Coming Soon... Children of Men? NewsWire

NewsWire: 3/8/21

• In her new book Count Down, epidemiologist Shanna H. Swan warns of a coming crisis in reproductive health. The book argues that endocrine-disrupting chemicals in our environment are wreaking havoc on sperm counts and egg quality and are weakening the ability of humankind to reproduce. (The New York Times)
• NH: Why is fertility falling around the world? Ask a demographer, or indeed any social scientist, and they will give you plenty of plausible explanations. I discuss them often in the NewsWire: everything from spreading affluence, urbanization, education, and secularization to the rising economic cost of raising children and the declining economic rewards they provide to parents as they grow up.
• These are good enough stories as far as they go. But if you ask experts in the biological sciences nowadays, there is a growing likelihood they will give you a very different kind of explanation.
• Societies are having fewer children, many say, because people are physiologically changing in way way that makes them less capable of having children and maybe even less interested in sexual activity at all. The changes are likely triggered by environmental chemicals called EDCs (more on that below). What's more, they worry that the changes are associated with a rising incidence in chronic health disorders that also threaten quality of life and life expectancy.
• Leading these biology-based worriers is Dr. Shanna Swan, a well-published epidemiologist and biostatistician who teaches at Mount Sinai Hospital. Back in 2017 she coauthored a meta-analysis of 185 studies of sperm counts from 1973 to 2011 in North America, Europe, and Australia. Over 43K men were covered. Conclusion: Over those 38 years, after controlling for health and lifestyle, age-adjusted sperm counts were down 52% "with no evidence of levelling off in recent years." That's a steady decline of well over one percent per year.
• See the following bottom-line trends. "West" means only North America, Europe, and Australia. "Unselected" means total population, not selected according to fertility status.

