The lack of concrete research has given rise to all kinds of theories, including a sudden drop in the use of hormone-replacement therapy by menopausal women after health warnings in 2002, higher rates of depression among baby boomers or a simple statistical fluke.

At the moment, the prime suspect is the skyrocketing use  and abuse  of prescription drugs. During the same five-year period included in the study, there was a staggering increase in the total number of drug overdoses, both intentional and accidental, like the one that recently killed the 28-year-old actor Heath Ledger. Illicit drugs also increase risky behaviors, C.D.C. officials point out, noting that users’ rates of suicide can be 15 to 25 times as great as the general population.

Jeffrey Smith, a vigorous fisherman and hunter, began ordering prescription drugs like Ambien and Viagra over the Internet when he was in his late 40s and the prospect of growing older began to gnaw at him, said his daughter, Michelle Ray Smith, who appears on the television soap “Guiding Light.” Five days before his 50th birthday, he sat in his S.U.V. in Bloomfield Hills, Mich., letting carbon monoxide fill his car.

Linda Cronin was 43 and working in a gym when she gulped down a lethal dose of prescription drugs in her Denver apartment in 2006, after battling eating disorders and depression for years.

Looking at the puzzling 28.8 percent rise in the suicide rate among women ages 50 to 54, Andrew C. Leon, a professor of biostatistics in psychiatry at Cornell, suggested that a drop in the use of hormone replacement therapy after 2002 might be implicated. It may be that without the therapy, more women fell into depression, Dr. Leon said, but he cautioned this was just speculation.

Despite the sharp rise in suicide among middle-aged women, the total number who died is still relatively small: 834 in the 50-to-54-year-old category in 2004. Over all, four of five people who commit suicide are men. (For men 45 to 54, the five-year rate increase was 15.6 percent.)

Veterans are another vulnerable group. Some surveys show they account for one in five suicides, said Dr. Ira Katz, who oversees mental health programs at the Department of Veterans Affairs. That is why the agency joined the national toll-free suicide hot line last August.