•Patients taking experimental obesity drug lost more than 22.6kg, maker claims
•Cure for premature ejaculation that can help men last seven times longer in bed
•Involves zapping penis with electricity for 30 minutes at a time
Scientists have demonstrated how men with obesity can double their sperm count if they lose weight and maintain the weight loss.
In a new clinical study, researchers from the University of Copenhagen and Hvidovre Hospital show that men with obesity improve their semen quality if they lose weight — and maintain the weight loss.
Prof. Signe Torekov who headed the study together with Prof. Romain Barres at the Novo Nordisk Foundation Center for Basic Metabolic Research said: “It was surprising to us that such a big improvement can be shown in the semen quality in connection with a weight loss. And as 18 percent of Danes have obesity, this new knowledge may actually make a difference.”
The new findings may be good news for the fertility, as a link between higher sperm count and faster achievement of pregnancy has previously been shown.
The study has been published in the recognised journal Human Reproduction, which enjoys one of the highest rankings in the field of fertility. A total of 56 men with obesity participated, aged 18-65 years and with a body mass index between 32 and 43.
Signe Torekov explains that it has long been known that obesity is associated with reduced semen quality. Previous studies have also suggested a link between weight loss and increased semen quality, but these studies have had so few participants or such modest weight loss that it has been difficult to draw conclusions from them, she explains.
“But now we are ready to do just that. This is the first long-term randomised study, where we have shown that semen quality in men with obesity improve with a sustained weight loss,” says Signe Torekov at the Department of Biomedical Sciences.
“The men lost an average of 16.5 kg which increased the sperm concentration by 50 percent and the sperm count by 40 percent eight weeks since the weight loss. During the 52 weeks, the trial lasted following the weight loss, the men maintained the improved semen quality. But only the men who maintained the weight loss: after a year, these men had twice as many sperm cells as before their weight loss. The men who regained weight, lost the improvements in semen quality,” she explains.
Meanwhile, single-cell analysis of autopsied human testes suggests that abnormalities associated with aging sperm cells might be exacerbated by elevated body mass index (BMI). The research was published May 2 in the journal Developmental Cell.
Even though it is well established that older men display reduced reproductive health, testis aging remains poorly understood at the molecular and genomic level. Moreover, it has not been clear whether lifestyle or environmental factors affect this decline.
“Ageing may confer a combination of modest molecular changes that sensitize the testis for additional dysregulation, with pronounced dysregulation caused when aging is combined with additional factors such as obesity,” says co-senior author Bradley Cairns of the University of Utah School of Medicine.
To address this gap, Cairns and co-senior study author Jingtao Guo, also of the University of Utah School of Medicine, used single-cell RNA sequencing to profile more than 44,000 cells obtained from autopsy testis samples from four young men and eight older men. The older donors were screened for having offspring as young adults to ensure early-adult fertility.
The young samples clustered together and did not display molecular signatures of aging or a disrupted ability to produce sperm cells. Surprisingly, the older samples showed only modest age-related changes in stem cells that give rise to mature sperm, but were clearly classified into two distinct groups. The first group displayed an intact ability to produce sperm cells, with only weak molecular signatures that distinguished them from young samples. By contrast, the second group showed a very limited ability to develop sperm cells.
Notably, BMI emerged as a critical factor among older individuals. All donors from the first group had levels lower than 27, whereas all donors from the second group had levels higher than 30. Taken together, the results reveal possible molecular mechanisms underlying the complex testicular changes associated with aging, and their possible exacerbation by concurrent chronic conditions such as obesity.
Moving forward, larger patient cohorts are needed to fully validate the results. Another avenue for future research is to explore whether the testicular cells of older, heavy-set males show unique aging signatures, or whether they simply display accelerated aging. It is also not clear whether diet, exercise, diabetes, or altered hormone production play a role in testis aging. In addition, determining at what age the dysregulation of supporting testis cells emerges, and whether and how it may be reversible, may lead to improved medical guidance for older men.
“Our study reveals potential biomarkers for diagnosis of testis aging and directions for potential treatment of aging-related subfertility,” says Guo. “It also serves as a foundational dataset for the scientific community to study how human testis and fertility respond to ageing.”
Meanwhile, an experimental drug has enabled people with obesity or who are overweight to lose about 22.5 percent of their body weight, about 52 pounds (22.9 kilogrammes) on average, in a large trial, the drug’s maker announced on Thursday.
The company, Eli Lilly, has not yet submitted the data for publication in a peer-reviewed medical journal or presented them in a public setting. But the claims nonetheless amazed medical experts.
