Prenatal exposure to chemicals in personal care products linked to earlier puberty in girls

Association of phthalates, parabens and phenols found in personal care products with pubertal timing in girls and boys

Girls exposed to chemicals commonly found in toothpaste, makeup, soap and other personal care products before birth may hit puberty earlier, according to a new longitudinal study led by researchers at UC Berkeley (see press release).

2019 Study Abstract

STUDY QUESTION
Are in-utero or peripubertal exposures to phthalates, parabens and other phenols found in personal care products associated with timing of pubertal onset in boys and girls?

SUMMARY ANSWER
We found some associations of altered pubertal timing in girls, but little evidence in boys.

WHAT IS KNOWN ALREADY
Certain chemicals in personal care and consumer products, including low molecular weight phthalates, parabens and phenols, or their precursors, are associated with altered pubertal timing in animal studies.

STUDY DESIGN, SIZE, DURATION
Data were from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) longitudinal cohort study which followed 338 children in the Salinas Valley, California, from before birth to adolescence.

PARTICIPANTS/MATERIALS, SETTING, METHODS
Pregnant women were enrolled in 1999–2000. Mothers were mostly Latina, living below the federal poverty threshold and without a high school diploma. We measured concentrations of three phthalate metabolites (monoethyl phthalate [MEP], mono-n-butyl phthalate and mono-isobutyl phthalate), methyl and propyl paraben and four other phenols (triclosan, benzophenone-3 and 2,4- and 2,5-dichlorophenol) in urine collected from mothers during pregnancy and from children at age 9. Pubertal timing was assessed among 179 girls and 159 boys every 9 months between ages 9 and 13 using clinical Tanner staging. Accelerated failure time models were used to obtain mean shifts of pubertal timing associated with concentrations of prenatal and peripubertal biomarkers.

MAIN RESULTS AND THE ROLE OF CHANCE
In girls, we observed earlier onset of pubic hair development with prenatal urinary MEP concentrations and earlier menarche with prenatal triclosan and 2,4-dichlorophenol concentrations. Regarding peripubertal biomarkers, we observed: earlier breast development, pubic hair development and menarche with methyl paraben; earlier menarche with propyl paraben; and later pubic hair development with 2,5-dichlorophenol. In boys, we observed no associations with prenatal urinary biomarker concentrations and only one association with peripubertal concentrations: earlier genital development with propyl paraben.

LIMITATIONS, REASONS FOR CAUTION
These chemicals are quickly metabolized and one to two urinary measurements per developmental point may not accurately reflect usual exposure. Associations of peripubertal measurements with parabens may reflect reverse causality: children going through puberty early may be more likely to use personal care products. The study population was limited to Latino children of low socioeconomic status living in a farmworker community and may not be widely generalizable.

WIDER IMPLICATIONS OF THE FINDINGS
This study contributes to a growing literature that suggests that exposure to certain endocrine disrupting chemicals may impact timing of puberty in children.

STUDY FUNDING/COMPETING INTEREST(S)
This study was funded by the National Institute of Environmental Health Sciences and the US Environmental Protection Agency. The authors declare no conflicts of interest.

TRIAL REGISTRATION NUMBER
N/A.

Maternal exposure to workplace solvents may increase the risk for ASD in children

The CHARGE study : an assessment of parental occupational exposures and autism spectrum disorder

Children whose mothers are exposed to solvents at work are at higher risk of autism, shows new research.

The study found that women who are exposed to workplace solvents are 1.5 times more likely to have a child on the autistic spectrum, newnationnews reports. Image credit @ATEN_Int.

2019 Study Abstract

Objectives
The aim of this study is to determine if parental occupational exposure to 16 agents is associated with autism spectrum disorder (ASD).

Methods
Demographic, health and parental occupational data were collected as part of the CHildhood Autism Risks from Genetics and Environment (CHARGE) study. The workplace exposure assessment was conducted by two experienced industrial hygienists for the parents of 537 children with ASD and 414 typically developing (TD) children. For each job, frequency and intensity of 16 agents were assessed and both binary and semi-quantitative cumulative exposure variables were derived. Logistic regression models were used to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) to assess associations between parental occupational exposures 3 months pre-pregnancy until birth.

