Abstract
A new study from researchers at UCLA suggests that a widely used class of chemicals may be linked to infertility in women
A recent study published in the journal Human Reproduction suggests that perfluorinated chemicals (PFCs), widely used in developed countries, may be responsible for reducing fertility in women. Researchers from the University of California in Los Angeles (UCLA), USA, measured levels of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in blood samples that were taken from 1240 pregnant Danish women from 1996 to 2002. Led by Jørn Olsen, the team found that those with higher levels of the PFCs in their blood had taken longer to become pregnant than those with the lowest levels. PFCs are useful in industry because of their resistance to heat and their ability to repel water and oil. These qualities make them ideal for use in products such as fire-fighting foams, food wrappings, pesticides, carpets, upholstery and as industrial surfactants. However, high concentrations have been linked to organ damage in animals, and the chemicals have the ability to persist for long periods in the body.
In the study, blood samples taken at the time of the woman's first antenatal visit were analyzed for PFOS/PFOA concentrations. At week 12 of pregnancy, the women were interviewed in order to ascertain whether the pregnancy was planned, and how long it had taken them to become pregnant.
Levels of PFOS in the women's plasma ranged from 6.4 to 106.7 ng/ml, and from less than 1 to 41.5 ng/ml for PFOA. The women's levels of PFOS/PFOA were divided into four quartiles, and the researchers found that, compared with women with the lowest levels of exposure, the likelihood of infertility increased by 70–134% for women in the higher three quartiles of PFOS exposure and by 60–154% for women in the higher three quartiles of PFOA exposure.
First author of the study, Chunyuan Fei from UCLA, commented: “PFOS and PFOA were considered to be biologically inactive, but recently animal studies have shown that these chemicals may have a variety of toxic effects on the liver, immune system and developmental and reproductive organs. Very few human studies have been done, but one of our earlier studies showed that PFOA, although not PFOS, may impair the growth of babies in the womb, and another two epidemiological studies linked PFOA and PFOS to impaired foetal growth.”
Olsen, Chair of the Department of Epidemiology at UCLA, remarks: “As far as we know, this is the first study to assess the associations between PFOA and PFOS levels in plasma with time to pregnancy in humans. We are waiting for further studies to replicate our findings in order to discover whether PFCs should be added to the list of risk factors for infertility.”
The researchers suggest that PFCs may interfere with hormones that are involved in reproduction. However, these mechanisms remain to be elucidated. “Our data showed that higher proportions of women reported irregular menstrual periods in the upper three quartiles of PFOA and PFOS compared with the lowest, and so this could indicate a possible pathway,” added Fei.
In addition, Olsen cautions that this is preliminary research and “[the study] really needs to be replicated before we can make any firm conclusion about whether these compounds really do affect fertility.”
Source: Fei C, McLaughlin JK, Lipworth L, Olsen J: Maternal levels of perfluorinated chemicals and subfecundity. Hum. Reprod. DOI: 10.1093/humrep/den490 (2009) (Epub ahead of print).
in brief…
Oeffinger KC, Ford JS, Moskowitz CS et al.: JAMA 28, 301(4), 404–414 (2009).
Between June 2005 and August 2006, a 114-item questionnaire was administered to a random sample of 625 women aged 25–50 years who had survived pediatric cancer treated with chest radiation, and who were participating in the Childhood Cancer Survivor Study (CCSS). Comparisons were made with pediatric cancer survivors of a similar age who were not treated with chest radiation (n = 639) and the CCSS siblings cohort (n = 712). Among the women with a history of chest radiation, (n = 551) 55% reported a screening mammogram in the past 2 years, 47.3% of those younger than 40 years had never had a mammogram and only 52.6% of women aged 40–50 years were being regularly screened (two mammograms within 4 years). A total of 40.5% of survivors without chest radiation and 37.0% of CCSS siblings reported a screening mammogram in the same time interval. Despite a guideline recommendation that survivors of childhood cancer who were treated with chest radiation should undergo annual screening mammography, in this cohort of women, 63.5% of those aged 25–39 years and 23.5% of those aged 40–50 years who had childhood cancer treated with chest radiation had not had mammography screening for breast cancer within the previous 2 years.
