Preventing homosexuality in utero: Could we? Would we? Should we?

A workhorse drug that's been around for decades has, in recent weeks, stirred up a biomedical debate that will likely resonate with any parent who's ever asked him or herself: If I could prevent my child from being gay, would I?

Dexamethasone is a corticosteroid that has been widely used in the treatment of arthritis, of intestinal, kidney and thyroid disease, in certain kinds of cancers. It's also been prescribed to — and used by — pregnant women carrying female babies who are at genetic risk of a condition called congenital adrenal hyperplasia, or CAH.

Children born with the genetic anomaly will need a lifetime of medication to ensure their normal growth, sexual development and reproductive function. But for girls, one manifestation of CAH is evident at birth: her external genitalia will look more masculine than feminine. The resulting person used to be called a hermaphrodite. The preferred term now is intersex, a condition of gender ambiguity that can be caused by a number of different conditions.

Dexamethasone, when administered in utero, appears to correct the development of a female fetus' genitalia. As a result, it relieves parents and child of a difficult decision — to have later corrective surgery, with all of its risks.

That a parent should take it upon him or herself to "correct" a child's ambiguous gender identity is debatable enough. (The Intersex Society of North America maintains that "parents' distress must not be treated by surgery on the child.") What ignites serious controversy is a side effect of  prenatal dexamethasone — its ability to feminize, not just the external genitalia of a girl with CAH, but her internal outlook and her behavior. That is significant because among CAH's more subtle effects, according to Mount Sinai Medical Center endocrinologist Dr. Maria I. New, is that women who have it tend to be more masculine in their behavior and interests, including sexual attraction to women. New has been a leading researcher on CAH and, in an earlier practice, is reported to have prescribed dexamethasone. She and a research collaborator, Columbia University psychologist Heino F.L. Meyer-Bahlburg, has investigated at length the "psychosocial" as well as medical issues faced by those with CAH.

In short, dexamethasone seems to hold the promise not only of sparing a child a difficult and risky surgery, it may also redirect a sexual trajectory that will lead to bisexuality or lesbianism.

That, say bioethicists, is going too far. In a recent posting on the Bioethics Forum of the Hastings Center, a nonpartisan bioethics institute based in Garrison, N.Y., Alice Dreger, Ellen K. Feder and Anne Tamar-Mattis warn that treatment of the external manifestations of CAH are debaeable enough in and of themselves: But, in this case, that treatment will make it possible for some parents to take actions motivated -- at least in part -- by a desire to prevent their child from becoming a homosexual.

Dreger, Feder and Tamar-Mattis suggest that in insisting that homosexuality is not a choice but a biologically determined fact of identity, gay and lesbian rights activists may have set themselves up for medical researchers to see sexual orientation as a condition that can be "fixed." They "should be wary of claims that the innateness of homosexuality will lead to liberation," they wrote. Instead, it might "very well lead to new means of pathologization and prevention," write the bioethicists.

Also unclear is whether the use of dexamethasone by pregnant women is safe — or for that matter, effective. Neither has been demonstrated by clinical trials. The prescribing of a drug in treatment of a condition other than that for which the Food and Drug Administration has approved it — called off-label — is very common and legal. But the debatable use of dexamethasone in pregnant women has caused sufficient concern among endocrinologists that the Endocrine Society next month is expected to issue a consensus document warning physicians who prescribe prenatal dexamethasone for CAH that the treatment should be considered experimental. That imposes far greater ethical strictures on physicians: They must seek the approval of an ethics and safety review board and satisfy other conditions designed to protect a patient's rights. 

Want to know more about what researchers have learned about the bases of homosexuality, and the ethical debates that result? Here's an article on the subject from the LA Times Health section.

--Melissa Healy

Long-term steroid use damages the heart, research shows

Long-term use of anabolic steroids damages the heart more than researchers previously believed and could be setting up many users for heart disease and death, researchers reported Tuesday. The drugs, which include testosterone and related hormones, are taken by weight lifters and other athletes to boost muscle mass. Research reported in the journal Circulation: Heart Failure shows that they can severely impair the heart's ability to pump blood throughout the body.

Previously known side effects of the drugs include liver tumors, jaundice, high blood pressure, shrinkage of the testicles, reduced sperm count, development of breasts, paranoid jealousy, extreme irritability and impaired judgment.