“Wow (and a double Wow!)” Dr. Sekar Kathiresan, chief executive of Verve Therapeutics, a company focusing on heart disease drugs, wrote in a tweet. Drugs like Eli Lilly’s, he added, are “truly going to revolutionize the treatment of obesity!!!”
Dr. Lee Kaplan, an obesity expert at the Massachusetts General Hospital, said that the drug’s effect “appears to be significantly better than any other anti-obesity medication that is currently available in the U.S.” The results, he added, are “very impressive.”
Kaplan who consults for a dozen pharmaceutical companies, including Eli Lilly, said he was not involved in the new trial or in the development of this drug.
On average, participants in the study weighed 231 pounds (104.78 kilogrammes) at the outset and had a body mass index, or B.M.I. — a commonly used measure of obesity — of 38. (Obesity is defined as a B.M.I. of 30 and higher.)
At the end of the study, those taking the higher doses of the Eli Lilly drug, called tirzepatide, weighed about 180 pounds (81.647 kilogrammes) and had a B.M.I. just below 30, on average. The results far exceed those usually seen in trials of weight-loss medications and are usually seen only in surgical patients.
Some trial participants lost enough weight to fall into the normal range, said Dr. Louis J. Aronne, director of the comprehensive weight control center at Weill Cornell Medicine, who worked with Eli Lilly as the study’s principal investigator.
Most of the people in the trial did not qualify for bariatric surgery, which is reserved for people with a B.M.I. over 40, or those with a B.M.I. from 35 to 40 with sleep apnea or Type 2 diabetes. The risk of developing diabetes is many times higher for people with obesity than for people without it.
An Eli Lilly spokeswoman said the company did not have a public timeline for seeking approval of the drug with the United States Food and Drug Administration.
Because obesity is a chronic medical condition, patients would need to take tirzepatide for a lifetime, as they do for blood pressure or cholesterol drugs, for example.
Dr. Robert F. Kushner, an obesity expert at Northwestern University’s Feinberg School of Medicine and a paid consultant to Novo Nordisk, said the new drug along with a similar but less effective one by Novo Nordisk, can close a so-called treatment gap.
Diet and exercise, combined with earlier obesity drugs, usually yield perhaps a 10 percent weight loss in patients. That is enough to improve health, but not nearly enough to make a big difference in the lives of peoples who are obese.
The only other treatment is bariatric surgery, which can result in substantial weight loss. But many people are ineligible or simply do not want the surgery.
With the Eli Lilly drug and Novo Nordisk’s semaglutide, which was recently approved, “we really are on the cusp of a new way of treatment,” Dr. Kushner said.
But prices may be a barrier. Insurers often will not pay for weight loss drugs. The Novo Nordisk drug, whose brand name is Wegovy, has a list price of $1,349.02 per month.
Experts worry that tirzepatide, if approved, might carry a price in the same range. Many people who could most benefit from weight loss may be unable to afford such expensive drugs.
The Eli Lilly study lasted 72 weeks and involved 2,539 participants. Many qualified as obese, while others were overweight but also had such risk factors as high blood pressure, high cholesterol levels, cardiovascular disease or obstructive sleep apnea.
They were divided into four groups. All received diet counseling to reduce their calorie intake by about 500 a day.
One group was randomly assigned to take a placebo, while the other three received doses of tirzepatide ranging from 5 milligrams to 15 milligrams. Patients injected themselves with the drug once a week.
Those taking the highest dose lost the most weight, the investigators found. Participants taking a placebo lost 2.4 percent of their weight, an average of 5 pounds, typical for a diet study.
Dr. Nadia Ahmad, senior medical director of Eli Lilly’s obesity program, said that seeing the results was an emotional moment for her.
“I don’t think I ever imagined we could reach this degree of weight loss with a medicine,” she said. “We only got this far with surgery.”
For decades, people who are overweight or have obesity were told that solving the problem was up to them. Diet and exercise were the prescriptions, and they simply did not work for many people. Most tried diet after diet, only to regain any weight they lost.
Last year, the situation began to change when Novo Nordisk received approval from the Food and Drug Administration to market semaglutide. The drug can elicit a 15 percent to 17 percent weight loss in people with obesity.
The medications are among a new class of drugs called incretins, which are naturally occurring hormones that slow stomach emptying, regulate insulin and decrease appetite. The side effects include nausea, vomiting and diarrhea. But most patients tolerate or are not bothered by these effects.
