Noresthisterone period delay pill now sold over the counter : is it safe ?

What will be the real cost of “giving women more choices” and messing with their bodies” ?

“The Period Delay Pill has been available on our Online Doctor service previously and now introducing it in our pharmacies and nurse clinics with a consultation and questionnaire allows women to make the choice easily and quickly should they choose to delay their period.”

Michael Henry, healthcare director for Superdrug.

Reported Side Effects

Asthma; cardiac dysfunction; conditions that may worsen with fluid retention; diabetes (progestogens can decrease glucose tolerance—monitor patient closely); epilepsy; history of depression; hypertension; migraine; susceptibility to thromboembolism (particular caution with high dose).

When used for contraception

Active trophoblastic disease (until return to normal of urine- and plasma-gonadotrophin concentration)—seek specialist advice; arterial disease; functional ovarian cysts; history of jaundice in pregnancy; malabsorption syndromes; past ectopic pregnancy; sex-steroid dependent cancer; systemic lupus erythematosus with positive (or unknown) anti-phospholipid antibodies with intramuscular use for contraception disturbances of lipid metabolism; history during pregnancy of deterioration of otosclerosis; history during pregnancy of pruritus; possible risk of breast cancer.

Cautions, further information

A possible small increase in the risk of breast cancer should be weighed against the benefits.

The product literature advises caution in patients with history of thromboembolism, hypertension, diabetes mellitus and migraine; evidence for caution in these conditions is unsatisfactory.

Read NICE guidelines about norethisterone.

“Like the contraceptive pill, period delay pills are not side-effect free. Norethisterone is a synthetic version of the naturally occurring hormone progesterone and, like the other synthetic hormones in contraception, it can cause breast tenderness, nausea, headaches, low libido and, crucially, ‘disturbances in mood’. What the NHS likely means by this is mental health side effects which can range from ‘feeling a bit low’ to full-blown depression and anxiety. No two women are the same and so no two women will respond to a pill in the same way.”

Read Why no one’s talking about the worrying side effects of period delay tablets on Metro, 10 Aug 2019.

T-shaped uterus and subtle uterine variances

A need for reliable criteria, Fertility and Sterility, August 2019

Abstract

The ASRM Class VII, the ESHRE/ESGE Class U1, and the T-shaped uterus have a uniquely interesting history. The T-shaped uterus was first described as a diethylstilbestrol– (DES-) related congenital uterine anomaly based on findings from hysterosalpingography by Kaufman in 1977. Together with two similar morphologic forms of the uterus—constricting bands in the uterine cavity and a widening of the lower two-thirds of the uterus—this was included as a separate class of DES-related anomalies by the Buttram and Gibbons 1979 classification, and its further modification—the American Fertility Society classification.

In 2013, ESHRE/ESGE singled out a subtle uterine variance with a thickened lateral wall and a T-shaped uterus. As a result, the diagnosis of subtle uterine variances has increased with the designation of a T-shaped uterus or dysmorphic uterus and surgical repair is offered to enhance fertility. However, there is insufficient evidence to offer it in daily practice even in women with recurrent pregnancy loss, where historically metroplasty of the T-shaped uterus is rarely reported and its surgical correction is always questionable.

In this issue Alonso Pacheco et al. present a nicely done video using three-dimensional ultrasound and hysteroscopy in three cases of what they believe is a T-shaped uterus that is representative in distinguishing three of its subclasses. The authors used three-dimensional ultrasound and hysteroscopy to suggest that T-shaped uterus can be subclassified as T-shaped, Y-shaped, or I-shaped uterus. However, the division still remains arbitrary based on subjective impression of the presence of thickened wall and letter-shaped uterine cavities in these conditions. Discussion.

Bisphenol-A can promote fibroids growth, study says

Bisphenol A promotes the proliferation of leiomyoma cells by GPR30‐EGFR signaling pathway, 2019

Abstract

Aim
To study the molecular mechanism of G protein‐coupled receptor 30‐epidermal growth factor receptor (GPR30‐EGFR) signaling pathway on the proliferation of leiomyoma cells exposed with bisphenol A.

Methods
Primary cultures and subcultures of human uterine leiomyoma (UL) cells. The expressions of messenger RNA and proteins of GPR30 and EGFR in 15 leiomyoma tissue specimens and all groups were detected by real‐time quantitative polymerase chain reaction assay and Western blot assay. The protein of mitogen‐activated protein kinases (MAPK)/extracellular signal–regulated kinases (ERK)/c‐fos signaling pathway members was detected by Western blot assay.

Results
Bisphenol A promoted the growth of UL cells and the expressions of GPR30, EGFR, c‐fos and p‐ERK1/2.