Results
The OR of ASD in the children of mothers exposed to any solvents was 1.5 times higher than the mothers of TD children (95% CI=1.01–2.23). Cumulative exposure indicated that the OR associated with a moderate level of solvent exposure in mothers was 1.85 (95% CI=1.09, 3.15) for children with ASD compared with TD children. No other exposures were associated with ASD in mothers, fathers or the parents combined.

Conclusion
Maternal occupational exposure to solvents may increase the risk for ASD. These results are consistent with a growing body of evidence indicating that environmental and occupational exposures may be associated with ASD. Future research should consider specific types of solvents, larger samples and/or different study designs to evaluate other exposures for potential associations with ASD.

Sex, Lies and Pharmaceuticals

The merging of marketing and medical science : female sexual dysfunction

As the search for the so-called ‘Pink Viagra’ continues, controversy surrounds the nature of the medical ‘condition’ such a pill would treat.

  • Do women with a low libido really have a disease called ‘hypoactive-sexual desire disorder’?
  • Does it really affect one-in-ten women as drug companies claim?

There’s already a marketed treatment for HSDD in the form of a pill called Addyi, a drug whose 2015 FDA approval came with intense debate over whether sexual desire was indeed a medical issue. Addyi has since become a commercial nonentity, in large part because women are restricted from drinking alcohol before taking it. The controversy around the drug’s approval faded along with its meager sales.

But bremelanotide, which promises a similar effect with fewer side effects, has rekindled the conversation around whether sexual desire can be a matter of pharmaceutical science.

Continue reading on stat news.

In an article in the BMJ almost 10 years ago I described the making of female sexual dysfunction as the freshest, clearest example of the “corporate sponsored creation of a disease.”1 Looking back over the past decade, it has become clear that drug companies have not simply sponsored the science of this new condition; on occasions they have helped to construct it. Corporate employees have worked with paid key opinion leaders to help develop the disease entity; they have run prevalence surveys to portray it as widespread; and they helped create the measurement and diagnostic instruments to persuade women that their sexual difficulties deserve a medical label and treatment. Drug marketing is merging with medical science in a fascinating and frightening way, raising questions about whether a new approach to defining diseases is warranted.

Continue reading on the BMJ.

Condition branding is a marketing technique in which companies develop conditions concurrently with developing drugs; examples include gastro-oesophageal reflux disease, premenstrual dysphoric disorder, social anxiety disorder, erectile dysfunction and hypoactive sexual desire disorder. Although it is illegal for pharmaceutical companies to market drugs prior to regulatory approval, there are no restrictions on marketing diseases, and industry seeks to establish a disease state in the minds of clinicians years before an expected drug launch. Continuing medical education (CME) courses are an important part of promotion prior to drug approval and have become a key marketing tool for increasing clinician receptivity to new products. We systematically identified 14 free, internet-based, industry-funded, accredited CME modules on hypoactive sexual desire disorder in women which came out before a new drug, flibanserin, was being considered for regulatory approval in the USA. Common themes in these modules included the following: Hypoactive sexual desire disorder is common, underdiagnosed and can have a profound effect on quality of life. Women may not be aware that they are sick or distressed. Simple questionnaires can assist clinicians in diagnosing the disorder. It is problematic that there are medicines available to treat sexual problems for men but not women. In fact, there is no scientifically established norm for sexual activity, feelings or desire, and there is no evidence that hypoactive sexual desire disorder is a medical condition. Hypoactive sexual desire disorder is a typical example of a condition that was sponsored by industry to prepare the market for a specific treatment.

Continue reading on the BMJ.

FDA bans sales of transvaginal mesh

FDA takes action to protect women’s health, orders manufacturers of surgical mesh intended for transvaginal repair of pelvic organ prolapse to stop selling all devices

April 16, 2019 – The U.S. Food and Drug Administration today ordered the manufacturers of all remaining surgical mesh products indicated for the transvaginal repair of pelvic organ prolapse (POP) to stop selling and distributing their products in the U.S. immediately. The order is the latest in a series of escalating safety actions related to protecting the health of the thousands of women each year who undergo surgery transvaginally to repair POP.