Incretins raise the bar for the sort of weight loss possible with drugs. But they also pose difficult questions about whether bariatric surgery is becoming a relic of the past. Already there are new versions of incretins in development that might be even more powerful than the Eli Lilly drug.
Even without them, Aronne said, the reductions observed with the Eli Lilly drug are “squarely in the range of surgical weight loss.”
Some patients who have had bariatric surgery describe mixed results. Sarah Bramblette, a board member of the Obesity Action Coalition, had bariatric surgery only to regain the weight. Now 44, she weighed 500 pounds when she had the operation 20 years ago, which enabled her to get down to 250 pounds. Over the years, though, her weight crept back up to 490 pounds. She needed heart surgery but was too heavy for the operating table. Diets — and she has tried them repeatedly — did not help.
Novo Nordisk’s semaglutide enabled her to get down to 430 pounds. Now, Ms. Bramblette said, she would like to try the Eli Lilly drug if it becomes available. “Trust me, I would not choose to be this size,” Ms. Bramblette said. “I need to lose weight.”
Meanwhile, scientists believe they have found a cure for premature ejaculation that can help men last seven times longer in bed. But it involves zapping the penis with electricity for half-an-hour at a time.
Doctors claim zapping the penis could combat premature ejaculation. One man who underwent the therapy was able to last roughly seven times longer in bed.
He underwent the treatment, which involved getting electrodes stuck onto his penis for 30 minutes at a time, three times a week.
Doctors in Lebanon, who treated the unidentified man, say he ejaculated within 40 seconds before seeking help.
But six months after completing the treatment, he was able to pleasure his girlfriend for almost five minutes before climaxing.
The Beirut-based medics called for studies to determine if the device can be rolled out as a safe and drug-free treatment for more patients.
Urologists at Lebanese University told the case of the 28-year-old patient, for whom drugs failed to help.
The patient had been in a relationship with his girlfriend for a year, medics wrote in the Asian Journal of Urology.
They had sex at least twice per week, and he would climax after just 40 seconds ‘on almost all occasions’.
Dr. Mohamad Moussa and colleagues trialled running an electrical current through his penis.
They hoped it would stimulate his dorsal penile nerve, one of the nerves that gathers movement and sensation information from the penis.
How does the device work? Medics place two round surface electrodes, attached to a nerve stimulator machine, on the penis shaft. One is placed at the base and the other is 2cm further up.
The device stimulates the dorsal penile nerve and interferes with the responses needed for muscles to contract as part of ejaculation. It had a frequency of 20 Hz, a pulse width of 200 μs and the wave was set between 20 mA and 60 mA.
The patient is given three 30-minute sessions per week, over the course of six months. Whenever the man underwent the zapping therapy, he had two electrodes placed on the surface of his penis.
One was placed at the bottom of his member, while the other sat around 2cm higher up. Over the course of six months, he underwent three 30-minute sessions each week — where he was exposed to a continuous current.
It had a frequency of 20 Hz, a pulse width of 200 μs and the wave was set between 20 mA and 60 mA. For comparison, patients who receive deep brain stimulation for Parkinson’s are exposed to more than 100 Hz.
Medics did not say whether the treatment was painful, but studies on similar devices said they can be used ‘without discomfort’.
The man used a stopwatch during sex to measure his intravaginal ejaculation latency time (IELT) — the time from vaginal penetration to ejaculation.
Before the treatment, his IELT was 40 seconds. But by the end of the six-month trial, his average IELT jumped to roughly three minutes and 54 seconds.
And the duration continued to rise even after he stopped using the device, reaching an average of five minutes 14 months later. That is the average length it takes for men to ejaculate, according to the British National Health Service (NHS).
The team said it is ‘not fully understood’ how the device works to improve premature ejaculation.
But during ejaculation, sperm is released through contraction of muscles between the anus and scrotum — called the bulbospongiosus and ischiocavernosus.
The medics believe stimulating the dorsal nerve interferes with the muscles and stops the contracting as quickly.
They said the procedure is non-invasive and called for further studies to determine whether it can be used as a safe and drug-free treatment for premature ejaculation.
Up to 40 per cent of men experience the problem at some point. But there is no definition for what is classed as a premature ejaculation.
The NHS advises men to seek help for premature ejaculation if half of their attempts at sex result are cut short. The NHS also advises men to try masturbating before sex, using a thick condom and taking breaks during sex before seeking medical help.
Premature ejaculation can be caused by prostate problems and taking recreational drugs, as well as by stress and anxiety.
Current treatments include dapoxetine tablets, which is taken a few hours before sex, and lidocaine and prilocaine gels, which delay ejaculation.