Because some studies have also suggested an effect on the heart, Dr. Aaron L. Baggish of Massachusetts General Hospital in Boston and his colleagues decided to study the effects more carefully. They recruited 12 male weight lifters, average age 40, who reported taking about 675 milligrams of steroids per week for nine years. They were compared with seven closely matched weight lifters who had not taken the drugs.

The researchers used echocardiography to measure the so-called ejection fraction, the proportion of blood in the left ventricle forced out of the heart with each contraction. In healthy people, the ejection fraction is normally somewhere between 55% and 70%. In the steroid-taking group, the average ejection fraction was about 50%, compared to 59% in the group that did not take drugs. Such low ejection fractions are associated with an increased risk of heart disease and heart failure. The steroid users also had significantly impaired diastolic function, impeding the ventricle's ability to relax and fill with blood.

Previous studies have not found such clear-cut problems, Baggish said. That may be in part because they were conducted in Europe and athletes may have been taking different drugs. Also, most previous studies have looked at professional athletes, who might be expected to be healthier, while this one focused on recreational athletes.

"What we hope is that people start recognizing steroid use as a potential cause of heart disease and a cause of otherwise unexplained heart dysfunction in young people," Baggish said in a statement.

-- Thomas H. Maugh II

Photo: Weight lifters who take anabolic steroids to increase their muscle mass run the risk of damaging their heart's ability to pump blood. Credit: EPA / Anatoly Maltsev

What, exactly, is Actovegin?

The drug made a media debut today when it was reported that Canadian physician Anthony Galea, who has previously treated Tiger Woods, is under investigation by the FBI for giving athletes performance-enhancing drugs.

According to news reports, Galea was arrested Oct. 15 by Canadian authorities – officials said they had earlier found human growth hormone, Actovegin and two other drugs in a medical bag in his assistant’s car. Actovegin, which is essentially calf’s blood extract, has been used in the treatment of circulatory disorders but has not been approved for sale in the U.S. by the Food and Drug Administration.

Actovegin isn’t really one of your known quantities – there’s no mention of it at the FDA website. By contrast, “human growth hormone” turns up more than 2,000 hits. It’s sold by Nycomed, a Swiss-based company. From the product description:

Actovegin® produces an organ-unrelated increase of the cellular energy metabolism. The activity is confirmed by measurement of the increased uptake and of the elevated utilization of glucose and oxygen. These two effects are coupled and they result in a rise of the ATP-turnover and thus in a greater provision of energy in the cell.

“We don’t have it on our books,” said Karen Riley, a media officer with the FDA. “It would have to go through an FDA approval process, and I don’t have any record of that product.”

One might begin to suspect that calf blood extract is another way of saying "snake oil," but wait ...ClinicalTrials.gov turns up one hit – a recent trial related to polyneuropathy, or nerve malfunctions in the extremities. It was performed under Russian authority, in Kazakhstan.

Why is it on a U.S. site devoted to clinical trials? “I don't know, I was surprised to see it,” Riley said.

Want to find out if all your prescriptions pass muster? The FDA provides some guidelines here.

-- Amina Khan

Doctors paint portrait of steroid side effects, as FDA finds new targets

The body-building world is not for the weak of body. And body-building supplements might not be for the faint of heart. Three new case reports highlight what can happen.

In a report published in the August issue of Journal of Clinical Gastroenterology, doctors at Henry Ford Hospital in Detroit recount the medical ordeal of otherwise healthy men (described as "unwitting victims") who consumed dietary supplements laced (perhaps more than laced) with steroids. Topping the list are nausea, anorexia, jaundice, extreme itching and kidney failure. Then, when the light bulb goes off, the cessation of such supplements and hospitalization.

The news release contains these details:

"A 21-year-old previously healthy white male presented with nausea, anorexia, jaundice, and severe itching. He denied alcohol consumption or illicit drug use and took no prescription medications on a regular basis but did acknowledge use of the over-the-counter supplement Superdrol, a bodybuilding agent containing methasteron, for several months before his presentation."

"A previously healthy 30-year-old white businessman initially presented to a hospital with a 5-week history of jaundice and severe itching. His medications included omeprazole and herbal supplements including chondroitin sulfate, glucosamine, glutamine, and creatine. He also acknowledged the use of a bodybuilding supplement that contained dehydroepiandrosterone. Concerned about his symptoms, he stopped consuming this supplement just before his hospitalization."

