Publications

Sex and sensitivity: the continued need for sex-based biomedical research and implementation.

Sex and sensitivity: the continued need for sex-based biomedical research and implementation.

Womens Health (Lond Engl). 2010 Jul;6(4):511-6

Authors: Tingen CM, Kim AM, Wu PH, Woodruff TK

The phrase 'women's health research' embraces women as part of the biomedical research engine while categorizing women as separate. Before personalized medicine can become a reality, we must first ensure that basic physiological differences between the sexes are clearly delineated. In this article we argue that research into sex differences should be encouraged at the most fundamental levels of the biomedical sciences. Moreover, appropriate representation of both sexes as participants in clinical studies is still critically needed. Academic and governmental organizations must continue to articulate strong policy in order to ensure inclusion and analysis of sex as a critical variable. Focused attention on sex as a contributing factor to health, disease and therapeutic activity will increase our fund of knowledge regarding our everyday health, increase the pace of clinical research and ensure a healthier population.

PMID: 20597615 [PubMed - in process]

Sex bias in trials and treatment must end.

Sex bias in trials and treatment must end.

Nature. 2010 Jun 10;465(7299):688-9

Authors: Kim AM, Tingen CM, Woodruff TK

PMID: 20535184 [PubMed - in process]

Setting the Course: Leadership at the NICHD.

Setting the Course: Leadership at the NICHD.

Biol Reprod. 2010 Jun 2;

Authors: Woodruff TK

The NICHD has funded some of the most significant advances in child, maternal, and reproductive health in the 20th century. The new director must have a clear vision for the 21st century for improving health and health care through individual and team-based research and effectively communicate this vision to Congress and the public. This editorial outlines the requirements for new leadership of this Institute.

PMID: 20505167 [PubMed - as supplied by publisher]

The Oncofertility Consortium-addressing fertility in young people with cancer.

The Oncofertility Consortium-addressing fertility in young people with cancer.

Nat Rev Clin Oncol. 2010 May 25;

Authors: Woodruff TK

The number of young cancer survivors is increasing owing to advances in cancer therapeutics, but many face infertility as a result of their treatment. Technologies that already exist for cancer patients concerned about their future fertility include sperm banking for men and hormonal intervention followed by in vitro fertilization and embryo cryopreservation for women. However, logistical barriers to timely patient referral and coordination of care between specialties can limit patient access to all the available options. Moreover, there are few alternatives for young women and girls who cannot delay their cancer treatment, or who are unable to undergo hormonal intervention. The Oncofertility Consortium is a network of researchers, physicians and scholars who are advancing fertility preservation options for young cancer patients. Research into the societal, ethical, and legal implications is also an important part of the work performed by the Oncofertility Consortium, which is providing new perspectives on patient decision-making about how to access these emerging reproductive technologies. Experts in the fields of oncology, reproductive medicine, the social sciences, law, education, and the humanities are working together to develop next-generation reproductive interventions and promote communication between scholars, clinicians, patients, and the public to ensure that young cancer patients are equipped with the most appropriate information and options for having a family in the future.

PMID: 20498666 [PubMed - as supplied by publisher]

Using decision trees to enhance interdisciplinary team work: the case of oncofertility.

Using decision trees to enhance interdisciplinary team work: the case of oncofertility.

J Assist Reprod Genet. 2010 Apr 13;

Authors: Gardino SL, Jeruss JS, Woodruff TK

PURPOSE: Oncofertility, an emerging discipline at the intersection of cancer and fertility, strives to give cancer patients options when they are confronting potential infertility as a consequence of cancer treatment. Fertility preservation decisions must be made before treatment begins, adding stress to the decision-making process. METHODS: Healthcare providers need to be aware of the intricacies involved in oncofertility decision making, and the often tight time line that patients face when making these decisions. Cancer patient's perspectives may also change, as the dual burden of a cancer diagnosis and potential infertility can cause great flux in emotions. RESULTS: A provider-facing decision tree was created to enhance patient decision-making capacities and outline the multiple potential intervention points. CONCLUSIONS: Decision trees, which highlight the important decision points during which providers can approach patients, can be a useful tool to help providers in counseling patients on fertility preservation.

PMID: 20386978 [PubMed - as supplied by publisher]

Phylogenomic Analyses Reveal the Evolutionary Origin of the Inhibin alpha-Subunit, a Unique TGFbeta Superfamily Antagonist.

