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

Testosterone gel linked to increase in heart problems in frail men, study finds

Many men use a testosterone supplement to treat symptoms linked to testosterone deficiency in older age, such as poor libido and deteriorating muscle strength. However, such treatment appears to come with additional health risks for frail, elderly men who use the gel to increase their strength and mobility.

Researchers reported Wednesday that a study designed to assess the risks and benefits of testosterone replacement therapy in men ages 65 and older who had mobility problems was stopped early -- in December 2009 -- because of a much higher rate of cardiovascular problems in the men receiving testosterone compared with those receiving a placebo gel.

The study, led by researchers at Boston University and funded by the National Institute on Aging, included 209 men, half of whom used testosterone gel daily for six months. The average age of the men in the study was 74. All of the men in the study had limited mobility and a high prevalence of chronic disease. However, among the 106 men using testosterone gel, 23 had cardiovascular-related events compared with only five men in the 103-person placebo gel group. The study is published online in the New England Journal of Medicine.

It's difficult to know just what to make of this study, the authors acknowledged. There was a broad range of cardiovascular events, including heart attack, stroke, death from suspected heart attack, exacerbation of congestive heart failure, atrial fibrillation, swelling, chest pain and other milder symptoms. With such a diversity of events, it's hard to pinpoint how testosterone replacement therapy may be responsible. The doses of testosterone used in the trial may have been higher than in previous testosterone studies that have not found cardiovascular risks. Moreover, the trial was small and was stopped early.

The elderly men using testosterone did show increased strength in leg-press and chest-press strength and in stair climbing while carrying a load.

As for younger and healthier men who use testosterone gel, it's doubtful this study can be applied to them, the authors said. Previous studies of testosterone gel in other groups of men have not shown significant increases in cardiovascular risks. "Caution is also warranted in extrapolating these findings to other doses and formulations of testosterone or to other populations, particularly young men who have hypogonadism without cardiovascular disease or limitations in mobility," they wrote.

However, long-term studies on the risks and benefits of testosterone therapy in men of all ages are lacking, according to a recent story in the Los Angeles Times. Meanwhile, the availability of testosterone in gel form has led to a huge jump in prescriptions in the U.S.; 3.3 million prescriptions were filled in 2008 compared to 64,800 in 1999, according to one pharmaceutical data company.

As for older men in poorer health: "The authors note that physicians and patients, especially older men, should consider this study's findings on adverse effects along with other information on the risks and benefits of testosterone therapy," officials from the NIA said in a statement. Further research is needed to clarify the safety issues raised by the trial, the authors note.

Additional trials on the risks and benefits of testosterone therapy in men are ongoing, the NIA statement said. Those trials will continue although investigators and participants will be advised of the findings of the Boston University study.

-- Shari Roan

Photo credit: Stephen Sedam  /  Los Angeles Times

Young breast-cancer patients often give up on hormonal therapy

After undergoing treatment for breast cancer, many women -- especially young women -- fail to complete subsequent therapy intended to reduce their risk of recurrence, according to researchers.

In a study of 8,769 women prescribed hormonal therapy for breast cancer, researchers from Columbia University Medical Center in New York and Kaiser Permanente in Northern California found that just under half -- 49% -- completed the recommended course.

Hormonal therapy is routinely prescribed for about 60% of breast cancer patients, that is, those who have tumors fueled by the female sex hormones estrogen and progesterone, said Dr. Dawn Hershman, who led the study. The therapy reduces the risk of cancer recurrence, and patients are advised to take it for at least five years.

“There are a lot of outstanding treatments for breast cancer, but it’s clear that if people don’t get them for as long as they should, they won’t get the full benefits,” said Hershman, an associate professor of medicine and epidemiology at Columbia.

The study, published online Monday in the Journal of Clinical Oncology, used the pharmacy records -- specifically, prescriptions and refill dates for tamoxifen, aromatase inhibitors, or both
-- from multiple Kaiser Permantes in Northern California of women diagnosed with Stage I, II or III hormone-sensitive breast cancer between 1997 and 2007.  Other studies had found that breast cancer patients often fail to complete such therapy, but this study was one of the largest, helping to clarify which age groups are most at risk of discontinuing the treatment.

In short, women under the age of 40 were the most likely to give up on the treatment.

