Tag: progesterone

Categories : Obstetrics & Gynaecology Pain ManagementTags : Leave a comment

Oestrogen and Progesterone Stimulate the Body to Make Opioids

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Source: Pixabay CC0

Female hormones can suppress pain by making immune cells near the spinal cord produce opioids, a new study from researchers at UC San Francisco has found. This stops pain signals before they get to the brain.

The discovery could help with developing new treatments for chronic pain. It may explain why some painkillers work better for women than men and why postmenopausal women, whose bodies produce less of the key hormones oestrogen and progesterone, experience more pain.

The work reveals an entirely new role for T regulatory immune cells (T-regs), which are known for their ability to reduce inflammation.

“The fact that there’s a sex-dependent influence on these cells – driven by oestrogen and progesterone – and that it’s not related at all to any immune function is very unusual,” said Elora Midavaine, PhD, a postdoctoral fellow and first author of the study, which appears in Science.

The researchers looked at T-regs in the protective layers that encase the brain and spinal cord in mice. Until now, scientists thought these tissue layers, called the meninges, only served to protect the central nervous system and eliminate waste. T-regs were only discovered there in recent years.

“What we are showing now is that the immune system actually uses the meninges to communicate with distant neurons that detect sensation on the skin,” said Sakeen Kashem, MD, PhD, an assistant professor of dermatology. “This is something we hadn’t known before.”

That communication begins when a neuron, often near the skin, receives a stimulus and sends a signal to the spinal cord.

The team found that the meninges surrounding the lower part of the spinal cord harbour an abundance of T-regs. To learn what their function was, the researchers knocked the cells out with a toxin.

The effect was striking: Without the T-regs, female mice became more sensitive to pain, while male mice did not. This sex-specific difference suggested that female mice rely more on T-regs to manage pain.

“It was both fascinating and puzzling,” said Kashem, who co-led the study with Allan Basbaum, PhD. “It actually made me sceptical initially.”

Further experiments revealed a relationship between T-regs and female hormones that no one had seen before: Estrogen and progesterone were prompting the cells to churn out enkephalin, a naturally occurring opioid.

Exactly how the hormones do this is a question the team hopes to answer in a future study. But even without that understanding, the awareness of this sex-dependent pathway is likely to lead to much-needed new approaches for treating pain.

In the short run, it may help physicians choose medications that could be more effective for a patient, depending on their sex. Certain migraine treatments, for example, are known to work better on women than men.

This could be particularly helpful for women who have gone through menopause and no longer produce oestrogen and progesterone, many of whom experience chronic pain.

The researchers have begun looking into the possibility of engineering T-regs to produce enkephalin on a constant basis in both men and women.

Source: University of California – San Francisco

Categories : Gender Immune SystemTags :

Male and Female Immune Systems are Trained Differently

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Scanning electron micrograph of a B cell. Credit: NIH

When the immune system is compromised due to various conditions and medicines, patients can experience opportunistic infection. Now, researchers reporting in Cell Reports have uncovered a sex-based variance in the trained immune memory response to infection in mice that might translate to humans.

The researchers, from the University of Missouri School of Medicine, found that female mice were more vulnerable to opportunistic infection from a bacterial pathogen to which they had previously been exposed when progesterone levels were naturally elevated as part of their reproductive cycle.

“Differences in immune response in males and females have been observed before. For instance, males had increased morbidity and severity of COVID-19 from SARS-CoV-2 infections,” said Dr Adam Schrum, associate professor in the Department of Molecular Microbiology and Immunology. “But females are known to suffer other infections worse than males. Our research found that female mice were far more vulnerable to opportunistic bacterial infection than male mice because of a sex-based difference in their trained immunity.”

To understand why the immune systems of female and male mice responded differently to a bacterial pathogen, the researchers examined whether the reproductive cycle affected immune training. They found that elevated progesterone levels correlated with lower trained immune responses. To test this more fully, the researchers gave the female mice progesterone blockers and found that their trained immune response was subsequently enhanced.

“The female mice had significantly restored trained immune response when progesterone was blocked, reaching comparable levels to those of male mice,” said Schrum. “Sex hormone-based modulation of immune function needs more study to be fully understood, but as a first step we can conclude that immune training is influenced by a progesterone-dependent mechanism that results in a sex bias in mice.”

In addition to further study to understand how and why progesterone specifically influences trained immune responses in mice, the researchers pointed out that because mice have shorter estrous cycles than the human menstrual cycle, further research is needed to understand how sex hormones might affect human immune training.

Source: University of Missouri-Columbia

Categories : Mental Health Obstetrics & GynaecologyTags :

New Study Finds Depression Risk with Hormonal Contraceptive Use

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The possibility that contraceptive pills might have negative effects on mental health and even lead to depression has long been debated. Now, evidence published in Epidemiology and Psychiatric Sciences shows that contraceptive pills are in fact linked to depression, with teenage girls at particularly increased risk.

