PROPECIA (ORAL FINASTERIDE) IN THE TREATMENT OF ALOPECIA ANDROGENETICA & INSTRUCTIONS FOR USE

Reduces 66% + - of DHT in blood serum
(Click on Azelaic Acid for purposes of comparison)

Baldness drug may reduce prostate cancer risk: But it could trigger more aggressive form in other cases
(Please scroll to bottom of page for article on this topic)

Propecia can only be dispensed or prescribed to new Regrowth patients after an in-office consultation has taken place with a Regrowth physician.

FINASTERIDE

There is no doubt that androgens are intimately involved in causing male pattern baldness. Famous castrati in the time of Handel and Teleman not only retained strong soprano voices, but were assured of a lifetime of beautiful locks. Hamilton, known popularly for the Hamilton Scale of grading male pattern baldness, noted that castration after the onset of puberty arrests the progression of human alopecia (1). On the other hand, the administration of therapeutic doses of testosterone to hypogonadal adult males results in the loss of scalp hair (whereas there is no noticeable change in the scalp hair of normal men).

The active androgen in the balding scalp appears to be dihydrotestosterone, which is produced from testosterone through the activity of the 5-alpha-reductase enzyme (2). Biopsies and biochemical analyses corroborate the elevated 5-alpha-reductase levels in the frontal scalp of balding men and the lack of hair loss in human males with 5-alpha-reductase deficiencies.(3) In fact, the levels of 5-alpha-reductase is usually 4 times higher in balding areas than the occiput, which is not affected in male pattern baldness.

Recently, two isoenzymes of 5-alpha-reductase have been identified in human tissue. The type 1 isoenzyme is found in scalp skin, whereas 5-alpha-reductase of type 2 is the predominant form in the prostate (4).

Propecia, also known as 1 mg. finasteride, is a potent inhibitor of human 5-alpha-reductase, yet devoid of antiandrogen activity (5) itself, so the circulating levels of testosterone are not affected. Finasteride, manufactured and marketed by Merck Pharmaceutical as Proscar, has been shown to be effective in the treatment of benign prostatic hyperplasia. At the therapeutic dose of 5 mg/day, finasteride lowers serum dihydrotestosterone levels in men by 65-80% compared to baseline levels and decreases intraprostatic levels of dihydrotestosterone by 85% compared to placebo (6). Finasteride has been approved for use in treatment of BPH since 1994. In January of 1998 the FDA in the U.S.A. approved Propecia, a 1 mg. tablet of finasteride by Merck for the treatment of alopecia androgenetica.

Since the pathogenesis of balding in the stumptail macaque monkey and human appears to be similar and partially reversible in both species by long term use of topical minoxidil solutions, clinical trials were performed in 1991 in these primates to evaluate the hair growth effects of oral administration of finasteride alone and in combination with topical minoxidil (7). The results showed that the combination of finasteride and minoxidil generated significant augmentation of hair weight (additive effect) compared to either drug alone. Furthermore, folliculograms of scalp biopsy tissue showed a higher frequency of late anagen follicles in subjects treated with 5% minoxidil than in those administered a 2% concentration (7). Analysis of the data confirms that using minoxidil and finasteride together is significantly better than using either alone, and that minoxidil in higher concentrations is more effective than at lower concentrations.

At the 1995 American Association of Dermatology Meeting in New Orleans, results from a one year, double-blind, randomized, placebo-controlled study with finasteride in the treatment of male pattern baldness were presented. Men taking oral finasteride (5 mg/day) had significantly increased hair counts and significantly improved clinical change from baseline as assessed by multiple parameters including patient self evaluation. There were few drug related side effects reported, with similar numbers in both finasteride and placebo groups.

At the same meeting, results from a dose-range-finding study were presented, evaluating finasteride at doses of 0.01, 0.05, 0.2, 1 and 5 mg/day. A six week trial measured concentrations of scalp skin and serum dihydrotestosterone. Surprisingly, other than the group taking 0.01 mg/day, no significant differences between the doses were seen. However, significant differences were documented between the groups that received finasteride (excluding those receiving 0.01 mg/day) and the group that received placebo. It was determined that a low dose of oral finasteride will be used for further studies in the treatment of male pattern baldness.

At the annual meeting of the American Academy of Dermatology during March, 1997 in San Francisco, the Phase III clinical trials were presented for Propecia, 1 mg. finasteride. The tests evaluated 1,553 men with male pattern baldness in placebo controlled studies for one year.

According to Keith Kaufman, M.D., director of clinical research at Merck & Co., Inc., there was a 107-hair improvement in men taking Propecia (1mg finasteride) compared to those receiving placebo. Scalp hair growth was measured by counting hairs in a 1 inch diameter circle of active hair loss at the vertex. The increased hair growth achieved with 1mg finasteride was evaluated by the patients as well as by clinical investigators and by review of patient photographs by a panel of dermatologists with expertise in hair loss. By all parameters, treatment with oral daily 1mg doses of finasteride demonstrated improved hair growth. Overall improvement was seen as early as three months with continued improvement over the 24 month trial.