“This helps us to see which groups are most likely to be affected and stop treatment, so that we can then focus our efforts on them,” Hershman said.  

The hormone treatments’ side effects might be more likely to lower the quality of life for younger women than for older women, researchers speculated. The cost of medication or insurance co-payments and younger women’s more inherent sense of immortality could also lead them to discontinue treatment.

Further, Hershman added, some women may discontinue their medication because, as time goes on, their cancer has “become something of the past and they do not want to be reminded of it.”

The study also found that women over the age of 75 are more likely than women in the middle age group -- between between the ages of 40 and 75 -- to discontinue their treatment early. Researchers said that older women, who may already be burdened with taking pills to treat other ailments, might not feel that continuing hormonal therapy for  so long is worth the effort.

Here’s an explainer from WebMD on breast cancer and hormone therapy.

-- Jessie Schiewe

Photo: Many breast cancers are first found with a mammogram. But interpreting the images can be difficult. A dense breast is shown at the left; a fatty breast is on the right.

Credit: National Cancer Institute

FDA panel recommends approval of 5-day 'morning after' pill

A Food and Drug Administration advisory panel Thursday recommended that the agency approve a "morning after" pill that is effective for five days after unprotected sex, providing an alternative to existing drugs that can be used only for three days. The agency is not required to follow the advice of its advisory panels, but usually does.

The new drug, whose proposed brand name is ella, is already marketed in Europe as ellaOne. It blocks the effect of progesterone, a female hormone that spurs ovulation. There has been spirited debate about whether the drug simply blocks ovulation or, because it is related to the abortion drug RU-486, whether it actually produces an abortion. The Washington Post and the New York Times have outlined the parameters of the debate.

The agency has set no timetable for a decision. The drug will most likely be available only by prescription, at least initially.

-- Thomas H. Maugh II

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Hormone patch not as likely as the pill to cause stroke, study finds

Hormone replacement therapy is known to increase the risk of stroke. However, a new study indicates that a low-dose skin patch may be less risky than the HRT pill.

The risks of HRT have been debated for years, but the medications are still popular choices for the treatment of menopause-related symptoms, such as hot flashes. Data from the long-running Women's Health Initiative linked HRT pills to a slightly increased risk of stroke, especially in the second year of use or thereafter. However, that study did not examine the risks of hormones from a different delivery system, such as a patch.

In the new study, researchers looked at the records of 870,000 women ages 50 to 79 from 1987 to 2006. They identified 15,710 women who had strokes and compared them with 59,958 women who did not have strokes. They found there was no higher risk of stroke with a low-dose estrogen patch compared with not using HRT. However the risk of stroke increased up to 88% with high-dose patches compared with no use of hormones. The risk of stroke was increased about 25% from the HRT pill compared with no use of hormones.

The research suggests that more effort should be put into understanding how the route of administration of hormones may change the risk profile.

The study was released this week online by the British Medical Journal.

-- Shari Roan

Photo: A packet of hormone replacement therapy pills. Credit: Eric Boyd / Los Angeles Times

50 years of 'the pill' -- and here's yet another one

"The pill" appears to be evolving, but to what end? On Thursday, the Food and Drug Administration approved a new oral contraceptive called Natazia. It's the first to offer doses of progestin and estrogen that vary at four times throughout the 28-day treatment cycle.  

Here's the FDA announcement of the new oral contraceptive.

And here's a recent Health section story that provides an explainer on the evolution of birth control pills (they're not just for preventing pregnancy any more) -- and how two of the offerings in particular have proved especially controversial in recent years. That story, "Birth control pill concerns bring lawsuits but few solid answers," begins:

"When the oral contraceptives Yasmin and Yaz came on the market in 2001 and 2006, respectively, they were thought to be safer than other birth control pills because they contained a different kind of synthetic progestin.

But in a flurry of lawsuits against the pills' maker, Bayer HealthCare, attorneys claim that the progestin contained in the pills, drospirenone, is the cause of health problems, including deep vein thrombosis (blood clots in the deep veins), strokes, heart attacks and gallbladder disease."

Meanwhile, Times staff writer Shari Roan offered a perspective worth mulling this week amid all the reflections on the 50th anniversary of oral contraceptives. As she notes in that story, "'The pill': 50 years after":

"But despite the freedom in career and family planning it extended to so many women and couples, the pill has not fulfilled one big hope. Fifty years on, about half of all pregnancies in the U.S. are unintended and 22% of pregnancies end in abortion.

