1. Symptomatic Testosterone Deficiency Relatively Rare in Men
2. New Treatment Option for Life-Threatening Symptom of Parathyroid Cancer
3. Maternal Weight Linked to Child Body Composition
4. New Patient Guide on the Management of Maternal Hypothyroidism Before, During and After Pregnancy Now Available from The Hormone Foundation

1. Symptomatic Testosterone Deficiency Relatively Rare in Men

As men age, their testosterone levels decline gradually. However, a new study reveals that relatively few men, only 5.6 percent of the male population, actually suffer from low testosterone accompanied by clinical symptoms. That percentage, however, rises substantially with age.

Low testosterone levels are typically defined as less than 300 ng/dL (nanograms per deciliter) of total testosterone and less than 5 ng/dL of free testosterone. Free testosterone is the amount of the hormone unbound to other proteins and is “free” to work inside the body. “Low levels of testosterone impact many aspects of male physiology,” said Andre B. Araujo, Ph.D., a research scientist at the New England Research Institutes in Watertown, Mass., and lead author of the study. “This is particularly significant because the ongoing aging of the U.S. male population is likely to cause the number of men suffering from androgen deficiency to increase appreciably.”

Consistent with a recently issued Clinical Practice Guideline from the Endocrine Society, symptomatic androgen deficiency in the study by Araujo and colleagues is defined as low total and free testosterone plus the presence of low libido, erectile dysfunction, osteoporosis or facture, or two or more of the following symptoms: sleep disturbance, depressed mood, lethargy, or diminished physical performance.

For this study, the researchers analyzed data on 1,475 randomly selected men enrolled in the Boston Area Community Health (BACH) Survey. The survey tracked subjects between the ages of 30-79 and compiled complete data on factors such as testosterone, symptoms of hormone deficiency, and medications that may impact sex hormone levels. Among all men in the study (mean age 47.3 plus-or-minus 12.5 years), approximately 24 percent had low total testosterone and 11 percent had low levels of free testosterone. Interestingly, while low testosterone levels were associated with symptoms, many men with low testosterone levels were asymptomatic (e.g., among men aged 50 years and older 47.6 percent were asymptomatic).

“Since these men would not likely come to clinical attention,” said Araujo, “it may be important to determine whether there are clinical risks to missing these asymptomatic men with low testosterone levels.” Overall, only 5.6 percent of men in the study had symptomatic androgen deficiency. For those men in the upper range of ages in the study (70 years or older), however, the percentage increased to 18.4 percent.

The researchers predicted that by the year 2025 there may be as many as 6.5 million American men 30-79 years of age with symptomatic androgen deficiency, an increase of 38 percent from year 2000 population estimates.

“This study did not assess whether men with symptomatic androgen deficiency are good candidates for testosterone therapy,” said Araujo. “Well designed randomized placebo-controlled trials would be needed to address the risks and benefits of testosterone therapy.”

The BACH Survey was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (Grant DK 56842). Analyses for the current study were supported through an unrestricted educational grant from GlaxoSmithKline.

A rapid release version of this paper has been published on-line and will appear in the November 2007 issue of the Journal of Clinical Endocrinology & Metabolism, a publication of The Endocrine Society.

Title: Prevalence of Symptomatic Androgen Deficiency in Men

Authors: Andre B. Araujo, Gretchen R. Esche, Varant Kupelian, Amy B. O'Donnell, Thomas G. Travison, Rachel E. Williams, Richard V. Clark, and John B. McKinlay

2. New Treatment Option for Life-Threatening Symptom of Parathyroid Cancer

New research accepted for publication in the Journal of Clinical Endocrinology & Metabolism (JCEM) reveals that the drug cinacalcet HCl (cinacalcet) may effectively reduce the dangerous accumulation of calcium in the blood that typically accompanies parathyroid cancer.

This drug therapy could provide a new and effective medical treatment option for patients with inoperable parathyroid carcinoma (cancer).

“Patients with inoperable parathyroid cancer typically have to contend with extremely elevated levels of calcium in their blood, which can lead to mental confusion, dehydration, kidney damage and ultimately death,” said Dr. Shonni Silverberg of the College of Physicians and Surgeons at Columbia University in New York City and senior author of the study.

Management of inoperable parathyroid carcinoma has been a challenge due to the lack of effective medical therapy. In addition to treating the cancer, doctors also often need to treat hypercalcemia, or excess calcium in the blood, which can be more harmful than the parathyroid cancer itself.

“Until now, the therapeutic choices for patients with inoperable parathyroid cancer have been extremely limited,” said Silverberg. “Cinacalcet offers an important option for treating hypercalcemia in patients with metastatic disease after surgical options have been exhausted.”

Cinacalcet is a drug that mimics how calcium acts on organ tissues. It is used to treat hyperparathyroidism, or elevated parathyroid hormone levels, because it reduces parathyroid cell hormone secretion by binding to the calcium-sensing receptor on parathyroid cells.

