74 Search Results for "drug use prevention"
Since 2017, NIH’s Office of Research on Women’s Health (ORWH) has hosted the Vivian W. Pinn Symposium during National Women’s Health Week (NWHW) in May. This event honors the first full-time director of the office, Dr. Vivian W. Pinn, and serves as a critical forum for experts across sectors to communicate and collaborate for the advancement of women’s health.
This week marks the beginning of the 2023 NWHW, and on May 16, ORWH will host the 7th Annual Vivian W. Pinn Symposium. It’s titled: Menopause and Optimizing Midlife Health of Women.
Topics to be discussed include: the menopausal transition (also known as perimenopause), the accumulation of morbidity after menopause, menopause in special populations, the influence of social determinants of health on the experience of menopause, the use of menopausal hormone therapy (MHT), and interventions to promote healthy aging.
This year, JoAnn Manson, Harvard Medical School, Cambridge, MA, will deliver the keynote speech, titled “Menopausal Hormone Therapy: 30 Years of Lessons from the Women’s Health Initiative.” I encourage everyone with an interest in women’s health to register for the event.
In 1992, NIH’s National Heart, Lung, and Blood Institute launched the Women’s Health Initiative (WHI), seeking to improve the health of women through research on prevention of serious health conditions in postmenopausal women. Over three decades later, WHI remains an extraordinary example of centering research around the health needs of women, and WHI research results “definitively established that menopausal hormone therapy should not be used to prevent heart disease, stroke, and other chronic diseases.” These results were practice-changing and led to a dramatic decline in the use of MHT.
Menopause is a natural and irreversible life course stage marked by the cessation of menstrual cycling for 12 consecutive months. Common symptoms associated with menopause include hot flashes, sleep disturbances, mood changes, headaches, and heart palpitations. An article, co-authored by Dr. Manson, summarizes effective hormonal and non-hormonal treatments to manage menopausal symptoms .
The WHI’s longer-term follow-up of the treatment of these women, however, has demonstrated many nuanced findings . For example, MHT’s risks and benefits are complex and vary based upon patient-level characteristics, including the age at which the therapy is initiated and the formulation of the MHT prescribed. Importantly, WHI was designed to assess the efficacy of MHT in preventing chronic disease, not to assess the efficacy or safety of MHT when used to treat menopausal symptoms. The average study participant was older, with over a decade since the start of their menopausal transition.
When considering any treatment, people should consult a health care professional, and MHT may be an option for some women, especially those who are experiencing menopausal symptoms and are at low risk for adverse events. The Food and Drug Administration (FDA) offers a fact sheet to answer questions and provide guidance about menopause and hormones, and has evaluated the risks and benefits of MHT for specific age groups of women .
In addition to WHI, there are two other valuable NIH-funded studies helping to make progress in our understanding of the health of midlife and older women:
A major health concern for women during perimenopause, menopause, and post menopause is cardiovascular health. More research is needed to understand how different stages of menopause affect women’s cardiovascular health and how different doses and formulations of MHT may affect risk.
Among the many speakers at the Vivian W. Pinn Symposium will be Wendy Kohrt, a co-author on a recent comprehensive review of cardiovascular health and menopause . She is director of the University of Colorado Specialized Centers of Research Excellence on Sex Differences (SCORE), Aurora. Also, a recent issue of ORWH’s Women’s Health in Focus at NIH discussed current NIH-funded research on menopause, resources, future menopause-related research, and more.
In response to a Congressional request to address NIH efforts related to women’s health research, ORWH hosted, along with the NIH Advisory Committee on Research on Women’s Health, “Advancing NIH Research on the Health of Women: A 2021 Conference.” The importance of menopause research as it relates to chronic debilitating conditions, which pose a significant burden on the health of women, was addressed during the conference, and the full report is available on the ORWH website.
Further, ORWH and partnering institutes released two notices of funding opportunities titled Understanding Chronic Conditions Understudied Among Women (R01 and R21), and ORWH sponsored the forthcoming Framework for the Consideration of Chronic Debilitating Conditions in Women from the National Academies of Sciences, Engineering, and Medicine.
I wish everyone a happy and healthy NWHW and look forward to gathering virtually for the 7th Annual Vivian W. Pinn Symposium. For more information and resources on menopause, visit the FDA’s Office of Women’s Health and NIH’s National Institute on Aging (NIA) websites. Also, My Menoplan, developed by NIA-funded researchers, offers information and personalized tools to help plan for perimenopause and menopause. Please stay connected to ORWH by visiting our website for updates; signing up for our monthly newsletter, The Pulse; liking us on Facebook; and following ORWH on Twitter.
 Management of menopausal symptoms: A review. Crandall CJ, et al. JAMA. 2023 February 7: 329(5):405-420.
 Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women’s Health Initiative randomized trials. Manson JE, et al. JAMA. 2013 October 2: 310(13)1353-1368.
 Randomized trial evaluation of the benefits and risks of menopausal hormone therapy among women 50-59 years of age. Prentice RL, et al. Am J Epidemiol. 2021 February 1: 190(3):365-375.
 Body composition and cardiometabolic health across the menopause transition. Marlatt KL, et al. Obesity. 2022 January; 30(1)14-27.