Conclusion
Bisphenol A was found to be a promoter specifically to proliferate the human UL cells by activating the transcription and translation of GPR30‐EGFR and MAPK/ERK/c‐fos signaling pathway members.

Pause on the use of vaginally inserted surgical mesh for stress urinary incontinence

The UK government and NHS have accepted the recommendation from the Independent Medicines and Medical Devices Safety Review, 17 July 2018

Following their acceptance of the recommendation from the Independent Medicines and Medical Devices Safety Review, the government and NHS have paused the use of vaginally inserted surgical mesh for stress urinary incontinence until a set of conditions to ensure that patients receive safe and high-quality care are met. This pause has been extended to include vaginally inserted surgical mesh for pelvic organ prolapse and will be implemented through a high vigilance programme of restricted practice.

These procedures have not been banned and during this pause, they will continue to be used when there is no viable alternative and after close and comprehensive consultation between patient and clinician.

There has not been any new evidence which would prompt regulatory action and the position of MHRA remains the same on these medical devices. We continue to work with other regulators in the EU and wider, as well as colleagues across the health sector, to monitor and examine evidence as it becomes available.

continue reading the GOV.UK News story, 17 July 2018.

Related

Evidence that intrauterine exposure to oral contraceptives might slightly affect pubertal timing

Pubertal development after unintended intrauterine exposure to oral contraceptives: a nationwide cohort study

2019 Study Abstract

Objective
To study the associations between exposure to oral contraceptives before conception and early in pregnancy and pubertal timing in boys and girls.

Design
Population-based cohort study.

Setting
Not applicable.

Patient(s)
Overall, 15,800 children (70%) born during 2000–2003 into the Danish National Birth Cohort were categorized according to maternal use of combined oral contraceptive pills or progestin-only pills reported around gestational week 17: no exposure (reference), exposure 4 months before conception, and exposure in early pregnancy. Children self-assessed pubertal status using Web-based questionnaires from 11 years and biannually throughout puberty.

Intervention(s)
None.

Main Outcome Measure(s)
Adjusted mean age differences (months) for attaining individual pubertal milestones and overall pubertal timing. Proportion mediated by prepubertal body mass index.

Result(s)

  • In boys, intrauterine exposure to oral contraceptives showed a tendency toward slightly earlier mean age for voice break (months, −3.8; 95% confidence interval [CI] −6.5, −1.0) and first ejaculation (months, −2.9; 95% CI −5.9, 0.1) and a mean difference of −1.4 months (95% CI −3.3, 0.4) for overall pubertal timing.
  • Girls with intrauterine exposure tended to have slightly earlier age at menarche (months, −1.9; 95% CI −4.0, 0.3) and Tanner breast stages and had a mean difference of −0.9 months (95% CI −2.7, 1.0) for overall pubertal timing.
  • Exposure before conception was not associated with pubertal timing. Prepubertal body mass index did not play a mediating role.

Conclusion(s)
This study shows some evidence that intrauterine exposure to oral contraceptives might slightly affect pubertal timing.

FDA requests Allergan to recall certain breast implants and tissue expanders from market

Allergan Voluntarily Recalls BIOCELL® Textured Breast Implants and Tissue Expanders, 07.24.2019

“The U.S. Food and Drug Administration today took significant action to protect women from breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) by requesting that Allergan, the manufacturer of a specific type of textured implant, recall specific models of its textured breast implants from the U.S. market due to the risk of BIA-ALCL. Following the agency’s request, Allergan has notified the FDA that it is moving forward with a worldwide recall of their BIOCELL textured breast implant products, including: Natrelle Saline-Filled breast implants, Natrelle Silicone-Filled breast implants, Natrelle Inspira Silicone-Filled breast implants, and Natrelle 410 Highly Cohesive Anatomically Shaped Silicone-Filled breast implants. The recall also includes tissue expanders used by patients prior to breast augmentation or reconstruction, including Natrelle 133 Plus Tissue Expander and Natrelle 133 Tissue Expander with Suture Tabs. The recall helps ensure that unused products are removed from suppliers and doctors’ offices. The agency also issued a safety communication today for patients with breast implants, patients considering breast implants and their health care professionals outlining the known risks and what steps patients should consider when monitoring for symptoms of BIA-ALCL, including swelling and pain in their breasts. The safety communication also lists information about all models and style numbers included in the recall.” …

continue reading The FDA Takes Action to Protect Patients from Risk of Certain Textured Breast Implants; Requests Allergan Voluntarily Recall Certain Breast Implants and Tissue Expanders from the Market: FDA Safety Communication, 25/07/2019.

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