Appetite Hormone Key to Women's
Leptin, the hormone best known to control
appetite, also appears to play a major role in fertility and bone
development in women.
A small, new study finds synthetic
injections of the hormone can help young women whose naturally
low levels of leptin left them thin and prone to osteoporosis,
broken bones, and reproductive problems.
Low doses of leptin restored hormonal
balance, improved bone density, and began menstrual cycles again,
according to the study, which appears in the Sept. 2 issue of
the New England Journal of Medicine.
The researchers also suspect that
leptin is involved in eating disorders, although that wasn't tested
in this research.
Leptin, which was discovered 10
years ago, is a protein that helps regulate body weight, metabolism
and reproductive function, and it has been linked to appetite
and weight regulation. Leptin plays another role as well, signaling
the brain and other organs to dangerously low energy availability.
Leptin is produced in fat tissue
and secreted into the bloodstream in proportion to the amount
of energy stored in fat, explained lead researcher Dr. Christos
Mantzoros, director of human nutrition research at Beth Israel
Deaconess Medical Center and an associate professor of medicine
at Harvard Medical School. Leptin tells the brain how much energy
the body has available, he explained.
Levels of leptin regulate key body
functions that depend on having adequate energy, including reproduction,
metabolism and bone formation, Mantzoros said. "We are talking
about three related but distinct disease states," he added. "One
is anorexia nervosa."
The second group is women who exercise
a lot, "such as athletes and dancers, who lose fat mass, and use
more energy than the energy than they take in. These women have
no periods, low estrogen levels, abnormal thyroid levels, and
low levels of growth hormone," he said.
This condition, called hypothalamic
amenorrhea, leads to osteoporosis and infertility. "Despite exercise,
these women have osteoporosis, usually unbeknownst to them," Mantzoros
An even larger group is extremely
thin women who have very mild abnormalities and are infertile.
"The common thread in all these conditions is energy deficiency,"
To find out what causes these abnormalities,
Mantzoros' group looked at leptin levels in female athletes with
hypothalamic amenorrhea. The researchers treated six women with
low doses of leptin for three months to bring their hormonal levels
into the normal range.
Another group of six women were
given no treatment, but were observed for almost nine months.
"In the women not treated, nothing
changed," Mantzoros said. "But in the women who were treated,
all the hormone levels that were abnormal improved. Their estrogen
levels went up, thyroid levels improved, and growth hormone levels
The women also started having menstrual
periods after not having had them for an average of 5.5 years,
Mantzoros said, adding that bone density improved.
The impact of the study is that
it explains why women develop these conditions, Mantzoros said:
"Because leptin is missing."
The results of the study also open
up new treatment options. Mantzoros's team is starting a larger
trial to find out if leptin is safe and effective for treating
hypothalamic amenorrhea to prevent osteoporosis and normalize
all the hormone levels.
Moreover, in extremely thin women
who cannot reproduce, low-dose leptin might make conception possible
without having to resort to in vitro fertilization, Mantzoros
Mantzoros cautioned that leptin
therapy is not appropriate for treating women with anorexia nervosa.
"For the first time we know the
causes of these problems, and knowing the cause we can effectively
treat it," Mantzoros said.
The discovery should spur more
research into the disorder, said Dr. Rexford S. Ahima, an assistant
professor of medicine at the University of Pennsylvania School
of Medicine. "Hypothalamic amenorrhea, a disease that was first
described in the 1940s and was poorly understood for decades,
may finally benefit from a rebirth of investigation leading to
rational therapy," Ahima wrote in an accompanying article.
"Prospective demonstration that
leptin replacement for women who are in chronic negative energy
balance (and thus lack sufficient adipose tissue) restores menstrual
cycles and bone density has not been accomplished before," added
Dr. Tamas Horvath, an associate professor of obstetrics and gynecology
and neurobiology at the Yale School of Medicine.
The paper "shows a critical role
for leptin in these processes," he added.
Horvath is not sure how women receiving
leptin replacement will do over the long term. "Would the quasi-fooled
physiological response of energy re-organization have a negative
impact on functioning of other tissues, such as the heart, liver
kidney and brain?" he wondered.
The study was funded by grants
from the National Institutes of Health, Harvard University, and
Amgen, which makes the genetically engineered hormone.
Read about infertility at the American
Society of Reproductive Medicine.
Reference Source 101
September 2, 2004