Jensen A, Sharif H, Frederiksen K, Krüger Kjær S: Br. Med. J. DOI: 10.1136/bmj. b249 (2009) (Epub ahead of print).
A total of 54,362 women with infertility problems who were referred to all Danish fertility clinics during 1963–1998 were studied in to order examine the effects of fertility drugs on overall risk of ovarian cancer. The median age at first evaluation of infertility was 30 years and the median age at the end of follow-up was 47 years. A total of 156 women with invasive epithelial ovarian cancer (cases) and 1241 subcohort members identified in the cohort during follow-up in 2006 were included in the analysis. Researchers measured the effect of four groups of fertility drugs (gonadotrophins, clomifene citrate, human chorionic gonadotrophin and gonadotrophin releasing hormone) on overall risk of ovarian cancer following adjustment for potential confounding factors. Analyses within the cohort demonstrated no overall increased risk of ovarian cancer after use of any of the fertility drugs studied. In addition, no associations were found between all four groups of fertility drugs and number of cycles of use, length of follow-up or parity.
Surgeons successfully remove healthy kidney through donor's vagina
In what is believed to be a world-first, surgeons at Johns Hopkins University (MA, USA) have successfully removed a healthy kidney through a small incision in the back of a donor's vagina, eliminating the need for the 5–6 inch abdominal incision associated with conventional laparoscopic methods and leaving the patient with minimal scarring.
With approximately 6000 transplant donor nephrectomies carried out each year in the USA alone, it is hoped that the ease with which this method is able to be performed will encourage more women to consider organ donation.
Mohamad E Allaf, at Johns Hopkins University, performed this procedure, which involved the insertion of “wandlike cameras and tools” through small incisions in the abdomen and navel. The kidney is cut from its attachments to the abdominal wall and the arteries and veins are subsequently stapled shut. The kidney, enclosed in a plastic bag, is passed through an incision in the vaginal wall and pulled out through the vaginal opening via an attached string. To sterilize the procedure, the vagina is treated with Betadine® (Purdue Pharma, LP, CT, USA).
Robert Montgomery, Chief of the Transplant Division at the university's medical school, comments: “Removing the kidney through a natural opening should hasten the patient's recovery and provide a better cosmetic result.”
Source: John Hopkins Medicine press release. www.hopkinsmedicine.org/Press_releases/2009/02_02_09.html
Misfolded proteins in urine may provide clues to underlying cause of pre-eclampsia
Researchers at Yale University (CT, USA) have devised a simple test that may have the potential to predict the risk of pre-eclampsia in pregnant women through the identification of misfolded proteins in the urine. Lead author, Irina Buhimschi, hopes that this new technique will allow early the diagnosis of this poorly understood disease.
“This novel identification of pre-eclampsia … may lead to testing of new drugs or developing new therapies.”
In a study investigating 111 pregnant women, Buhimschi and colleagues analyzed the urine of these participants, beginning in the first trimester of pregnancy. The team applied a dye that stuck to misfolded proteins and from this, were able to predict which of the women went on the suffer pre-eclampsia and undergo early delivery.
Buhimschi believes that: “This novel identification of pre-eclampsia as a disorder of protein misfolding opens a door for researchers that may lead to testing of new drugs or developing new therapies. Our future work will seek to determine whether the different shapes employed by the mis-folded proteins in pre-eclampsia are linked to specific clinical symptoms and the different ways this intriguing disease manifests.
Source: Buhimschi IA, Zhao G, Baumbusch MA, Glabe CC, Buhimschi CS: Presence of misfolded soluble oligomers in urine of women with severe preeclampsia classifies preeclampsia as a protein conformational disorder. Presented at: The 29th Annual Meeting of the Society for Maternal–Fetal Medicine. San Diego, CA, USA, 26–31 January 2009 (Abstract 46).
