11-ketodihydrotestosterone (11KDHT). In this study we comprehensively assess the androgenic activity of 11KT and 11KDHT. This is the first study, to our knowledge, to show that 11KT and 11KDHT, like T and DHT, are potent and efficacious agonists of the human androgen receptor (AR) and induced both the expression of representative AR-regulated genes as well as cellular proliferation in the androgen dependent prostate cancer cell lines, LNCaP and VCaP. Proteomic analysis revealed that 11KDHT regulated the expression of more AR-regulated proteins than DHT in VCaP cells, while in vitro conversion assays showed that 11KT and 11KDHT are metabolized at a significantly lower rate in both LNCaP and VCaP cells when compared to T and DHT, respectively. Our findings show that 11KT and 11KDHT are bona fide androgens capable of inducing androgen-dependant gene expression and cell growth, and that these steroids have the potential to remain active longer than T and DHT due to the decreased rate at which they are metabolised. Collectively, our data demonstrates that 11KT and 11KDHT likely play a vital, but overlooked, role in the development and progression of CRPC.Publisher's versio

Reducing Hispanic Children’s Obesity Risk Factors in the First 1000 Days of Life: A Qualitative Analysis

Objectives. Modifiable behaviors during the first 1000 days (conception age 24 months) mediate Hispanic children’s obesity disparities. We aimed to examine underlying reasons for early life obesity risk factors and identify potential early life intervention strategies. Methods. We conducted 7 focus groups with 49 Hispanic women who were pregnant or had children < age 24 months. Domains included influences on childhood obesity risk factors and future intervention ideas. We analyzed data with immersion-crystallization methods until no new themes emerged. Results. Themes included coping with pregnancy may trump healthy eating and physical activity; early life weight gain is unrelated to later life obesity; fear of infant hunger drives bottle and early solids introduction; beliefs about infant taste promote early solids and sugary beverage introduction; and belief that screen time promotes infant development. Mothers identified physicians, nutritionists, and relatives as important health information sources and expressed interest in mobile technology and group or home visits for interventions. Conclusion. Opportunities exist in the first 1000 days to improve Hispanic mothers’ understanding of the role of early life weight gain in childhood obesity and other obesity risk factors. Interventions that link health care and public health systems and include extended family may prevent obesity among Hispanic children

The Role of Health Information Sources in Decision-Making Among Hispanic Mothers During Their Children’s First 1000 Days of Life

Objective This qualitative research aimed to explore how health information sources inform decision-making among Hispanic mothers during their children’s first 1000 days of life (conception-age 24 months), and to generate appropriate health information sources and communication strategies for future interventions. Methods We conducted 7 focus groups with 49 Hispanic women who were pregnant or had children < 2 years old. Domains included interpersonal and media sources, source trustworthiness, dealing with contradictory information, and how information affects decision-making. We used immersion/crystallization process for analysis. Results Trusted health information sources included health care providers, female and male family members, BabyCenter.com and other Internet sources, selected social media, and television. Some immigrant women reported preferring the Internet citing less established local support networks. Women highlighted the importance of validating health information through checking multiple sources for consistency and resolving contradictory information. Mothers expressed interest in receiving reliable website links from healthcare professionals and outreach to extended family. Conclusion Cultural factors, including immigration status, are important in understanding the use of health information sources and their role in decision-making about pregnancy and child health among Hispanic mothers. Healthcare providers and public health professionals should consider Hispanic mothers health information environment and provide culturally-relevant communication strategies and interventions during this high information-seeking time period

Reducing Hispanic Children's Obesity Risk Factors in the First 1000 Days of Life: A Qualitative Analysis

Objectives:. Modifiable behaviors during the first 1000 days (conception age 24 months) mediate Hispanic children's obesity disparities. We aimed to examine underlying reasons for early life obesity risk factors and identify potential early life intervention strategies. Methods:. We conducted 7 focus groups with 49 Hispanic women who were pregnant or had children < age 24 months. Domains included influences on childhood obesity risk factors and future intervention ideas. We analyzed data with immersion-crystallization methods until no new themes emerged. Results:. Themes included coping with pregnancy may trump healthy eating and physical activity; early life weight gain is unrelated to later life obesity; fear of infant hunger drives bottle and early solids introduction; beliefs about infant taste promote early solids and sugary beverage introduction; and belief that screen time promotes infant development. Mothers identified physicians, nutritionists, and relatives as important health information sources and expressed interest in mobile technology and group or home visits for interventions. Conclusion:. Opportunities exist in the first 1000 days to improve Hispanic mothers' understanding of the role of early life weight gain in childhood obesity and other obesity risk factors. Interventions that link health care and public health systems and include extended family may prevent obesity among Hispanic children