The 1mg daily oral doses of finasteride were generally well tolerated as side effects were reportedly uncommon. Safety was evaluated in more than 3200 men through clinical and laboratory monitoring. Ironically, discontinuation of therapy in Phase III trials due to adverse experience occurred in a higher percentage in the men on placebo (2.1%) than in the men treated with Propecia (1.7%). According to Merck, less than 2% of men experienced decreased libido. Less than 1.5% of men had difficulty achieving an erection. And, less than 1% of men complained of a decrease in the amount of semen. According to Dr. Kaufman, these side effects resolved in men who discontinued therapy with Propecia and, in fact, in many who continued therapy with Propecia. It should be noted that this data was supplied by Merck & Co., not by Regrowth.

The concentration of dihydrotestosterone in the serum is decreased by approximately 60% in patients taking 1mg of finasteride daily. Since finasteride inhibits a key factor responsible for miniaturization of scalp hair follicles, this allows for a reversal of the balding process.

Subsequent reports from Merck & Co., Inc. demonstrate that daily doses of 1mg finasteride is also effective at halting hair loss. Evaluation at the end of a one year study showed that only 14% of patients on Propecia lost hair, as opposed to 58% of patients on placebo. There was continued improvement in patients taking 1 mg. finasteride over 24 months.

More recent results proved that under certain conditions, finasteride can be successful in somewhat reversing frontal hair loss, although less effective than at the vertex. This additional information is encouraging to many patients who are disappointed in the limited ability of minoxidil, when used alone, to stimulate frontal hair growth. The combination therapy has been effective for many patients.

The use of Propecia (finasteride) still allows a significant amount of scalp DHT around the hair follicles. In fact, 5 mg of finasteride daily lowers the scalp DHT by approximately 38% without providing any additional protection from the residual DHT.

That means the scalp still has 62% of the baseline DHT plaguing the follicles. A small reduction of DHT helps some. But finasteride treatment is ineffective for others, and is generally only helpful for frontal loss when the patient also uses minoxidil. Click on Azelaic Acid for purposes of comparison.

When you are getting a physical examination or are having laboratory tests on your blood, inform your doctor that you are taking finasteride.  Finasteride will decrease the PSA (Prostate Specific Antigen) level by approximately 50%.  Assessing the PSA level is a screening test for possible prostate cancer. 

Richard Lee, M.D. 

 

(1)Hamilton JB. Male hormone stimulation is prerequisite and incitant in common baldness. Am J Anat. 71:451-80, 1942

(2)Ebling FJG. Hair follicles and associated glands as androgen targets. Clin Endocrinol Metab. 15:319-39, 1986

(3)Bingham KD, Shaw DA. The metabolism of testosterone by human male scalp skin. J Endocrinol. 57:111-21, 1973

(4)Jenkins, Anderson S, Imperato-McGinley J, Wilson JD, Russell DW. Genetic and pharmacological evidence for more than one human steroid 5-alpha-reductase. J Clin Invest. 89:293-300, 1992

(5)Stoner E. The clinical development of a 5-alpha-reductase inhibitor, finasteride. J Steroid Biochem Mol Biol. 37:375-378, 1990

(6)Gormley GJ, Stoner E, Bruskewitz RC, et al. The effect of finasteride in men with benign prostatic hyperplasia. N Engl J Med. 327:1185-1191, 1992

(7)Diabi AR, Mulholland MJ, Shull KL, Kubicek MF, Johnson GA, Schostarez HJ, Brunden MN and Buhl AE. Hair Growth Effects of Oral Administration of finasteride, a steroid 5-alpha-reductase inhibitor, alone and in combination with topical minoxidil in the balding stumptail macaque. J Clin Endocrinol Metab. 74:345-350, 1992

INSTRUCTIONS FOR USE:

Propecia will not work faster or better if you take it more than once a day or if you increase the dosage.

 

 Understandably, there have been many questions asked by Regrowth patients in regards to the following article:

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Baldness drug may reduce prostate cancer risk: But it could trigger more aggressive form in other cases

Wednesday, June 25, 2003 Posted: 9:21 AM EDT (1321 GMT)

(CNN) -- A study released Tuesday indicates that a drug used to treat male pattern baldness reduces the odds of getting prostate cancer by about 25 percent.

But there's some bad news: The same study seems to show that if a man taking finasteride does get the disease, the drug appears to increase his chance of getting a more aggressive form.

"Finasteride is the first drug found to reduce the risk of prostate cancer," said Dr. Ian Thompson of the University of Texas Health Science Center at San Antonio, the study's lead author. "The drug worked for men at low risk for prostate cancer, as well as those at high risk."

The National Cancer Institute estimates that if 1,000 63-year-old men are tracked, after seven years, 60 of them would develop prostate cancer, with 18 of those men suffering with high-grade tumors, which spread quickly.

If the same men took finasteride for seven years, only 45 would get the cancer, but 22 would have the more aggressive tumors.

A low-dose version of finasteride used to treat hair loss is marketed under the trade name Propecia, while under the name Proscar it's sold as a treatment for enlarged prostates.

