Recombinant human growth hormone (rhGH) can add inches to theheight of a child stunted by lack of natural GH produced in his or herpituitary gland. It's also FDA-approved to treat chronic renalinsufficiency, and _ still experimentally _ Turner's syndrome. (SeeBioWorld Today, Oct. 26, 1995, p. 1.)

As reported at the international AIDS conference in Yokahama twoyears ago, rhGH is being tried to counter the body-wasting effects ofHIV infection.

Off the record, athletes allegedly shoot up the hormone as a blood-booster conferring short bursts of strength and endurance.

And health food stores tout the virtues of growth hormone as averitable "Fountain of Youth" to restore prime-of-life vigor andshape to aging minds and bodies.

These purveyors of the Faustian bargain often buttress their promisesto roll back the years, and repair the ravages of old age, by evoking a1990 article in the New England Journal of Medicine titled "Effectsof human growth hormone in men over 60 years old." Its author,Daniel Rudman, of the Medical College of Wisconsin, in Milwaukee,administered the recombinant drug for six months to 12 men 61 to 70years of age .

It increased their lean body mass by 9 percent, and decreased adiposetissue mass by 15 percent. On the basis of this data, obtained in anunblinded trial, Rudman concluded that diminished secretion ofsomatomedin _ a hormonal measure of GH _ accounts in part forthe somatic changes of aging. These he called "somatopause," themale counterpart of menopause.

Since then, gerontologists have waited for the other shoe to drop,namely, a double-blinded, placebo-controlled clinical trial ofexogenous human growth hormone's presumed beneficial effects onthe minds and bodies of old men.

They got it in the April 15, 1996, issue of the Annals of InternalMedicine. The paper's title tells the story they, and the medicalcommunity at large, had hoped not to hear: "Growth hormonereplacement in healthy older men improves body composition but notfunctional ability."

Its senior author, endocrinologist Carl Grunfeld, co-directs thespecial diagnostics and treatment unit at the Veterans Affairs MedicalCenter, in San Francisco.

"Rudman was a very well respected clinical investigator," Grunfeldtold BioWorld Today, and his was a seminal study. But suchstudies," he added, "need to be followed up by double-blinded,placebo-controlled trials. Our paper was one of what I think will beseveral saying that growth hormone is not a magic elixir.

"While the legitimate medical world was waiting for these studies,"Grunfeld continued, "non-medical organizations in several countries,particularly Mexico _ which sells rhGH at high prices _ promotedit in the lay literature as a fountain of youth, supposed to return yourvigor to that of a young person."

Wanted: Oldsters To Check Out Youth Drug

Grunfeld, and the paper's first author, clinician Maxine Papadakis,placed advertisements in San Francisco papers inviting Bay Areasubjects as volunteers to assess the effects of rhGH treatment.

"We recruited 56 healthy, ambulatory community-dwelling men olderthan 69 years of age, and ranging from 70 to 85," Grunfeld said.Treatment consisted of Nutropin, the trademarked version of rhGH,and identical vials of a placebo, both supplied by Genentech Inc., ofSouth San Francisco.

Results of the six-month regimen were paradoxical.

On the one hand, the 26 men who self-injected Nutropin three times aweek out-scored the 26 on placebo in most parameters of the trial:

* Their lean body mass increased 4.3 percent on average, butdecreased 0.1 percent in the placebo cohort.

* Their fat mass dropped 13.1 percent and 0.3 percent in the placebogroup.

* Bone mineral content went up 0.9 percent, and down 0.1 percentfor placebos.

* Muscle-strength changes were similar in both groups.

* One test of cognitive function favored the active-drug recipientsover the placebo panel by 8.5 seconds improvement to 5.0 secondsdeterioration. But in another type of measurement, placebo won byimprovement of 0.2 against decline of 0.4

On the other hand, all these fine-print results aside, Grunfeld's paperconcluded: "Despite these improvements in body composition,treatment with growth hormone was not associated with a statisticallysignificant improvement in muscle strength, systemic endurance orcognitive function."

What's more, the rhGH loading came at the price of bothersome,though not life-threatening, side effects. More than one-fourth of the52 men who completed the trial required lowering of the rhGHdosage to abate leg and foot edema, diffuse joint pain (for whichthere was no clinical evidence of inflammation), hand stiffness,tender breasts and malaise.

Placebo Controls Got Side Effects Too

All told, 77 percent of the active drug recipients complained of thesesymptoms, but so _ curiously _ did 46 percent of the placeborecipients. All these medical toxicities disappeared at the end of thetrial.

"We are still analyzing further data from this original study,"Grunfeld observed. "So far, we have found no clinically significantimprovement in function, and significant incidence of side effects.Therefore, at least in the elderly who are not totally growth-hormonedeficient, we don't think growth hormone replacement therapy canfix that.

"We did not get a dramatic response. We did get a change in bodycomposition, but that's not the question. The question is: `Is what wegot what we would have liked to get to help the elderly?'"

He summed up: "Here's a controlled trial that serves to counter thepeople who claimed that growth hormone replacement could restoretheir vigor. It says GH does not return you to being a 24-year-old,which is what everyone wants." n

-- David N. Leff Science Editor

(c) 1997 American Health Consultants. All rights reserved.