Drugs seem to help some thinning pates, and a "baldness cure" may yet be found, but for now many of us will just keep on losing it

Author: By Judy Foreman, Globe Staff

Date: MONDAY, December 2, 1996

Page: C1

Section: Health and Science

At first, her part just seemed to be getting wider. Soon, whenever she shampooed her hair, she'd wind up with 15 or 20 strands in her hands. Eventually, her hair became so thin it was hard to style it in a way that covered her head.

``When this happens to people, especially to a woman, it's extremely emotionally distressing and socially crippling,'' she says. ``I went to doctors. I tried a lot of phony treatments. I cried a lot. It was pretty devastating.''

Then, several months ago, she spotted an ad in the Yellow Pages for a New York doctor touting a new way to make hair grow.

It turned out to be a hair spray made from two drugs already approved by the Food and Drug Administration: minoxidil, the active ingredient in Rogaine, an over-the-counter potion that boosts hair growth in some people, and tretinoin, the chief constituent of Renova and Retin A, prescription-only drugs that combat wrinkles and acne.

Never mind that the doctor's homemade concoction, though not illegal, had never been tested in controlled clinical trials, so there is no solid proof that it's safe, and that it works.

Never mind that the doctor isn't a dermatologist, the type of medical specialist who usually treats hair growth problems.

Never mind even that the physician, Dr. Adam LewenbergCQ, was using an idea originally developed by someone else, Louisiana biochemist and use patent holder Gail S. BazzanoCQ, who has a tale to tell of running afoul of a giant cosmetics company in her quest to get her hair growth product on the market.

Like many of America's 20 million balding women and 40 million balding men, all that Beth Stein wanted was more hair.

Until recently, at least, that has been a quixotic quest.

Though most of us couldn't care less until something surprising happens -- like waking up one day and realizing a once-robust hairline is drifting out of sight -- our hair grows, falls out and grows again in a steady cycle throughout life.

In the growth or ``anagen'' phase, scalp hair grows for about two years, says Dr. Barbara Gilchrest, chairman of the dermatology department at Boston University School of Medicine.

If you can grow hair down to your knees, it means you have an unusually long anagen phase; if you can't grow it past your collar, you've got a short one. (The reason eyebrows never get very long -- in case you were pulling your hair out over that one -- is that eyebrow hairs have a very short, 2-month cycle.)

At the end of the anagen phase, the hair follicle, from which the hair shaft grows, enters a short ``catagen'' phase in which it shrinks back to a smaller size. In the third or ``telogen'' phase, the follicle just sits dormant for several months.

Eventually, the hair gets loose, falls out, and the cycle begins again. At any given moment, about 90 percent of hairs on the scalp are in the growing phase and 10 percent are resting -- and in some lucky souls, this process continues throughout life.

But in many men and women, hair follicles eventually wimp out, probably because of the effect of male hormones called androgens. New evidence suggests a female hormone, estrogen, may be involved, too.

In men, who often have what's called ``male pattern baldness,'' thinning starts at the forehead and works its way back, sometimes merging with another bald spot that begins at the crown of the head. Women don't usually have creeping hairlines, but wind up with thin spots or very sparse hair all over.

With each hair cycle, male hormones activate receptors in the follicle, slowly turning large follicles into small ones that produce only wispy hairs. This process is especially pronounced in people who are genetically predisposed to balding.

``It's as if the factory wears out,'' says Dr. Robert Stern, a dermatologist at the Beth Israel Deaconess Medical Center. ``The factory starts to turn out an inferior product, then it just goes out of business.''

Still, there is enormous variation in the degree of hair loss in both men and women. At the same hormone levels, for instance, some men are as bald as the proverbial billiard ball, and some as hairy as the Biblical Samson on a good day.

Eunuchs, by the way, always have lots of hair because they have been castrated and have very low levels of male hormone, a link that was discovered almost 50 years ago in a chance comparison of two twins.

One brother was mentally ill and confined to an institution, where he was castrated. Years later, the other brother went to visit and doctors were shocked -- the institutionalized man had a full head of hair while his brother was bald, says Dr. Michael Holick, chief of the BU endocrinology, nutrition and diabetes department.

When the first brother was given hormones, he went bald, too.

Because most guys consider castration a high price to pay for a manly mane, researchers have been hustling to find other options for both men and women with hair loss. Here's what they're coming up with:

- Rogaine. Since February, Pharmacia & Upjohn has been selling its 2 percent minoxidil product over the counter, though results are often less than dramatic. About 25 percent of men and 20 percent of women can achieve what the FDA calls ``meaningful'' hair for $1 or so a day.

Minoxidil, which may work by increasing blood flow to the scalp, seems to help most those who need it least -- people who are thinning, but not yet bald. It doesn't do much for ``frontal regression,'' the backward creep of the hairline.