'It's not going to be the answer to unintended pregnancy — we can be sure of that,' said James Trussell, director of Princeton University's Office of Population Research and a leading authority on contraception.

Trussell thinks that the pill's time is passing — and that the future lies instead with fool-proof contraceptives that require almost no thought or action."

The new pill still requires both thought and action. 

Not all contraceptives do. Here's more on hormonal contraceptives from the American Congress of Obstetricians and Gynecologists, including those that require no daily reminders.

Plus, here's more complete Natazia information from manufacturer Bayer.

-- Tami Dennis

Photo: Which to choose? The (by now) traditional hormonal contraceptive in pill form or an injectable version. Credit: Associated Press

Book Review: 'The New Me Diet' by Jade Teta and Keoni Teta

“Eat more, work out less, and actually lose weight while you rest.” What chubby, chunky or downright hefty gal or guy trying to knock off the pounds wouldn’t want some of that?

The subtitle on the cover of “The New Me Diet” may be technically correct but could also be a little misleading. If you read it to mean “Order up a large pizza, grab the TV remote and lose weight while you channel surf” -- well, no.

What it really means is this: Eat a diet composed of an unlimited quantity of most vegetables, certain fruits and lean proteins; some fat; and a small amount of whole grains, legumes and beans. Do a 30-minute interval and weight training workout that incorporates periods of rest three times a week, and walk every day for 30 to 60 minutes. And you will lose weight.

Now that sounds doable.

"Me Diet" authors Jade Teta and Keoni Teta are brothers who each have a couple of decades of experience as personal trainers and degrees in biochemistry and naturopathic medicine, among other health and fitness credentials. But though their backgrounds are similar, their body types and metabolisms are different, they say.

Their curiosity about why food and exercise affect people differently led them to develop what they dub their Metabolic Effect, or ME, program, which they say is based on the new science of hormonal fat burning. Translated, that means that certain hormones control how fat is stored and burned in the body. The Tetas say you can manipulate those hormones by what you eat and how you exercise.

Their book spends a few pages discussing the science behind their program but quickly launches into the practical matter of how to make it work for you. They divide people into three different types -- sugar burners, muscle burners and mixed burners -- and offer a quiz for readers to determine which type they are.

Lung cancer and women: heartache and hope

Lung cancer has been the leading cause of cancer death among women since 1987, claiming the lives of 70,490 women in 2009. But it's still called the "hidden women's cancer," because other cancers that are common among women — breast cancer in particular — are so well known and well funded.

So, it's probably high time that someone put out a comprehensive overview of the disease's specific toll on women. And on Monday, that's just what the Brigham & Women's Hospital and the Lung Cancer Alliance did. The result is "Out of the Shadows: Women and Lung Cancer," an authoritative roundup of research on how many and which women get lung cancer, who survives, what treatments are in the works and how those treatments are likely to affect female lung cancer patients differently from men.

Among the most striking findings: Among women lung cancer patients, 1 in 5 never smoked cigarettes, and an increasing number of these women are younger patients. Among men, 1 in 12 diagnosed with lung cancer never smoked. Of the 20,000 to 25,000 people who never smoked to be diagnosed yearly with lung cancer, 60% are women.

Other striking facts:

— Women are more likely than men to be diagnosed with adenocarcinoma, a form of the disease that is both operable and that appears to be linked to estrogen.

— Women who smoke seem to have markedly more DNA damage and mutation than do men, even if they smoke less. 

— Women who develop lung cancer survive longer than do men, no matter how early it was discovered, what type of lung cancer it is or how it was treated.

The report contains an excellent discussion of the research and debate surrounding early screening for lung cancer, as well as a provocative look at how and why research funding for lung cancer, per patient death, is lower than almost any of the other major cancers. The main reason, of course, is well known to lung cancer patients and their families: the rather cruel assumption, given its strong link to smoking, that this is a cancer one brings upon oneself.

— Melissa Healy

Rodent of the Week: Women, estrogen and lung cancer

Lung cancer is the leading cause of cancer deaths among women, with most cases linked to smoking. But not everyone who gets lung cancer smokes. Indeed, among nonsmokers, lung cancer is still the seventh most-common cause of cancer worldwide. Most of the lung cancer cases among nonsmokers are in women.

