Spironolactone is an aldosterone antagonist, potassium-sparing diuretic
used to clinically treat high blood pressure. Potassium-sparing diuretic
acts on the kidneys to increase the flow of urine, resulting therefore to
decreased amount of water in the body. The reduction of water in the body
in turn helps reduce the blood pressure. Unlike some other diuretics, however,
potassium-sparing diuretic medicines do not cause the body to lose an important
electrolyte required by the body—potassium.
To individuals with no hyperandrogenism (an excessive production of male
hormones), spironolactone therapy may reduce hair loss and it may even promote
some hair growth. Moreover, in women with hirsutism, the drug decreases
the growth rate and mean diameter of facial hair.
Spironolactone is a steroid that has a basic four ring steroid nucleus
and is 98 percent protein bound. Its primary metabolite canrenone is at
least 90 percent protein bound. Canrenone is the primary metabolite contributing
to the diuretic effect of spironolactone, and it is also the active antagonist
of the hormone aldosterone.
Spironolactone Absorption and Metabolism in the Body
Spironolactone is rapidly absorbed and its absorption increases with food
intake; maximum plasma levels being reached in 30 to 60 minutes after ingestion.
Depending on the tablet manufacturer, the percentage of the drug that is
detected in the systemic circulation after oral administration exceeds 90
The liver rapidly metabolizes spironolactone. The hydrolytic product of
canrenone is coronate; canrenone is inter-converted into this product enzymatically.
The major metabolites canrenone and potassium canrenoate are excreted through
the urine and bile, and there is no un-metabolized drug that is passed out
via the urine.
Spironolactone Mechanism of Treatment
As define by Dorfman, the term anti-androgen implies prevention of the
action of androgen activity at target sites. It does not include other mechanisms
of decreasing androgen action such as decreasing the production of androgens,
interference with androgen metabolism, or change in androgen plasma protein
binding. An example of potent anti-androgen is spironolactone.
The action of spironolactone, however, is directed at both decreasing production
and blocking the effect of androgens at the cellular level. Spironolactone
decreases the testosterone production in the adrenal gland by depleting
the microsomal cytochrome P450-dependent enzymes 17a-hydroxylase and desmolase.
However, the destruction of spironolactone to the microsomal cytocrome P450
may be limited to those tissues in which microsomal 17-hydroxylase activity
is high. After spironolactone binds to the 17-hydroxylase-cytochrome P450,
it may convert it to spironolactone metabolite that destroys the heme portion
(molecule containing iron) of cytochrome P450 resulting to the decrease
in steroid 17-hydroxylation.
Spironolactone is a competitive inhibitor of DHT-receptor binding and it
also interferes with the translocation of this complex into the nucleus.
A strong competitor for the androgen receptor, spironolactone is a potent
agonist, while canrenone on the other hand is a weak competitor thus a potent
antagonist. The weak agonists are the true antagonists of endogenous and
exogenous androgens; weak antagonists rely mainly on a continuous supply
of the compound to achieve full inhibition. The possible production of the
parent compound in the adrenal gland and the metabolite on the receptor
site produces the anti-androgen effect of spironolactone.
Although it varies, the protestation activity of spironolactone influences
the ratio of luteinizing hormone (LH) to follicle-stimulating hormone (FSH)
by decreasing the response of LH to gonadotropin-releasing hormone (GnRH),
thereby decreasing also the androgen production.
Dosage in Treatment
Spironolactone preparation is available only in 25-mg and 50-mg table.
In clinical practice, spironolactone is given in dosage that varies from
50 to 300 mg per day. It can be given as a single dose or in divided doses.
Similar to that found in hirsutism, the minimum threshold for effective
treatment of pattern hair loss has also been found to be 100 mg daily. Minimal
changes in circulating androgens are observed at doses of 100 mg per day;
however, higher doses of 300 mg or more per day decreases the plasma testosterone
level significantly. Moreover, this increase dosage has almost no clinical
advantage at all; it only serves to increase the side effects.
Studies on the Use of Spironolactone on Hair Loss Treament
Documented reports in the literature regarding the use of spironolactone
in the treatment of pattern hair loss are rare. Some small clinical trials
have shown clinical effect in pattern baldness, however, spironolactone
rarely offers the benefit of hair re-growth.
Studies performed so far includes women only.
- A 12 months study in 12 women with androgen-dependent alopecia was
conducted; with 6 subjects on spironolactone therapy of 75 to 100 mg per
day and with
the other 6 on controls, resulted in both groups to decrease in target
area non-vellus hairs. However, the decrease in the control group was
significant. Two subjects who had their spironolactone dose doubled
after 12 months from the 75 to 100 mg per day used during the first year
enhanced non-vellus growth.
- Six out seven female with pattern baldness treated daily with 200 mg spironolactone showed an improvement
in a second study.
Spironolactone Side Effects
Hyperkalemia, an acute intoxication from potassium, is one of the potential
side effects of spironolactone on both men and women. Worse effect of spironolactone
on men, however, is gynocomastia – excessive development of the male
breast, thus confining the systemic use to women. Other side effects on
men are decreased libido and impotence. In women, the common side effects
are breast tenderness, irregular menses, and mood swings. The use of concomitant
oral contraceptive pill in women of childbearing age is advised because
feminization of male fetus is a possible risk if pregnancy occurs while
they are on spironolactone.