National Women’s Health Week (Office on Women’s Health, U.S. Department of Health and Human Services, Rockville, MD)
Menopause Strategies: Finding Lasting Answers for Symptoms and Health (MsFLASH) (Fred Hutchinson Cancer Center, Seattle)
Office of Women’s Health (U.S. Food and Drug Administration, Silver Spring, MD)
Note: Dr. Lawrence Tabak, who performs the duties of the NIH Director, has asked the heads of NIH’s Institutes, Centers, and Offices to contribute occasional guest posts to the blog to highlight some of the interesting science that they support and conduct. This is the 30th in the series of NIH guest posts that will run until a new permanent NIH director is in place.
Posted on by Dr. Francis Collins
Despite continued progress in treatment and prevention, lung cancer remains our nation’s leading cause of cancer death. In fact, more Americans die of lung cancer each year than of breast, colon, and prostate cancers combined [1,2]. While cigarette smoking is a major cause, lung cancer also occurs in non-smokers. I’m pleased to report discovery of what we hope will be a much-needed drug target for a highly aggressive, difficult-to-treat form of the disease, called small cell lung cancer (SCLC).
Using gene-editing technology to conduct a systematic, large-scale search for druggable vulnerabilities in certain types of cancer cells grown in lab dishes, NIH-funded researchers recently identified a metabolic pathway that appears to play a key role in SCLC. What makes this news even more encouraging is drugs that block this pathway already exist. That includes one in clinical testing for other types of cancer, and another that’s FDA-approved and has been safely used for more than 20 years to treat people with rheumatoid arthritis.
The new work comes from the lab of Tyler Jacks, Massachusetts Institute of Technology (MIT), Cambridge. The Jacks lab, which is dedicated to understanding the genetic events that lead to cancer, develops mouse models engineered to carry the same genetic mutations that turn up in human cancers.
In work described in Science Translational Medicine, the team, co-led by Leanne Li and Sheng Rong Ng, applied CRISPR gene-editing tools to cells grown from some of their mouse models. Aiming high in terms of scale, researchers used CRISPR to knock out systematically, one by one, each of about 5,000 genes in cells from the SCLC mouse model, as well in cells from mouse models of other types of lung and pancreatic cancers. They looked to see what gene knockouts would slow down or kill the cancer cells, because that would be a good indication that the protein products of these genes, or the pathways they mediated, would be potential drug targets.
Out of those thousands of genes, one rose to the top of the list. It encodes an enzyme called DHODH (dihydroorotate dehydrogenase). This enzyme plays an important role in synthesizing pyrimidine, which is a major building block in DNA and RNA. Cytosine and thymine, the C and T in the four-letter DNA code, are pyrimidines; so is uracil, the U in RNA that takes the place of T in DNA. Because cancer cells are constantly dividing, there is a continual need to synthesize new DNA and RNA molecules to support the production of new daughter cells. And that means, unlike healthy cells, cancer cells require a steady supply of pyrimidine.
It turns out that the SCLC cells have an unexpected weakness relative to other cancer cells: they don’t produce as much pyrimidine. As a result, the researchers found blocking DHODH left the cells short on pyrimidine, leading to reduced growth and survival of the cancer.
This was especially good news because DHODH-blocking drugs, including one called brequinar, have already been tested in clinical trials for other cancers. In fact, brequinar is now being explored as a potential treatment for acute myeloid leukemia.
Might brequinar also hold promise for treating SCLC? To explore further, the researchers looked again to their genetic mouse model of SCLC. Their studies showed that mice treated with brequinar lived about 40 days longer than control animals. That’s a significant survival benefit in this system.
Brequinar treatment appeared to work even better when combined with other approved cancer drugs in mice that had SCLC cells transplanted into them. Further study in mice carrying SCLC tumors derived from four human patients added to this evidence. Two of the four human tumors shrunk in mice treated with brequinar.
Of course, mice are not people. But the findings suggest that brequinar or another DHODH blocker might hold promise as a new way to treat SCLC. While more study is needed to understand even better how brequinar works and explore potentially promising drug combinations, the fact that this drug is already in human testing for another indication suggests that a clinical trial to explore its use for SCLC might happen more quickly.
More broadly, the new findings show the promise of gene-editing technology as a research tool for uncovering elusive cancer targets. Such hard-fought discoveries will help to advance precise approaches to the treatment of even the most aggressive cancer types. And that should come as encouraging news to all those who are hoping to find new answers for hard-to-treat cancers.
 Cancer Stat Facts: Lung and Bronchus Cancer (National Cancer Institute/NIH)
 Key Statistics for Lung Cancer (American Cancer Society)
 Identification of DHODH as a therapeutic target in small cell lung cancer. Li L, Ng SR, Colón CI, Drapkin BJ, Hsu PP, Li Z, Nabel CS, Lewis CA, Romero R, Mercer KL, Bhutkar A, Phat S, Myers DT, Muzumdar MD, Westcott PMK, Beytagh MC, Farago AF, Vander Heiden MG, Dyson NJ, Jacks T. Sci Transl Med. 2019 Nov 6;11(517).
Small Cell Lung Cancer Treatment (NCI/NIH)
Tyler Jacks (Massachusetts Institute of Technology, Cambridge)
NIH Support: National Cancer Institute