Researchers now have some clues about this mysterious connection. In a study presented earlier this week at the annual meeting of the American Assn. for Cancer Research, scientists found that smoke triggers changes in gene expression in the lungs of female mice. That's not surprising. But those changes include increasing the activity of genes involved in estrogen metabolism. Based on these data, the study's authors suggest that estrogen metabolism (the process by which estrogen becomes available for use) may contribute to lung cancer in nonsmoking women as well.

The researchers, at Fox Chase Cancer Center in Philadelphia, found 10 genes were expressed in the lungs of female mice exposed to smoke. The gene most affected by smoke was one that is a key enzyme for estrogen metabolism.

It's possible that estrogen plays a role in lung cancer in women in a similar way as it does in breast cancer. Other studies have shown women with lung cancer who take hormone replacement therapy (which replaces estrogen) have worse outcomes than do women who don't take hormone therapy.

— Shari Roan

Photo credit: Advanced Cell Technology Inc.

Book Review: 'The Perfect 10 Diet' by Michael Aziz

You might say Dr. Michael Aziz believes in the middle way. In his new book, "The Perfect 10 Diet," Aziz proposes a weight-loss plan that combines elements of both low- and high-carb diets -- and rejects aspects of each of them as well. 

It's all about finding balance, the board-certified internist writes. Specifically, Aziz -- founder and director of New York's Midtown Integrative Medicine -- believes we need to be eating the right foods to balance 10 key hormones that contribute to our weight and health.

These hormones are insulin, glucagon, leptin, thyroid hormone, human growth hormone, cortisol and DHEA, as well as estrogen, progesterone and testosterone. The latter sex hormones may not be crucial to survival, he writes, but they can affect how you age, look and feel.

Aziz is not shy about proclaiming what his program will do for you. His diet isn't just for losing weight, he writes; it will benefit anyone who wishes to reduce the risk of many cancers, boost memory, lower anxiety, improve his or her sex life and have a glowing complexion -- to name just a few promised results.

What does Aziz propose? First of all -- and he will find little argument among many nutritionists here -- he says to cut out sugar, products containing high-fructose corn syrup and anything made with white flour. Low-fat and fat-free baked products are to be avoided as well. Steer clear of soy protein isolates, processed meats with nitrates and anything with monosodium glutamate, he says. 

And while you're cleaning out your cupboards, get rid of the refined polyunsaturated vegetable oils, as well as the margarine and anything containing trans fats. These are "killer" fats, in his view.

That doesn't mean all fats are bad. In fact, he believes the popularity of low-fat diets is one reason for the obesity epidemic. He says to choose full-fat organic milk, butter, eggs, cheese and yogurt products in moderation rather than the low-fat versions because saturated fats and cholesterol-rich foods are needed to satisfy appetite, maintain sex hormone levels and assist in proper cell functioning. Also on his "good" fat list are avocados and nuts and olive, palm and coconut oils.

His Perfect 10 food pyramid has at its base fiber-rich vegetables, fruits and fats from natural sources. Above that on the pyramid is protein from poultry, fish and other seafood. Whole grains, nuts, legumes and calcium supplements or dairy are included in smaller amounts. Refined carbs and red meat should be eaten only occasionally.

His ideal is a diet that gets 40% of its calories from carbohydrates, 40% from fat and 20% from protein. This proportion, and the foods he recommends, will support the hormones needed for health, vitality and weight loss, he says. 

To get started losing weight, he offers a three-stage plan. The first stage is a variation on the so-called Paleolithic diet and focuses on vegetables, fruits, poultry, seafood, beans, nuts and seeds. He says most people lose 10 to 14 pounds in this three-week phase. Subsequent stages -- the last being a maintenance phase --  add more foods in moderation.

There's much that makes sense in Aziz's program -- once you get past the sweeping claims ("The Perfect 10 Diet is the only diet in the world that will help you balance these ten important hormones"), unsupported statements ("Centenarians ... all have one thing in common -- low insulin levels") and occasional leaps of logic.

Though his book may not win awards for its prose, it's clear the doctor has much passion for his subject. His diet apparently has a following, and his message is one that some may want to hear.

-- Anne Colby

Photo: "The Perfect 10 Diet," Michael Aziz, Cumberland House, $24.99

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