The FDA has determined that the manufacturers, Boston Scientific and Coloplast, have not demonstrated a reasonable assurance of safety and effectiveness for these devices, which is the premarket review standard that now applies to them since the agency reclassified them in class III (high risk) in 2016. As part of the 2016 reclassification, manufacturers were required to submit and obtain approval of premarket approval (PMA) applications, the agency’s most stringent device review pathway, in order to continue marketing their devices in the U.S. The companies will have 10 days to submit their plan to withdraw these products from the market.

continue reading the FDA press announcement.
Read the meshCNN press release. Image credit leakylily.

In the UK

 

Developmental Origins of Endometriosis

a Swedish cohort study, Journal of epidemiology and community health, 2019

Abstract

Background
Endometriosis is a chronic condition affecting women of reproductive age and is associated with multiple health burdens. Yet, findings regarding its ‘developmental origins’ are inconsistent. We aimed to investigate the associations of birth characteristics with endometriosis. We also explored potential mediation by adult social and reproductive factors.

Methods
This cohort study consisted of 3406 women born in Uppsala, Sweden, between 1933 and 1972. We used data from archived birth records and endometriosis diagnoses at ages 15–50 recorded in the national patient registers. Socioeconomic and reproductive characteristics were obtained from routine registers. HRs were estimated from Cox regression.

Results
During the follow-up, 111 women have been diagnosed with endometriosis, and most cases are external endometriosis (ie, outside the uterus, n=91). Lower standardised birth weight for gestational age was associated with increased rate of endometriosis (HR 1.35 per standard deviation decrease; 95% CI 1.08 to 1.67). This increased rate was also detected among women with fewer number of live births (HR 2.38; 95% CI 1.40 to 4.07 for one child vs ≥2 children; HR 6.09; 95% CI 3.88 to 9.57 for no child vs ≥2 children) and diagnosed infertility problem (HR 2.00; 95% CI 1.10 to 3.61) prior to endometriosis diagnosis. All the observed associations were stronger for external endometriosis. However, no evidence was found that number of births was the mediator of the inverse association between standardised birth weight and endometriosis.

Conclusion
This study supports the developmental origins theory and suggests that exposure to growth restriction during the fetal period is associated with increased risk of endometriosis during reproductive years.
Image credit hellomagazine.

DES Exposure and Endometriosis

Vulvar Cancer is on the Rise in the UK, study shows

Relationship between vulvar symptoms and incidence of vulvar cancer in women referred to a rapid access clinic

Abstract

Objective
We performed a study to estimate incidence of vulvar cancer in women with vulvar symptoms (irritation, pain, bleeding +/− presence of lesion) referred to a secondary care, rapid‐access clinic.

Methods
Prospective data collection of all direct referrals from a primary to a secondary care gynecological oncology clinic from 2011 to 2016, for women with suspicious vulvar symptoms.

Results
32/393 (8.1%) women had vulvar cancer, and 24/393 (6.1%) had a premalignant lesion. Multivariate logistic regression showed that women referred without a specific lesion had considerably lower odds of a diagnosis of vulvar cancer than those with a lesion (OR=0.11, 95% CI: 0.03–0.49). In total, 30/234 (12.8%) women with a vulvar lesion (mass or ulcer), had vulvar cancer, compared with 2/159 (1.3%) of those referred without a lesion (these patients had vulvar irritation and bleeding but had a visible lesion on examination). None of the 140 women with irritation alone, in the absence of a visible lesion or bleeding, had pre‐invasive disease or cancer.

Conclusion
Presence of a vulvar lesion, especially if painful/bleeding, has a high positive predictive value for vulvar cancer and 12.8% of women presenting with any vulvar lesion to secondary care had cancer.

Discussion

Overall, 32/393 (8.1%) women referred with vulvar symptoms were diagnosed with a malignancy and a further 24/393 (6.1%) were diagnosed with a pre‐malignant lesion. The presence of a suspicious vulvar lesion, especially if symptomatic, was associated with a cancer diagnosis in 30/234 (12.8%) women. Unless the lesion is obviously benign (which in this series included: sebaceous inclusion cyst; urethral caruncle; inspissated sebaceous material trapped under the clitoral hood; and ecchymosis on a background of lichen sclerosus), a rapid‐access clinic referral is appropriate to exclude a malignancy in these women. A larger cohort would be required to stratify risk by age. However, as the incidence of vulvar cancer is increasing, especially in younger women, it would be important not to dismiss suspicious symptoms based on age alone.