In the study, which was funded by the National Cancer Institute and published in the online version of the New England Journal of Medicine, researchers at 221 sites nationwide followed nearly 19,000 men older than 55 for seven years.

About half of them were assigned at random to take either finasteride, a drug that lowers male hormone levels, or a placebo.

By the end of the trial, those taking the drug reduced their risk of prostate cancer by nearly 25 percent over those on placebos.

Mortality in both groups was the same: Five in each group died of prostate cancer.

Promoter of mean types of cancer?

But researchers were not convinced that men should take the drug to prevent the disease, which, after skin cancer, is the most common form of cancer among men. While the men who took finasteride were diagnosed with fewer cases of the disease, they had more high-grade prostate cancers, which typically are more aggressive than other forms.

In all, 6.4 percent of the men on finasteride had high-grade tumors, versus 5.1 percent of men on placebos.

The reason for that disparity was not clear. Thompson said finasteride may result in the development of more aggressive tumors either by preventing only low-grade tumors or by making the prostate gland more favorable to aggressive tumors.

Dr. John Wasson, director of the Center for Aging at Dartmouth Medical School in Hanover, New Hampshire, and who served on the study's safety monitoring committee, said the tumor findings raised a number of questions: "What really is finasteride doing here? Is it a promoter of mean types of cancer, or a suppresser of meaningless types?"

The study was stopped a year earlier than planned because it was determined that the extra time was unlikely to yield new information. In addition, Wasson cited concerns over the apparent increased risk of more aggressive tumors.

Though the study is a major step forward, men should carefully weigh their options before opting to take the drug as a preventive measure, Dr. Harmon J. Eyre, chief medical officer of the American Cancer Society, said in a statement.

"There are still some important unanswered questions, especially regarding side effects, whether it can benefit men at increased risk, especially African Americans, who are twice as likely as white men to die of prostate cancer, and the mechanism by which men taking the drug develop higher grade tumors."

Other side effects

 Despite the concerns, Dr. Nabil Khawand, a physician at Washington Hospital Center, said he would leave the decision to his patients. "I will tell him the result of the study and I will give him the option, whether he wants to be on it or he doesn't want to be on it."

Apparent side effects went beyond tumor aggressiveness. Men taking finasteride were more likely than men on placebo to experience sexual side effects such as impotence.

But men taking the placebos were more likely to be diagnosed with enlarged prostate and urinary problems.

This year, prostate cancer is expected to be diagnosed in more than 200,000 men and kill about 29,000 in the United States. It is typically a slow-growing cancer and most of the men who are diagnosed with it go on to die of something unrelated, even if they undergo no treatment for it.

For young men using the drug to promote hair growth, "I certainly wouldn't want to be taking a drug that potentially promotes cancer of the mean types," Dartmouth's Wasson said. "First, do no harm, that's the bottom line with any drug or treatment ... if you're a young guy, you should really be concerned about finasteride."

 He predicted the study results would lead the Food and Drug Administration to take a fresh look at the safety data on the drug, which is made by Merck and requires a prescription. No one from the agency was immediately available to comment, and a call to the drug maker was not immediately returned.

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Yes, there is cause for concern, but only because Propecia and Proscar are the same medication. The results of a study using a dosage of finasteride five times greater than the dosage recommended for patients with MPB are not applicable. Nor can the statistics be mathematically extrapolated to a different dose.

The statement that best summarizes our thoughts in regards to this article is, "Doctors expressed hope that they will be able to offer more specific guidelines about using the drug after they examine their data."

The association of finasteride and prostate cancer has been reported in an earlier article from USC, which was not reassuring.

Here is a copy of a response to a patient:

"You're probably asking this question because of the report earlier this month (August 1988) of a study from USC/Norris Cancer Center that suggested that finasteride not only does not help prevent prostate cancer, but may, in fact, promote it. They studied 52 men who had an elevated PSA, but no evidence for prostate cancer. The half who were treated with finasteride developed prostate cancer at a much higher rate than did the half that had placebo treatment. (www.pslgroup.com/dg/91D2A.htm) However, it's difficult to draw conclusions from this study. Men who already have elevated PSA levels do not reflect the general population.

I had a long and informative conversation this morning with Barbara Mathes, M.D., who is a researcher and coordinator at Merck Pharmaceuticals. It is the contention of Dr. Mathes that the sampling from the USC/Norris study was too small and that it was not a
representative group. Furthermore, since the finasteride would have shrunken the prostate, biopsies in that group would be expected to have a higher positive yield."

Meanwhile, if you already using finasteride with satisfactory results and without side effects, we would recommend that you continue to use finasteride as a treatment for MPB. If you want to discontinue finasteride in favor of proven and safe topical medications or if you are not currently taking finasteride and wish to decrease the amount and/or activity of DHT in the scalp, use a topical medication such as azelaic acid, topical spironolactone or ketoconazole shampoo.

Under no circumstances would I recommend switching to the use of dutasteride.

Richard Lee, M.D.
Consulting Physician
Regrowth

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