"A 38-year-old previously healthy white man initially presented for evaluation of jaundice. He first noticed the onset of scleral icterus 6 weeks previously. His symptoms included intense and worsening itching, generalized fatigue, nausea, decreased energy, and weight loss. His past history was unremarkable. He denied alcohol or illicit drug use and used no prescription medications. Owing to worsening of his symptoms and renal failure, he was admitted to the hospital."

And here's the abstract from the journal. It states:

"The illegal enrichment of anabolic androgenic steroids in over-the-counter dietary supplements is well documented, but the health consequences have not been widely recognized."

Such case reports should help. In the meantime, the Food and Drug Administration is targeting the makers of steroid-containing supplements. The new doctor-as-witness accounts follow a recall last week from the agency telling consumers to stop using bodybuilding products containing steroids or steroid-like substances.

Here's the advisory and an L.A. Times post.

That advisory focused on the risk of liver injury, stroke, kidney failure and pulmonary embolism. It specifically targeted supplements sold by American Cellular Laboratories, including TREN-Xtreme, MASS Xtreme, ESTRO Xtreme, AH-89-Xtreme, HMG Xtreme, MMA-3 Xtreme, VNS-9 Xtreme and TT-40-Xtreme.

The advisory went beyond those products, however, stating: "Due to the potentially serious health risks associated with using these types of products, the FDA recommends that consumers immediately stop using all body building products that claim to contain steroids or steroid-like substances."

And then there was the recall that same day of a dietary supplement sold as S-DROL.

That supplement was found to contain the steroid desoxymethyltestosterone. 

An entry on the bodybuilding website www.marombapura.com says of the substance, also known as Madol: "The drug is too potent, too synthetic, too controversial, too much an obvious anabolic steroid for the FDA to drop the ball. If you want this steroid and can still find it, you better stock up quick!

Guess so.

-- Tami Dennis

Photo: Weight-lifting pays off in a positive way, at least to some degree; supplements that lead to kidney failure and liver failure might not.

Credit: Associated Press

Manny Ramirez probably wasn't pregnant

Human chorionic gonadotropin, which is allegedly what got Manny Ramirez suspended for 50 games, is a hormone produced by the embryo during pregnancy. But it can do so much more . . .

In clinical settings, it's used to treat infertility in women by stimulating the ovaries to release eggs. In prepubescent boys, it's used to encourage normal sexual development and the natural lowering of the testicles into the scrotum.

In men, it's used to bump up testosterone levels -- it tells the testes to release testosterone.  

Here's a good overview, from WebMD, of the hormone's more traditional medical uses.

As Dr. Gary I. Wadler, a sports medicine expert and a key official of the World Anti-Doping Agency, says in today's L.A. Times story Baseball's anti-doping program faces renewed scrutiny in light of Ramirez case: "In the legitimate world, HCG is used for infertility [by women] or for delayed puberty. . . . But for a man of his age [36] with a testosterone deficiency, there are much better drugs." 

If you're wondering about the ways to treat that condition, known as male hypogonadism, think patches, gels and, of course, the efficient injection. Oral medicines, convenient though they are, have some particularly unpleasant side effects.

Here are two good descriptions of treatment, one from the Mayo Clinic and one from the Urology Channel. The latter, as a bonus, includes a quiz via which you can check yourself for symptoms of low testosterone. (Do you have low sex drive? Loss of energy? A decrease in strength or endurance?)

But perhaps we digress. (To be fair -- perhaps not.)  HCG also has other uses, hence the brouhaha.

As anabolicsteroidsguide.com notes: "In a man the luteinizing hormone stimulates the Leydigs cells in the testes; this in turn stimulates production of androgenic hormones (testosterone). For this reason athletes use injectable hCG to increase the testosterone production. hCG is often used in combination with anabolic/androgenic steroids during or after treatment."

And from steroid.com: "HCG is no doubt one of the most misused, misunderstood and underutilized tools in bodybuilding pharmacology we have available."

-- Tami Dennis  

Photo: Dodger Manny Ramirez warms up before a game in April.

Credit: Christian Petersen/AFP/Getty Images

Ethnicity matters in detecting steroid use

Swiss researchers are calling for an end to the current steroid doping tests used in international sports because the tests do not account for genetic differences among various ethnic groups and may be inaccurate.

The study, published online today in the British Journal of Sports Medicine, comes at a time when steroid use has clouded the presumed accomplishments of numerous international sports stars, such as baseball slugger Barry Bonds, who awaits trial for tax evasion and perjury relating to his alleged steroid use.