Women without a visible lesion were extremely unlikely to have cancer, based on this cohort of patients (<1.3% depending on whether presence of lesion was defined by patient/primary care [0/159] vs secondary care (2/159). However, these findings would need to be applied to a larger population to test this hypothesis and with wider generalization to other healthcare populations. One strength of this dataset is that the population is well‐defined and relatively stable, so re‐referrals, subsequently diagnosed with a cancer, would have been referred back to the same clinic. In the present series, six women were re‐referred during the study period (one woman was seen three times and five women were seen twice). None of these women had a cancer diagnosis. Unfortunately, we were not able to define an average lead time from onset of symptoms to diagnosis from our data, since this was not reliably recorded.

Many women with symptoms of vulvar soreness and irritation, in the absence of a specific lesion, were diagnosed with an inflammatory condition; half had lichen sclerosus or lichen planus. Primary care physicians should be reassured that, in the absence of a suspicious lesion, a cancer diagnosis or a pre‐malignant condition was unlikely. As per dermatology guidelines, if there are classical signs of lichen sclerosis, a diagnostic biopsy is not needed if there is a response to high‐potency topical steroids. Women whose symptoms do not start to improve after 2–3 weeks of treatment, should be re‐assessed and referred if symptoms persist or a lesion develops.

The overall incidence of vulvar cancer in this series was slightly lower than in those in the literature. This is perhaps surprising, as the local population is relatively elderly; in the 2011 census 29.1% of West Somerset were aged 65 years or over compared with a UK average of 16.4%. However, this series is nearly 10‐fold larger than those previously published, so may reflect the increased statistical power of this study. It may also reflect a difference in local referral patterns and criteria, since women may be referred to a general gynecology clinic or a dermatologist in other areas. One study from an urban area in the South East of England looked at cancer diagnosis rates in women referred to a gynecologic fast‐track clinic. They included a total of 335 women referred to secondary care. Only 18 women had symptoms suggestive of vulvar cancer, of whom only two (11.1%) were diagnosed with vulvar cancer. A similar study, also from the South East of England, included only 13 women with vulvar symptoms and found a positive predictive value of a cancer diagnosis of 15.4% in this subset. A further series of women with suspected gynecologic malignancy, also from the South East of England, included 1105 women referred to secondary care. Forty‐four of these women were referred with suspected vulvo‐vaginal cancer and 13.6% were diagnosed with a malignancy.

These data help to differentiate between those who should be referred via a fast‐track clinic and those who could be treated more conservatively for vulvar symptoms, and could help to inform national guidance—including future updates of NICE guidelines. Further data would be required to determine whether these data had wider applicability in other, more diverse populations, and these data are limited by the secondary care focus of this study. It would be interesting to compare rates of women presenting with vulvar symptoms in a primary care population with secondary care referrals and cancer incidence in that population over the same time period to provide evidence for triage of those requiring rapid assessment. This is important in the face of the increasing incidence of vulvar cancer, due to changes in demographics and HPV prevalence.

Finally, many women delay presentation and may have significant symptoms for many months, due to fear, embarrassment or lack of awareness of vulvar conditions generally, and vulvar cancer in particular. Many women in our series had inappropriate treatment for vulvar skin conditions or suspicious lesions with low potency steroids, topical estrogens, anti‐fungal agents, antibiotics, or no treatment at all for prolonged periods. This may be due to ‘home remedy’ self‐treatment (possibly fueled by lack of knowledge and advertisements for ‘intimate itching’), avoidance of doctors, or reluctance to use adequate courses of high potency topical steroids, by both physicians and the women affected. Research is also needed to inform us about barriers to presentation, especially in older women, who are most at risk of vulvar cancers, and to improve health education for this under‐resourced area.
Feature image credit @DiggerGraham (see below).

The 30-year fight for breast implant safety

Breast implants are 60 years old, and we are still fighting about whether they are safe or not

Sybil Goldrich and Jamee Cook both suffered after getting breast implants, Sybil in 1983 and Jamee in 1998. Together, they are fighting regulators to get more information to people considering getting breast implants.

ICIJfights corruption with the world’s best cross-border watchdog journalism by over 160 investigative reporters in 60+ countries. The home of Offshore Leaks.”

