Minoxidil Mini-Series: Part 2 – From Blood Pressure to Baldness

In Part 2 of the Avacor® Hair Regrowth Blog “Minoxidil Mini-Series” we will trace the path of minoxidil through the 1970s and 1980s as reports of hair growth led a potent blood pressure (BP) medication to be proposed as a treatment for male pattern baldness (MPB).

Minoxidil was first synthesized in the 1960s by William Anthony and Joseph Ursprung of The Upjohn Company (US Patent No. 3,461,461) and was initially prescribed as a vasodilator for lowering blood pressure in patients with hypertension.1

A few years later, some doctors began to note an unintended effect in patients taking the drug: hair growth.

Early Reports of Hair Growth

Compared to other antihypertensive treatments available at the time, such as propranolol and hydralazine, a 1972 study found that oral minoxidil therapy (later known as Loniten®) provided a significant improvement in blood pressure reduction.2 However, the authors also observed hypertrichosis (excessive hair growth) in five of the eight patients who were treated with the drug for more than two months.

Many subsequent publications during the 1970s confirmed these initial reports of increased hair growth with minoxidil, with observations such as: “side effects included increased hair growth.” 3

This effect may not have been particularly surprising since another vasodilator, diazoxide, had been associated with hypertrichosis in the early 1960s.4 Although chemically unrelated to minoxidil, diazoxide relaxes blood vessels by a similar mechanism (activation of ATP-sensitive potassium channels).

“Reversal of male pattern baldness by minoxidil…”

In the early 1980s, isolated case reports began to emerge that described the “reversal of baldness” by minoxidil.5,6 One patient’s experience was particularly compelling:6

“Within four weeks dark-brown hair (the normal color for this patient) grew over the area of the scalp that had previously been devoid of hair visible to the naked eye and had made up the major portion of his scalp except for the sides and back of his head. By eight weeks these new hairs were approximately 1.3 cm (0.5 in) long. The density of hair and the hair-shaft thickness were equal to those of the areas of this patient's scalp that were normally not subject to balding.”

One prescient report of minoxidil causing “excessive hair growth” on the “temples and forehead,” which was published before the other two reports on baldness, even proposed its use as a topical treatment for androgenetic alopecia:7

“The high incidence of hypertrichosis produced by both diazoxide and minoxidil suggests the possibility that an effective topical formulation might stimulate local hair growth in early male-pattern alopecia…”

The drug’s maker, Upjohn, was already well-prepared to capitalize on the new indication that was being proposed for its drug. By February, 1979, the company had already received a patent covering the use of topical minoxidil compositions for growing hair.

The Upjohn Company Patents Minoxidil for Alopecia

“The invention claimed is: 1. A method of treating humans for alopecia…”

Upjohn was granted two critical U.S. patents covering the use of minoxidil for treating male pattern baldness:

US Patent No. 4,139,619 claimed a “topical composition” that could be used for “increasing the rate of terminal hair growth in mammalian species” and “conversion of vellus hair to growth as terminal hair.”

US Patent No. 4,596,812 claimed a “method of treating humans for alopecia which comprises topically applying to the human scalp an effective amount of a solution containing 6-amino-1,2-dihydro-1-hydroxy-2-imino-4-piperidinopyrimidine and a solvent.”

These patents laid the foundation for the successful commercialization of minoxidil as a treatment for male pattern baldness, under the trade name Rogaine®.

In the next installment of the Avacor Hair Regrowth Blog “Minoxidil Mini-Series,” we will describe the clinical trials that proved minoxidil’s effectiveness against alopecia in men and women, as well as the approval by the FDA of minoxidil as the first treatment for male pattern hair loss. Check back here soon for Part 3 – Efficacy in Clinical Trials.

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1. Gilmore E, Weil J, Chidsey C. Treatment of essential hypertension with a new vasodilator in combination with beta-adrenergic blockade. N Engl J Med. 1970 Mar 5;282(10):521-7. Link to Pubmed

2. Gottlieb TB, Katz FH, Chidsey CA 3rd. Combined therapy with vasodilator drugs and beta-adrenergic blockade in hypertension. A comparative study of minoxidil and hydralazine. Circulation. 1972 Mar;45(3):571-82. Link to Pubmed

3. Jacomb RG, Brunnberg FJ. The use of minoxidil in the treatment of severe essential hypertension: a report on 100 patients. Clin Sci Mol Med Suppl. 1976 Dec;3:579s-581s. Link to Pubmed

4. Okun R, Russell RP, Wilson WR. Use of diazoxide with trichlormethiazide for hypertension. Arch Intern Med. 1963 Dec;112:882-8. Link to Pubmed

5. Seidman M, Westfried M, Maxey R, Rao TK, Friedman EA. Reversal of male pattern baldness by minoxidil. A case report. Cutis. 1981 Nov;28(5):551-3. Link to Pubmed

6. Zappacosta AR. Reversal of baldness in patient receiving minoxidil for hypertension. N Engl J Med. 1980 Dec 18;303(25):1480-1. Link to Pubmed

7. Burton JL, Marshall A. Hypertrichosis due to minoxidil. Br J Dermatol. 1979 Nov;101(5):593-5. Link to Pubmed