Delay in Diagnosis of Menopause-like Condition in Young Women Linked to Low Bone Density

Women Who Don’t Receive Treatment May Risk Osteoporosis

Women and young girls who experience delays in diagnosing a premature, menopause-like condition face increased risk of low bone density, according to new research by scientists at the National Institutes of Health. A delay in diagnosing the condition, called primary ovarian insufficiency, may make women more susceptible to osteoporosis and fractures later in life, the researchers concluded.

Delays in diagnosis are common because the main symptom, irregular or stopped menstrual periods, is often disregarded by women and their doctors, the researchers said. The researchers also found that the beginning of menstrual irregularity before age 20 was a strong risk factor for lower bone density. The teen years are a critical period for developing healthy bones.

The minority patients in the study were more likely to have low bone density than were white patients in the study. African-American women were less likely to consume sufficient calcium than were white women and more likely to have low vitamin D levels. Asian women were less likely than white women to take the replacement hormones prescribed as a treatment for the condition.

“For years, primary ovarian insufficiency has been known to put women at risk of low bone density,” said Duane Alexander, M.D., director of NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). “The new study helps explain why some women with the condition are more likely to develop low bone density. It also provides strong evidence that by diagnosing the condition early, replacing deficient estrogen, and getting adequate calcium and vitamin D, these women can protect their bones from weakness and fractures.”

Primary ovarian insufficiency occurs in girls and women younger than 40 when their ovaries stop working normally. Because their ovaries no longer release eggs or produce estrogen, girls and women with primary ovarian insufficiency experience infertility and develop symptoms similar to those of menopause, including loss of regular menstrual periods, and hot flashes. The symptoms may be lessened or relieved by replacing estrogen.

Estrogen also helps the bones to absorb calcium. Women who enter normal menopause after age 40 experience some degree of bone loss. However, the bone loss may be much worse for women who stop producing estrogen at much younger ages, especially if they do not take replacement estrogen.

The condition occurs in 1 out of 100 women by age 40. In 90 percent of the cases, the cause is unknown.

Lawrence Nelson, M.D., head of NICHD’s Unit on Integrative Reproductive Medicine, is the senior author on the study, which appears on line in the Journal of Clinical Endocrinology & Metabolism.

Dr. Nelson and his coworkers sought to determine which factors put girls and women with primary ovarian insufficiency at greatest risk of low bone density.

“Bone density is like a woman’s bank account of bone,” he said. “The more women build up and maintain their bone density when they’re young, the better off they will be when they’re older.”

The scientists compared 442 patients to 70 volunteers with normally functioning ovaries, as well as to the records of 353 women who had participated in a large study called the Third National Health and Nutrition Examination Survey. The researchers found that women who had primary ovarian insufficiency had 2 to 3 percent lower bone density than did women without the condition.

“Later in life these women could be at increased risk of osteoporosis or fractures beyond the risk posed by normal menopause,” Dr. Nelson said.

The researchers looked at factors that predisposed the women to low bone density. These factors included low vitamin D levels, not taking estrogen, low intake of calcium, and not getting regular exercise.

The researchers found that the women with low bone density tended to experience a delay of more than a year between their first irregular menstrual period and receiving a diagnosis of primary ovarian insufficiency. The patients’ average time between first irregular period and diagnosis was around 4 years.

“Our research has shown that the menstrual cycle actually is a marker of general health in women,” Dr. Nelson said. “A delay in diagnosis may be causing women harm.”

From other research, Dr. Nelson has concluded that women with primary ovarian insufficiency should take estrogen, eat well, and exercise regularly. He published an article earlier this year, in the Feb. 5 New England Journal of Medicine, outlining a comprehensive plan for diagnosing and treating the condition. A release describing the plan is available at

Dr. Nelson said that he was surprised by the finding that the African-American women in the study were more likely to have lower bone density than were white women. In general, African-American women are at lower risk for osteoporosis than are white women. He added that making sure to consume adequate calcium and vitamin D—either by modifying dietary habits or taking supplements—would probably reduce the bone thinning seen in this group of women.

Other authors of the paper were: Vaishali Popat, Vien Vanderhoof, and James Troendle of NICHD; Karim Calis, James Reynolds, and Nancy Sebring of NIH’s Mark O. Hatfield Clinical Research Center; and Giovanni Cizza of the National Institute of Diabetes and Digestive and Kidney Diseases.


The NICHD sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visit the Institute’s Web site at

The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical, and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit

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