Extended breastfeeding may protect against breast cancer
A mouse model provides support for the association between extended lactation and reduced risk of breast cancer. Researchers from Thomas Jefferson University (PA, USA) have demonstrated that the functional loss of a single gene is sufficient to confer constitutive milk production and protection against mammary tumor formation. This suggests that extended breastfeeding could be investigated as a preventative treatment against breast cancer.
The study, published in the American Journal of Pathology, adds to research indicating a significantly reduced risk of developing breast cancer in women who breastfeed for more than 2 years.
The mouse model investigated by Sotgia et al. facilitated investigation into the reason behind this association. The researchers found that mice deficient in caveolin-3 (Cav-3), a muscle-specific calveolin-related gene highly expressed in muscle and mammary gland cells, had upregulated genes associated with lactation resulting in constitutive production of milk. The mice lacking Cav-3 also demonstrated dramatic protection against mammary tumor formation after orthotopic tumor cell implantation.
“A lactation-based therapeutic strategy would provide a more natural and nontoxic approach to the development of novel anticancer therapies.”
The association between extended lactation and protection from breast cancer development in mice suggests that this model could be applied to human cancer treatment. Michael Lisanti, lead author of the study, is hopeful for a new approach to breast cancer therapy. He proposes, “A lactation-based therapeutic strategy would provide a more natural and nontoxic approach to the development of novel anticancer therapies. In this regard, targeted reduction of Cav-3 levels in the mammary gland may represent a new therapeutic strategy for preventing the onset of human breast cancers.”
Source: Sotgia F, Casimiro MC, Bonuccelli G et al.: Loss of caveolin-3 induces a lactogenic microenvironment that is protective against mammary tumor formation. Am. J. Pathol. 174(2), 613–629 (2009).
Trial suggests that weight-loss regimens may alleviate incontinence in postmenopausal women
A study carried out by researchers from the Obstetrics and Gynecology department at the University of California (CA, USA) suggests that weight-loss programs may be an effective method of treating urinary incontinence in postmenopausal women.
“…increased weight puts increased pressure on the bladder and pelvic floor, and when you raise that pressure, you have less of a margin for increased pressure … before you lose your urine.”
In the study, published in the New England Journal of Medicine, a total of 338 overweight and obese women were recruited from Providence (RI, USA) and Birmingham (AL, USA), all of whom reported a minimum of ten episodes of urinary incontinence per week. These women were assigned randomly to either a 6-month weight-loss program that involved making active changes in diet and exercise regimes or to a four-session-long educational program where the women were taught about weight loss, physical activity and healthy eating.
“…other health benefits, such as improvements in blood pressure control, sleep and libido, can also be gained from weight-loss programs…”
At the end of the 6-month period, women in the intervention program lost approximately 8% of their bodyweight (∼17 pounds each) and reported that their weekly incontinence episodes had dropped by almost half (47%). The control group reported a 1.6% loss of bodyweight (∼3 pounds) and a 28% drop in weekly incontinence episodes compared with previous levels. The decrease observed in the intervention group was more pertinent for episodes of stress incontinence, usually triggered by physical pressure on the bladder, such as during a cough, laugh or exercise.
“Our hypothesis is that increased weight puts increased pressure on the bladder and pelvic floor, and when you raise that pressure, you have less of a margin for increased pressure – through a cough, for example – before you lose your urine,” commented Leslee Subak, lead author of the study. “If you lose weight, you have less pressure on the bladder.” Subak also stresses that other health benefits, such as improvements in blood pressure control, sleep and libido, can also be gained from weight-loss programs such as these and recommends that “weight loss should be a first-line recommendation for urinary incontinence.”
Source: Subak LL, Wing R, West D et al.: Weight loss to treat urinary incontinence in overweight and obese women. N. Engl. J. Med. 360, 481–490 (2009).