The study was conducted at 15 centers in the United States and Europe. Twenty-nine patients with parathyroid cancer were enrolled. The study design included a variable-length titration (treatment with varying doses) phase and a maintenance phase. During the titration phase, cinacalcet was administered to patients until their serum calcium concentration were within normal levels (<10 mg/dL), the dose reached 90 mg, or the patient experienced adverse effects.

During the maintenance phase, dose increases were administered if needed, and doctors were permitted to prescribe treatments deemed necessary to provide adequate supportive care.

Serum calcium was reduced by >1 mg/dL in 62 percent of patients. The greatest reductions in serum calcium were observed in patients with highest baseline calcium levels. Adverse effects of cinacalcet included nausea, vomiting, and headache.

Parathyroid glands are endocrine organs located behind the thyroid gland in the neck. They are necessary for proper bone development, and to control the level of calcium in the blood. The parathyroid glands make parathyroid hormone, which takes calcium from bones so that it will be available in the blood for nerve conduction and muscle contraction.

"This trial is an important milestone for patients suffering from this devastating form of cancer,” said Dolores Shoback, Associate Editor of the Journal of Clinical Endocrinology and Metabolism. “Cinacalcet is the first agent to target the main control switch for parathyroid hormone secretion—the calcium receptor. All prior therapies for this disease work on the bone and patients quickly become refractory to those treatments."

Other researchers working on the study include Drs. Mishaela Rubin and John Bilezikian of Columbia University, Dr. Charles Faiman of the Cleveland Clinic Foundation, Dr. Munro Peacock of the Indiana University School of Medicine, Dr. Dolores Shoback of the Department of Veterans Affairs Medical Center, Dr. Robert Smallridge of the Mayo Clinic College of Medicine, and Drs. Schwanauer, Olson, and Klassen from Amgen, Inc

JCEM is a publication of The Endocrine Society. Dr. Silverberg’s article “Cinacalcet Hydrochloride Reduces the Serum Calcium Concentration in Inoperable Parathyroid Carcinoma” will appear in the October issue of the journal.

3. Maternal Weight Linked to Child Body Composition

New research shows children whose mothers had a high pre-pregnant body mass index or large mid-upper arm circumference in late pregnancy, have a greater fat mass index at age nine years than other children in their age group.

“Increasing numbers of women are now overweight or obese at the start of pregnancy,” said Dr. Catharine Gale of the University of Southampton and co-author of the study. “Reducing the prevalence of overweight or obesity among women before they become pregnant may help break a cycle of obesity from one generation to the next.”

The study followed 216 nine-year-old children whose mothers had previously participated in a study of nutrition during pregnancy. In the previous study, mothers had their height and weight measured in early pregnancy and their mid-upper arm circumference measured in late pregnancy. When their children approached nine years of age, the mothers were contacted and their children were invited to participate in a further study.

The children underwent measurements of height, weight, and body composition. After adjustment for age, birthweight, infant weight gain, duration of breastfeeding, maternal height, smoking and amount of weight gained in pregnancy, a larger maternal mid-upper arm circumference in late pregnancy or a higher pre-pregnant body mass index remained independent predictors of greater fat mass in both boys and girls.

One explanation for these findings is that maternal over-nutrition before and during pregnancy, thought not excessive weight gain, may have a long-term, persisting influence on the adiposity of the child. However, maternally transmitted genetic factors and the effect of maternal lifestyle on that of her child could also explain the results.

A rapid release version of this paper has been published on-line and will appear in the October 2007 issue of the Journal of Clinical Endocrinology & Metabolism, a publication of The Endocrine Society.

Title: Maternal Size in Pregnancy and Body Composition in Children

Authors: Catharine R. Gale, M. Kassim Javaid, Sian M. Robinson, Catherine M. Law, Keith M. Godfrey, and Cyrus Cooper.

4. New Patient Guide on the Management of Maternal Hyperthyroidism Before, During and After Pregnancy Now Available from The Hormone Foundation

In conjunction with The Endocrine Society, The Hormone Foundation has published the "Patient Guide to the Management of Maternal Hyperthyroidism Before, During and After Pregnancy." based on the clinical guidelines of The Endocrine Society. This publication is the second of three parts focusing on thyroid disease in pregnant women. It summarizes who is at risk, the different causes for hyperthyroidism, and special considerations for the management of hyperthyroidism before, during and after pregnancy. The guide will be published in the September issue of The Journal of Clinical Endocrinology & Metabolism and the October issue of Endocrine News. (Part 3 of the patient guide will address maternal thyroid nodules and cancer before, during and after pregnancy.)

To view the patient guide on maternal hypothyroidism visit www.hormone.org.

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Founded in 1916, The Endocrine Society is the world's oldest, largest, and most active organization devoted to research on hormones and the clinical practice of endocrinology. Today, The Endocrine Society's membership consists of over 14,000 scientists, physicians, educators, nurses and students in more than 80 countries. Together, these members represent all basic, applied, and clinical interests in endocrinology. The Endocrine Society is based in Chevy Chase, Md. To learn more about the Society, and the field of endocrinology, visit our web site at www.endo-society.org.