Phylogenomic Analyses Reveal the Evolutionary Origin of the Inhibin alpha-Subunit, a Unique TGFbeta Superfamily Antagonist.

PLoS One. 2010;5(3):e9457

Authors: Zhu J, Braun EL, Kohno S, Antenos M, Xu EY, Cook RW, Lin SJ, Moore BC, Guillette LJ, Jardetzky TS, Woodruff TK

Transforming growth factor-beta (TGFbeta) homologues form a diverse superfamily that arose early in animal evolution and control cellular function through membrane-spanning, conserved serine-threonine kinases (RII and RI receptors). Activin and inhibin are related dimers within the TGFbeta superfamily that share a common beta-subunit. The evolution of the inhibin alpha-subunit created the only antagonist within the TGFbeta superfamily and the only member known to act as an endocrine hormone. This hormone introduced a new level of complexity and control to vertebrate reproductive function. The novel functions of the inhibin alpha-subunit appear to reflect specific insertion-deletion changes within the inhibin beta-subunit that occurred during evolution. Using phylogenomic analysis, we correlated specific insertions with the acquisition of distinct functions that underlie the phenotypic complexity of vertebrate reproductive processes. This phylogenomic approach presents a new way of understanding the structure-function relationships between inhibin, activin, and the larger TGFbeta superfamily.

PMID: 20209104 [PubMed - as supplied by publisher]

Noninvasive Index of Cryorecovery and Growth Potential for Human Follicles In Vitro.

Noninvasive Index of Cryorecovery and Growth Potential for Human Follicles In Vitro.

Biol Reprod. 2010 Mar 3;

Authors: Barrett SL, Shea LD, Woodruff TK

Cryopreservation of oocytes and embryos is commonly used to preserve fertility. However, women undergoing cancer treatment may not have the time or may not be good candidates for these options. Ovarian cortical tissue cryopreservation and subsequent tissue transplant has been proven successful yet inefficient in preserving larger secondary follicles, and is not recommended as a fertility preservation option for women with certain cancers. We evaluated cryopreservation of individual follicles as an alternative option in rodents, non-human and human primates. Under optimal conditions, cryopreserved mouse secondary follicles were able to re-establish granulosa cell-oocyte interactions, which are essential for subsequent follicle growth. Individual secondary follicles survived cryopreservation, were able to be cultured in a 3D alginate hydrogel matrix to the antral stage, and the enclosed oocytes were competent for fertilization. Using a vital imaging technique (pol-scope) employed in many fertility centers, we were able to bioassay the thawed, cultured follicles for the presence of transzonal connections between the somatic and germ cells. Perturbations in these linkages were shown to be reversed when follicles were cryopreserved under optimal freezing conditions. We applied the optimized cryopreservation protocol to isolated rhesus monkey and human secondary follicles, and using the birefringent bioassay, we were able to show good correlation between early follicle growth and healthy somatic cell-oocyte connections. Our results suggest that ovarian follicles can be cryopreserved, thawed and analyzed non-invasively making follicle preservation an additional option for young cancer patients.

PMID: 20200211 [PubMed - as supplied by publisher]

The time is now for a new approach to primary ovarian insufficiency.

The time is now for a new approach to primary ovarian insufficiency.

Fertil Steril. 2010 Feb 24;

Authors: Cooper AR, Baker VL, Sterling EW, Ryan ME, Woodruff TK, Nelson LM

OBJECTIVE: To articulate the need for a new approach to primary ovarian insufficiency. The condition, also known as premature menopause or premature ovarian failure, is defined by the presence of menopausal-level serum gonadotropins in association with irregular menses in adolescent girls or women younger than 40 years. It can be iatrogenic as related to cancer therapy or may arise spontaneously, either alone or as part of a host of ultrarare syndromes. In a large percentage of spontaneous cases no pathogenic mechanism can be identified. DESIGN: Literature review and consensus building at a multidisciplinary scientific workshop. CONCLUSION(S): There are major gaps in knowledge regarding the etiologic mechanisms, psychosocial effects, natural history, and medical and psychosocial management of primary ovarian insufficiency. An international research consortium and disease registry formed under the guidance of an umbrella organization would provide a pathway to comprehensively increase basic and clinical knowledge about the condition. Such a consortium and patient registry also would provide clinical samples and clinical data with a goal toward defining the specific pathogenic mechanisms. An international collaborative approach that combines the structure of a patient registry with the principles of integrative care and community-based participatory research is needed to advance the field of primary ovarian insufficiency.