And if you stop using it, you lose whatever gains you made, ``which is good for Upjohn but sort of a bore for patients,'' notes Stern of Beth Israel Deaconess.

- Propecia. This new anti-balding drug, still unapproved by the FDA, is a weaker form of Proscar, Merck's anti-prostate enlargement drug, also called finasteride.

Finasteride combats hair loss by blocking the conversion of the male hormone testosterone to DHT, or dihydrotestosterone, which turns big, healthy hair follicles into wimps.

In a six-month trial of Propecia tablets in 466 men aged 18 to 35, in which neither the men nor their doctors knew whether they were getting the drug or a placebo, the majority of those on the drug had ``clinically significant'' growth, says Merck, which hopes to market the drug soon.

- Estrogen blockers. So far, this is just an idea -- but an intriguing one. In a study, Robert C. Smart, a molecular toxicologist at North Carolina State University, found that blocking estrogen makes hair grow faster than normal in mice.

``Estrogen keeps the hair follicle in an inactive state,'' says Smart, who adds that by spreading an anti-estrogen cream on the skin, ``you can make an inactive follicle active.''

Would it work in people? Nobody knows, though Dr. Ulrike Lichti, a hair follicle investigator at the National Cancer Institute, notes that ``the hair cycle in mice and humans is very different.'' And estrogen is important for healthy skin, so spreading an anti-estrogen cream on the skin could be harmful.

- Parathyroid blockers. Researchers have long known that a substance called parathyroid hormone related peptide (PTHRP) turns off cell division in skin cells, including the thousands of cells that make up hair follicles, says Holick.

So his team has been trying to find ways to block PTHRP in order to turn cell division back on, and thus encourage hair follicles to grow. So far, he says, he has found one experimental PTHRP blocker that makes resting hair follicles go into the growth phase and stay there longer than normal, at least in mice. Tests will soon begin in people.

- Gene therapy. Researchers at AntiCancer, Inc. in San Diego have shown they can use a cream made of liposomes -- small fat bubbles -- to deliver genes, like those for hair color, into hair follicles in mice. Nobody has found the gene or genes that control balding, and AntiCancer isn't looking. ``But if such a gene is discovered,'' says company biochemist Andrew Perry, ``we can get it into the hair follicle.''

- Minoxidil-tretinoin. In New York, business is booming for Dr. Adam Lewenberg, who says his ``proprietary'' hair spray is a combination of 2 percent minoxidil and 0.025 percent tretinoin.

The idea of mixing the two drugs makes sense to some dermatologists, who say that tretinoin might increase the penetration of minoxidil into the scalp, giving it more punch.

So far, Lewenberg says he has sold, for $180 a month, his concoction to more than 2,000 patients, and that 90 percent have had improvement in hair quality after three months.

That's hardly a scientific study, but Beth Stein, one of his patients, says she's pleased that at least her hair has stopped falling out. She calls her results `encouraging. . . but not dramatic.''

Ron Maloney, 39, the owner of a real estate appraisal company in Pelham, N.Y., has been using Lewenberg's hair spray several times a day for seven months. Before that, he had tried Rogaine, Proscar and another chemical product -- all to no avail -- and even considered scalp-reduction surgery, to make the hair he had left cover more of his head.

Then he tried Lewenberg's hair spray and is delighted with the results: ``It's the only thing I've ever had that works.''

All of which is not exactly music to the ears of two New Orleans researchers, Dr. Nia Terezakis, a dermatologist in private practice, and Gail Bazzano, a biochemist and president of the Alyzan Corp. They have spent more than a decade developing and studying hair growth with the minoxidil-tretinoin combo.

Years ago, Bazzano licensed her minoxidil-tretinoin technology to L'Oreal, the European cosmetics giant, to develop and market. Nothing happened, so Bazzano sued for breach of contract. Several weeks ago, she won her case, and $1.2 million from L'Oreal. ``I'm going to develop it now,'' she says.

Spokesmen for Pharmacia & Upjohn, maker of minoxidil, and Ortho Dermatological, maker of the tretinoin products, would not say whether their companies are also trying to develop the combination treatment. For safety reasons, the companies take a ``Don't try this at home'' line, urging consumers not to try mixing the two drugs themselves.

But some people are reportedly doing just that -- with unclear results. Some even try to make try to make minoxidil stronger by letting it evaporate or by putting it in a microwave, an unwise idea because minoxidil can cause side effects, including chest pains, rapid heart beat, dizziness, sudden weight gain and swollen hands or feet.

At the very least, if you really want to try mixing minxodil and tretinoin, consult a dermatologist. If he or she agrees, get a druggist to ``compound'' the combination.

But if nothing that you've tried for hair growth works and you find yourself still pining for the puffy plumage of youth, take heart. Things may be better when your kids are your age.

With the new molecular understanding of how the hair follicle functions, ``there really is hope,'' says Holick. ``Within a decade or two, balding could be a thing of the past.''