The Non-Monotonic Dose Response to Endocrinology

The endocrine system is not linear, it doesn't respond linearly. Plastics were considered miracles of modern science. And they allowed us to have the lifestyle that we wanted. The production of plastic increased phenomenally rapidly after about, at the end of the war.

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In this episode you will uncover the pressing effects of declining fertility rates on the human population, delve into the influence of environmental factors, specifically exposure to harmful chemicals, on reproductive health, gain insights on age, egg/sperm quality, and environmental influences in fertility, grasp the effects of phthalates on male reproductive health, highlighting AGD and sperm count, and also realize the importance of increased awareness, research, and action to safeguard human health and fertility.

Dr. Shanna Swan is an Environmental and Reproductive Epidemiologist. She is Professor of Environmental Medicine and Public Health at the Icahn School of Medicine at Mount Sinai, New York, Adjunct Professor in Obstetrics and Gynecology at the University of California San Francisco and Senior Scientist at Environmental Health Sciences. Dr. Swan's work examines the impact of environmental exposures on reproductive health and neurodevelopment.

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Episode Overview

00:07:32 - Population Decline,
The world's fertility rate has dropped from over five children per couple to under two now, and a large proportion of the world is now below replacement.

00:12:17 - The Roller Coaster of Fertility,
The declining fertility rate in many countries means that we are headed towards a maximum world population, which will decrease and never come back.

00:15:37 - Social Causes of Fertility Decline,
The decline in fertility is not just due to social causes like women entering the workforce and getting educated, but also due to environmental and lifestyle factors.

00:22:28 - Environmental and Lifestyle Factors Affecting Fertility,
Environmental and lifestyle factors, such as exposure to phthalates and Bisphenol A, are major contributors to the decline in fertility.

00:16:51 - The Challenges of Motherhood and Fertility,
Dr. Stephanie and Dr. Shanna discuss the challenges of motherhood and fertility. The decline in egg quality and sperm quality with age is a major limiting factor in infertility, which is a concern for women who choose to have babies later in life.

00:19:57 - Decline in Male Fertility,
Dr. Shanna explains that research on the declining rate of male fertility has been around for 30 years. The first study in 1992 reported that sperm count had decreased by 50% in 50 years. However, this figure was met with skepticism.

00:23:30 - Early Puberty in Girls,
Dr. Stephanie brings up the phenomenon of early puberty in girls, and Dr. Shanna explains that it is a real concern. Girls are starting menstruation earlier and earlier, which is not only a risk for psychological and social challenges but also for fertility.

00:25:46 - Environmental Factors Affecting Sperm Count,
Dr. Shanna discusses her study on environmental factors affecting sperm count. She found that exposure to phthalates, a chemical found in plastics, is linked to lower sperm count. Exposure to other chemicals like bis

00:34:10 - Factors Affecting Sperm Count,
The recruitment bias and selection bias of the men in the studies from 1940 and 1990 were analyzed. The lifestyle factors of smoking, obesity, exercise, and stress were found to be important. Chemicals that affect the reproductive system, particularly testosterone and estrogen, were also identified.

00:40:16 - Plastic Increase and Endocrine-Disrupting Chemicals,
After World War II, scientists were revered, and plastic production increased rapidly. However, plastic has a large number of chemicals that can alter hormones. Phthalates are particularly concerning as they lower testosterone levels and can affect genital formation during pregnancy.

00:43:45 - Non-Monotonic Dose Response and Endocrinology,
Hormones often respond non-linearly to low doses of chemicals, affecting not just testosterone, but also estrogen and the immune system. Endocrine-disrupting chemicals can have a significant effect, regardless of the dose.

00:49:57 - Phthalate Syndrome,
Phthalates can cause the phthalate syndrome, where exposure in utero in male rodents can affect genital formation and induce infertility and other health problems. Humans have phthalates in their bodies, and pregnant women are particularly at risk for exposure.

00:51:44 - Development of Genitalia in Male and Female Fetuses,
Dr. Swan explains how the genitals of fetuses develop under genetic regulation, and everything changes during a critical period of gestation. She highlights how testosterone contributes to the differentiation of genitalia in male fetuses and explains how insufficient testosterone exposure can undermasculinize males.

00:54:27 - The Analogeneital Distance (AGD),
Dr. Estima and Dr. Swan discuss the AGD and how it is an important distance that differentiates males and females in almost every mammal. They also discuss how it can be difficult to measure the AGD accurately because it is soft tissue and how standardization of the position of the legs is necessary when measuring the AGD.

01:02:36 - The Phthalate Syndrome in Humans,
Dr. Swan discusses how she found the phthalate syndrome in humans after researching variations in AGD, penile size, and descent of the testicles. She highlights how many papers have found other chemicals related to AGD and how she would love to see AGD become part of the standard of care.

01:05:14 - Implications of AGD on Testosterone and Longevity,
Dr. Swan explains how AGD has massive implications on men's capacity for testosterone, sperm production, and longevity.

01:08:09 - The Relationship between AGD and Sperm Count,
Dr. Swan discusses her research on the relationship between AGD (anogenital distance) and sperm count. Her study found a direct linear relationship between the length of AGD and the number of sperm, indicating that the longer the AGD, the higher the sperm count.

01:13:27 - Phthalate Syndrome and Exposure,
Dr. Swan explains phthalate syndrome, a condition assigned at birth that affects the male reproductive system and is caused by exposure to phthalates. She discusses the common sources of phthalates, such as plastic tubing, personal care products, and food packaging.

01:15:24 - NICU Exposure and Other Hormonal Effects,
Dr. Swan highlights the dangers of exposure to phthalates and other hormone-disrupting chemicals in the NICU, where preemies are especially vulnerable. She also notes that these chemicals can affect other hormonal systems in the body, such as lung development, brain development, and blood pressure.

01:20:28 - BPA-Free Products and Other Chemicals,
Dr. Swan addresses the issue of manufacturers substituting BPA-free products with similar chemicals that have the same effects. She also mentions other chemicals that disrupt hormones, such as PFAS chemicals in Teflon and sunscreen.

01:26:10 - Gender Dysphoria and Environmental Chemicals,
Dr. Swan explores the relationship between gender dysphoria and exposure to environmental chemicals. She acknowledges the complexity of the topic and emphasizes the need for further research before drawing conclusions.