L’agence du médicament retire du marché des implants mammaires

L’ANSM rappelle sa recommandation d’utiliser de préférence des implants mammaires lisses en chirurgie esthétique ou reconstructrice

Communiqué ANSM

Depuis l’apparition en 2011 des premiers cas de lymphomes anaplasiques à grandes cellules associés aux implants mammaires (LAGC-AIM), l’Agence nationale du médicament et des produits de santé (ANSM) a mené de nombreuses investigations afin d’étudier le lien entre la survenue de cas de LAGC et la texture des implants mammaires.

Au regard de l’ensemble des informations dont elle dispose, dont des avis d’experts indépendants, l’ANSM considère que la texturation de certains implants macrotexturés et implants à surface recouverte de polyuréthane constitue un facteur de risque dans l’apparition de LAGC-AIM.

Ainsi, l’ANSM prend la décision, par mesure de précaution, de retirer du marché ces implants afin de réduire l’exposition des femmes au risque de LAGC qui reste un risque rare mais grave.Compte tenu de la rareté de ce risque, l’ANSM ne recommande pas d’explantation préventive pour les femmes porteuses de ces implants.

L’ANSM met en place le numéro vert 0.800.71.02.35 pour répondre aux interrogations des patientes. Celles-ci sont également invitées à consulter un professionnel de santé en cas de questions complémentaires.

Compte tenu de la rareté du risque de survenue de LAGC-AIM et de l’avis du CSST, l’ANSM ne recommande pas d’explantation préventive des implants macrotexturés et des implants à surface recouverte de polyuréthane.

Liste des implants mammaires concernés par la décision de l’ANSM

En Savoir Plus

Primodos Drug Cover-Up : Yasmin Qureshi MP Talks, 2017

Yasmin Qureshi explains one possible reason for the Primodos cover-up

Yasmin Qureshi MP gives one reason Primodos drug problems that potentially deformed and killed babies might have been covered up.

More information

40 years after exposure, Pesticide linked to higher breast cancer risk

DDT and Breast Cancer: Prospective Study of Induction Time and Susceptibility Windows

According to a recent study, DDT exposure before puberty may have increased the breast cancer risk for women in their 50s. Study is the latest to suggest early-life exposures, even prior to birth, may hold the key to understanding who gets diseases, Environmental Health News reports.

2019 Study Abstract

Background
In a previous Child Health and Development Studies report, p, p’-DDT was associated with a fivefold increased risk of premenopausal (before age 50 years) breast cancer for women first exposed before puberty. Here we extend our observation to breast cancer diagnosed during early postmenopause (ages 50–54 years) to determine whether age at diagnosis modifies the interaction of DDT with age at exposure.

Methods
We conducted a second prospective, nested case-control study in the Child Health and Development Studies (153 incident breast cancer cases diagnosed at ages 50–54 years and 432 controls matched to cases on birth year). These were analyzed separately and pooled with our previous study (129 breast cancer cases diagnosed at ages 31–49 years and 129 controls matched on birth year). Blood samples were obtained during pregnancy (median age, 26 years), 1–3 days after delivery from 1959 to 1967 in Oakland, California. Serum was assayed for p, p’-DDT, o, p’-DDT, and p, p’-DDE. Odds ratios (ORs) below are given for doubling of serum p, p’-DDT. All statistical tests were two-sided.

Results
For early postmenopausal breast cancer, p, p’-DDT was associated with risk for all women (ORDDT 50–54 = 1.99, 95% CI = 1.48 to 2.67). This association was accounted for by women first exposed to DDT after infancy (ORDDT 50–54 for first exposure after infancy = 2.83, 95% CI = 1.96 to 4.10 vs ORDDT 50–54 for first exposure during infancy = 0.56, 95% CI = 0.26 to 1.19; Pinteraction DDT x age at first exposure = .01). In contrast, for premenopausal breast cancer, p, p’-DDT was associated with risk among women first exposed during infancy through puberty, but not after (ORDDT<50 for first exposure during infancy = 3.70, 95% CI = 1.22 to 11.26, Pinteraction DDT x age at first exposure x age at diagnosis = .03).

Conclusions
p, p’-DDT was associated with breast cancer through age 54 years. Risk depended on timing of first exposure and diagnosis age, suggesting susceptibility windows and an induction period beginning in early life. DDT appears to be an endocrine disruptor with responsive breast targets from in utero to menopause.