PMID: 20188353 [PubMed - as supplied by publisher]

The Illinois Women's Health Registry: advancing women's health research and education in Illinois, USA.

The Illinois Women's Health Registry: advancing women's health research and education in Illinois, USA.

Womens Health (Lond Engl). 2010 Mar;6(2):183-96

Authors: Bristol-Gould S, Desjardins M, Woodruff TK

To achieve the goal of personalized medicine, we must first improve our understanding of the differences in health and illness between men and women. The purpose of the Illinois Women's Health Registry (USA) is to provide a research and education tool that advances scientific knowledge of sex- and gender-based differences in health and disease. Specifically, the Registry is a confidential 30-min health and lifestyle survey for female residents of Illinois over the age of 18 years. The survey includes questions regarding health, environment, health-related behaviors, symptoms and illnesses or conditions that a participant may have now or has had in the past. By enrolling in the Registry, women throughout the state are provided with information and access to clinical research studies that they may be eligible for, based on their self-reported health information. The Registry not only serves as a platform for recruitment into pivotal research studies, but also represents the beginning of a state-wide database that enables researchers to examine the collective de-identified health information provided by women living in Illinois. Ultimately, a cross-sectional and longitudinal analysis of these data will help to clarify the issues that women themselves identify as their main health concerns. In response to these concerns, specific research studies can be designed and launched, allowing us to eventually deliver tailored treatment and prevention options to women. Finally, by creating a reliable state-focused research tool, developed by staff that are trained in women's health research, we can compare health issues across the state and apply strategies for improvement where it is needed most. This article will provide examples of sex differences in disease, the lack of federal enforcement for inclusion of women in studies, researcher-perceived burdens and sex-based reasons as to why recruitment of women is considered to be more challenging. In addition, this article will discuss what a women's health registry is and why we need one in Illinois, how we have recruited women and our successes and challenges. Our goal is to inform the reader about the utility of a state-based tool and to provide a discussion regarding the lessons learned in order to aid other states in implementing this kind of program.

PMID: 20187725 [PubMed - in process]

Altered sex hormone concentrations and gonadal mRNA expression levels of activin signaling factors in hatchling alligators from a contaminated Florida lakes.

Altered sex hormone concentrations and gonadal mRNA expression levels of activin signaling factors in hatchling alligators from a contaminated Florida lakes.

J Exp Zool A Ecol Genet Physiol. 2010 Feb 17;

Authors: Moore BC, Kohno S, Cook RW, Alvers AL, Hamlin HJ, Woodruff TK, Guillette LJ

Activins and estrogens participate in regulating the breakdown of ovarian germ cell nests and follicle assembly in mammals. In 1994, our group reported elevated frequencies of abnormal, multioocytic ovarian follicles in 6 month old, environmental contaminant-exposed female alligators after gonadotropin challenge. Here, we investigated if maternal contribution of endocrine disrupting contaminants to the egg subsequently alters estrogen/inhibin/activin signaling in hatchling female offspring, putatively predisposing an increased frequency of multioocytic follicle formation. We quantified basal and exogenous gonadotropin-stimulated concentrations of circulating plasma steroid hormones and ovarian activin signaling factor mRNA abundance in hatchling alligators from the same contaminated (Lake Apopka) and reference (Lake Woodruff) Florida lakes, as examined in 1994. Basal circulating plasma estradiol and testosterone concentrations were greater in alligators from the contaminated environment, whereas activin/inhibin betaA subunit and follistatin mRNA abundances were lower than values measured in ovaries from reference lake animals. Challenged, contaminant-exposed animals showed a more robust increase in plasma estradiol concentration following an acute follicle stimulating hormone (FSH) challenge compared with reference site alligators. Aromatase and follistatin mRNA levels increased in response to an extended FSH challenge in the reference site animals, but not in the contaminant-exposed animals. In hatchling alligators, ovarian follicles have not yet formed; therefore, these endocrine differences are likely to affect subsequent ovarian development, including ovarian follicle assembly. J. Exp. Zool. 313A, 2010. (c) 2010 Wiley-Liss, Inc.

PMID: 20166196 [PubMed - as supplied by publisher]