Evidence of steroid abuse is determined by the ratio of testosterone to epitestosterone in the urine. The threshold for evidence of possible testosterone doping is set at four or above for all athletes. (Another test is required to confirm doping.) Previous research, however, has shown that variations in a particular gene, UGT2B17, affects metabolism and the rate at which testosterone is passed out of the body in urine. Differences in this measurement between men of white and Asian ethnic backgrounds have been documented.

In the new study, Swiss researchers demonstrated the inaccuracy of using a threshold of four for everyone. They added steroids to urine samples from 171 athletes: 57 men of black African ethnicity, 32 of Asian ethnicity, 32 of Hispanic ethnicity and 50 Caucasians. The men were soccer players between the ages of 18 and 36. The researchers found a variation in the UGT2B17 gene in 22% of the athletes, including eight out of 10 Asian men.

Based on the genetic variations, the researchers recalibrated the thresholds for suspected doping for each group and concluded an appropriate threshold would be 5.6 for men of black African ethnicity, 5.7 for Caucasians, 5.8 for Hispanics and 3.8 for Asian men.

A more accurate approach to steroid doping would take into account each individual's genetic profile, said the study authors, from the Swiss Laboratory for Doping Analysis.

-- Shari Roan

Photo: Greg Anderson, Barry Bonds' personal trainer, is shown at a hearing on Feb. 27. Anderson may be ordered to prison if he does not cooperate with a grand jury by giving testimony about Bonds' alleged steroid use. Credit: Justin Sullivan / Getty Images

Steroids in shades of gray*

You’d expect a documentary about anabolic steroids circa 2008 to be heavy on the dark side of the substance — the horrific side effects when abused, how it’s infiltrating youth athletics, the way it’s ruined elite and professional sports competition, etc.

Don't be so quick to judge "Bigger, Stronger, Faster," a new movie debuting Friday in New York and Los Angeles (the film opens wide in June and July). Director Christopher Bell has colored the movie in a palette of grays, even presenting a credible argument that maybe steroids aren’t the devil-spawn drugs some believe them to be.

"I had two brothers on steroids during the making of the film," says Bell, a USC film school grad from Poughkeepsie, N.Y., who did a stint working at Gold’s Gym in Venice and directed the short film "Billy Jones." Bell, who does a Michael Moore/Morgan Spurlock turn and appears in the film, originally considered documenting gym culture, but his brothers were willing to talk about their own steroid use to present another side of the story. "Also," says Bell, "at the time Congress was saying it was a black and white issue, and going through my life as a power lifter and being around steroids, I knew there was a gray area, and I wanted to present it in a different way."

He has, interviewing athletes, fitness models, doctors and sports fans about their attitude toward steroids. The film presents a mixed bag of facts, emotions and misinformation that will likely have even hard-liners reconsidering their views. For example, Bell points out that different forms of steroids are legally and routinely used in healthcare, and that " 'roid rage" isn’t a well-documented medical phenomenon. And although steroids, supplements and human growth hormone have horribly tainted elite and professional sports (as financial stakes stretch higher and higher), Bell makes the case that Americans like their sports heroes big and strong, and expects them to be winners. So aren’t we complicit in this as well?"

"As an athlete," says Bell, "you invest so much time and energy into pursuing your dream, and then all of a sudden you come to a crossroads — do you throw away all that time and effort, or be the person who wins at all costs? I found people on both sides of the coin. ... We always say that cheaters never prosper, but the people who are doing (steroids) are the people who are winning. It’s hard to tell people not to do it when they’re victorious. But if we want them to stop, are we doing anything to stop it?

At the heart of the film is the toll steroid use takes on Bell’s own family. In the film, Bell’s older brother Mike (nicknamed "Mad Dog") wants a shot at World Wrestling Entertainment fame, while the younger, Mark (nicknamed "Smelly") coaches high school and competes in power lifting. Their use of the substance is a source of consternation among family members, but we see the parents cheering wildly at competitions. It’s a scenario that’s undoubtedly being played out in various forms in many families.

Bell, by the way, hasn’t budged on his stance on ’roids: "I always thought it was cheating and against the rules and that people shouldn’t do it," he says. "If people learned more about nutrition and training, they’d be way better off."

*Update: Read more Times coverage of the movie here and Carina Chocano's movie review here.

--Jeannine Stein

Photo of Mike, Chris and Mark Bell courtesy of Magnolia Films