• Major news outlets picked up on the story. Newsweek ran an August 2017 cover story titled "Who's Killing America's Sperm?" Fertility clinic doctors testified on how sperm were not just declining in quantity, but also in "motility and morphology." A surprised public learned that the WHO has been steadily lowering the threshold for what is considered an "adequate" sperm count. Back in the 1940s, 60 million/mL was considered a good lower bar, prompting WHO to set adequacy at a generous 40 million/mL. But in 1980 it lowered the threshold to 20. And then in 2010 it lowered it again to 15.
• This winter, Swan published a book, Count Down. Her thesis is summed up in her grim subtitle: "How Our Modern World Is Threatening Sperm Counts, Altering Male and Female Reproductive Development, and Imperiling the Future of the Human Race."
• I have covered similar findings in recent years. See, for example, "You're Not the Man Your Father Was," in which I reported on the growing evidence that serum testosterone levels in men have been falling across successive birth cohorts born since the 1930s. The rate of decline, about one percent per year, is similar to the decline in sperm counts. This is hardly surprising, since testosterone and sperm production are highly correlated. Without the male hormone, the male reproductive cells are not generated.
• In her book, Swan expands the scope of the challenge we face. It's not just about declining male testosterone or sperm. More broadly, it's about the growing incidence of a whole array of reproductive problems which affect both men and women and probably originate with the formation of sex organs in utero.
• For starters, rates of genital dysformation and "intersex variation" among newborns have been steadily rising. Among male newborns, these include testicular dysgenesis syndrome (SDS, including undescended testicles) and shorter anogenital distance (AGD). Both boys and girls are reaching puberty at an earlier age, which is associated (in boys) with lower subsequent testosterone levels and (in girls) with lower subsequent fertility.
• Among adult men, testicular germ cell cancer (known to be initiated in utero) is growing rapidly in throughout the developed world. Rates of erectile dysfunction is also rising by birth cohort, and this rise is steadily pulling down the average age of men presenting with ED. (One quarter are now under age 40.) Among adult women, rates of polycystic ovary syndrome and endometriosis are on the rise. And the observed rate of miscarriage is trending up (again) at about one percent per year.
• Swan doesn't stop there. It's not just our ability to have children that is reduced by these cohort-related developmental changes, she says. Our desire to have children is also affected--mainly by reducing sex drive and sexual activity in younger generations. (She cites the growth of "gender dysphoria" as corroborative evidence.)
• Well, OK: I've often reported on these trends myself, though I seldom link them to physiological changes. See "Millennials Don't Get Busy," "Millennial Teens Just Aren't Having Sex," "Japan: Land of the Young and the Sexless," "A 'Crisis of Love' on Valentine's Day," and "Celibacy Hits Record Highs."
• Swan concedes that her causal evidence on attitudinal change is not as strong as it is for physiological change. But she importantly adds that the sum total of these physiological trends results not only in lower fertility, but in worse health and shorter lifespans. That's because hormonal dysregulation affects how our bodies function. Lower testosterone levels in men, for example, are associated with higher all-cause mortality. Earlier puberty in women is associated with higher rates of breast cancer.
• So what's causing these trends? Swan agrees that modern lifestyles (poorer diet, less exercise, more obesity, more stress) are part of the explanation. And she has specific recommendations for how to improve these. She also agrees that the fertility challenge is made a lot harder by the fact that men and women are attempting to have children at ever-older ages. Age presents its own issues. Increasingly, the two challenges are compounding each other.
• But she insists that lifestyle and age aren't the whole story, especially in explaining the new sex organ dysformations we are observing in utero. I tend to agree with her. Keep in mind, for example, that the studies showing dramatic sperm count and testosterone declines are normalized for age, obesity, and observable chronic conditions.
• Moreover, the observed lifecycle connection between (say) obesity and low testosterone may not be what we think it is. The usual assumption is that obesity causes low testosterone. But it is equally true that low testosterone causes obesity. In other words, the direction of causation may go both ways.
• Let's cut to the chase. What is the rest of her story? In her opinion, what is the culprit? Swan points her finger at EDCs, endocrine disrupting chemicals, which are now routinely added to the gadgets we buy, the food we eat, and the homes we live in. Some of these, like certain phthalates and bisphenol A (BPS), have already been banned from most consumer products due to their known effects on fetal health. But dozens, perhaps hundreds, of similar chemicals--suspected but as yet untested--remain in use in plastics, pesticides, flame retardants, and a variety of other products.
• While many of these are known to cause deformities in lab animals at very low doses, thus far federal regulators such as the EPA, the CPSC, and the FDA don't have the bandwidth to track them or test for them, much less to try to regulate them. 
• But let me return to that question of dosage. IMO, this is the most persuasive (and scariest) part of Swan's argument. With many toxins, you need a really significant quantity to cause harm. With cigarettes, for example, it's amazing how much CO2, cyanide, and formaldehyde you can ingest into your lungs without doing lasting damage. The body is pretty good at self-repair, for a while at least.
• But with EDCs, just a few parts per million at just the right moment in gestational development (typically during the first trimester) can permanently alter embryonic development. That's because it doesn't have to damage the embryo. It just has to mimic or substitute for an endocrine which typically signals, at extraordinarily minute quantities, whether the embryo should grow one way or another.
• Because the male embryo is most dependent on endocrine signaling--through surges in testosterone, FSH (follicle-stimulating hormone) and LH (luteinizing hormone)--males are the ones most at risk from EDCs. And because many of the EDCs that trigger development in humans do the same in many mammals and birds, biologists are noticing similar changes in sex organs and reproductive habits in everything from otters and minks to alligators and birds. ("Lifestyle" changes probably aren't a factor for alligators.)
• My overall reaction to Swan's thesis: I find it intriguing, disquieting, and worth a lot more investigation. Few scientists would dispute her claims about the mutagenic effect of specific EDCs. Many more would be skeptical about her more sweeping claims--such as EDCs' role in triggering adolescent gender dysphoria or in pulling down global fertility rates. We know about plenty of social and cultural drivers which are backed by pretty solid evidence as well.
• Let's see what further research has to say. If it mostly backs Swan's argument, you can safely bet on two major trends. First, count on a robust boom in firms that specialize in assisted reproductive technologies like IVF, IUI, and ICSI (this is already an exploding VC sector). And second, expect heavy new regulatory screening of the "materials" giants in the S&P like Dow and Dupont and of the "industrial" giants they supply. In addition, of course, you'd better prepare to adjust your long-term projections of consumption, employment, and real GDP growth.
• We'll monitor the evidence as it arrives. I'm keeping an open mind.