This study is one of the largest and widest-ranging to date, following more than a quarter of a million women from UK Biobank from birth to menopause.

The researchers collected data about women’s use of contraceptive pills, the time at which they were first diagnosed with depression and when they first experienced symptoms of depression without receiving a diagnosis. The method of contraception studied was combined contraceptive pills, which contain progestogen and oestrogen. Progestogen prevents ovulation and thickens the cervical mucus to prevent sperms from entering the uterus, while oestrogen thins the uterine lining to hinder the implantation of a fertilised egg.

“Although contraception has many advantages for women, both medical practitioners and patients should be informed about the side-effects identified in this and previous research,” says Therese Johansson at Uppsala University, one of the researchers leading the study.

According to the study, women who began to use contraceptive pills as teenagers had a 130% higher incidence of symptoms of depression, while the corresponding increase among adult users was 92%.

“The powerful influence of contraceptive pills on teenagers can be ascribed to the hormonal changes caused by puberty. As women in that age group have already experienced substantial hormonal changes, they can be more receptive not only to hormonal changes but also to other life experiences,” Johansson says.

The researchers were also able to see that the increased incidence of depression declined when the women continued to use contraceptive pills after the first two years. However, teenage users of contraceptive pills still had an increased incidence of depression even after stopping using the pill, which was not observed in adult users of contraceptive pills.

“It is important to emphasise that most women tolerate external hormones well, without experiencing negative effects on their mood, so combined contraceptive pills are an excellent option for many women. Contraceptive pills enable women to avoid unplanned pregnancies and they can also prevent illnesses that affect women, including ovarian cancer and uterine cancer. However, certain women may have an increased risk of depression after starting to use contraceptive pills.”

The findings of the study point to a need for healthcare professionals to be more aware of possible links between different systems in the body, such as depression and the use of contraceptive pills. The researchers conclude that it is important for care providers to inform women who are considering using contraceptive pills of the potential risk of depression as a side-effect of the medicine.

“Since we only investigated combined contraceptive pills in this study, we cannot draw conclusions about other contraceptive options, such as mini pills, contraceptive patches, hormonal spirals, vaginal rings or contraceptive rods. In a future study, we plan to examine different formulations and methods of administration. Our ambition in comparing different contraceptive methods is to give women even more information to help them take well-informed decisions about their contraceptive options,” Johansson says.

Source: Uppsala University

Categories : Cancer Obstetrics & GynaecologyTags :

Synthetic Progestogen in Utero Leads to Doubled Cancer Rate in Offspring

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Photo by Shvets Productions on Pexels

In utero exposure to a synthetic progestogen used to prevent miscarriage can lead to an increased risk of developing cancer, according to a new study.

The study by researchers at The University of Texas Health Science Center at Houston (UTHealth Houston) was published in the American Journal of Obstetrics and Gynecology.

The drug, 17α-hydroxyprogesterone caproate (17-OHPC), is a synthetic progestogen frequently used by women in the 1950s and 1960s, and is still prescribed today to women to help prevent preterm birth. Progesterone helps the uterus grow during pregnancy and prevents early contractions that may lead to miscarriage.

“Children who were born to women who received the drug during pregnancy have double the rate of cancer across their lifetime compared to children born to women who did not take this drug,” said the study’s lead author, Caitlin C. Murphy, PhD, MPH, associate professor in the Department of Health Promotion and Behavioral Sciences at UTHealth School of Public Health in Houston. “We have seen cancers like colorectal cancer, pancreatic cancer, thyroid cancer, and many others increasing in people born in and after the 1960s, and no one really knows why.”

Researchers reviewed data from the Kaiser Foundation Health Plan on women who received prenatal care between June 1959 and June 1967, and the California Cancer Registry, which traced cancer in offspring through 2019.

Out of more than 18 751 live births, researchers discovered 1008 cancer diagnoses were made in offspring ages 0 to 58 years. Additionally, a total of 234 offspring were exposed to 17-OHPC during pregnancy. Offspring exposed in utero had cancer detected in adulthood at more than twice the rate of of those unexposed: 65% of cancers occurred in adults younger than 50.

“Our findings suggest taking this drug during pregnancy can disrupt early development, which may increase risk of cancer decades later,” Murphy said “With this drug, we are seeing the effects of a synthetic hormone. Things that happened to us in the womb, or exposures in utero, are important risk factors for developing cancer many decades after we’re born.”

A new randomised trial shows there is no benefit of taking 17-OHPC, and that it does not reduce the risk of preterm birth, according to Murphy.

The U.S. Food and Drug Administration proposed in October 2020 that this particular drug be withdrawn from the market.

Source: University of Texas Health Science Center at Houston