ARTICLE
Auteur(s) : Serge Ahouansou1, Philippe Le
Toumelin1, Béatrice Crickx1, Vincent
Descamps2
1Department of Public Heatlh, Avicenne Hospital,
Assistance Publique-Hôpitaux de Paris, 93009 Bobigny Cedex
2Department of Dermatology, Bichat Claude Bernard
Hospital, Assistance Publique-Hôpitaux de Paris, 75018 Paris
accepté le 3 Janvier 2007
An association between androgenetic alopecia and severe coronary
heart disease has been reported in many epidemiological studies
[1-7]. In the Framingham Heart Study development of alopecia during
adulthood was associated with coronary heart disease [3]. But the
mechanism underlying this association remains unclear.Many
explanations have been proposed including insulin resistance,
atherosclerotic processes, higher levels of androgen that may
contribute to both atherosclerosis and thrombosis, adverse effects
of lipid-lowering or antihypertensive drugs.Recently we observed
that overexpression of mineralocorticoid receptors targeted to the
skin induced the development of alopecia in a double transgenic
mouse model (Yannis Sainte-Marie, personal communication, ESDR
2006, manuscript in preparation). Mineralocorticoid receptors have
been found in skin epithelium [10]. But the role of
mineralocorticoids in the skin remained unknown. The role of
mineralocorticoid pathways may be discussed in the development of
androgenetic alopecia. Essential hypertension is now considered to
be associated with primary hyperaldosteronism. It was recently
demonstrated that increased aldosterone levels within the
physiological range predisposed people to the development of
hypertension [9].We evaluated in a prospective practice-based study
the association between androgenetic alopecia and hypertension.
Methods
White men aged 35-65 years were consecutively included in this
study by five physicians (general practitioners). A total
population of 250 Caucasian patients were recruited (50 per
physician). The physicians were informed that the aims of this
study were to evaluate the prevalence of androgenetic alopecia in
this population and to study the association with cardiovascular
risk factors (history of personal hyperlipidemia, blood pressure or
history of hypertension, history of personal diabetes mellitus,
smoking), familial history of androgenetic alopecia and
antihypertensive drugs.
A pre-printed examination form with a scheme of a simplified
version of the Norwood’s classification of androgenetic alopecia in
5 grades (0-4) was used to collect standardized information
[8].
Anonymously collected data included age, 5 grades of
androgenetic alopecia (0-4), hypertension, history of familial
androgenetic alopecia, history of personal diabetes mellitus,
smoking, history of personal hyperlipidemia, antihypertensive drugs
(name). Excluding criteria included history of cancer, some
treatments (corticosteroids, interferon, antimitotic, retinoid,
lithium, finasteride, testosterone, danazol).
Hypertension was defined by a systolic and diastolic blood
pressure over 140 and 90 mmHg, respectively. Patients with normal
blood pressure but treated for hypertension were considered as
hypertensive. Hyperlipidemia was defined by history of abnormal
values (cholesterol or triglycerides).
Three groups of patients were defined 35-45 years, 46-55 years,
and 56-65 years.
Patients’ data were recorded in a computerized database.
Statistical analyses were conducted using SAS v8.2 (SAS Institute
Inc, Cary, NC). The baseline characteristics of the study patients
were expressed as numbers and percentages for categorical variables
(hypertension, hyperlipidemia, history of familial hypertension,
history of familial androgenetic alopecia, diabetes mellitus,
smoking, treatment) and as means ± standard deviations (SD) for
continuous variables. For univariate analysis, the Chi-square and
Fisher exact test were used for categorical variables and a Student
test was used for the comparison of the age according to the
presence or not of alopecia. The variables with the threshold of
0.1 in these univariate analysis were selected, like explanatory
variables of the alopecia in a logistic model of regression step by
step. Only the results with the threshold of 0.05 were regarded as
significant with the logistic model of regression.
Results
250 patients were recruited by 5 general practitioners. 38% of the
patients had hypertension. 65% of the patients had androgenetic
alopecia. The distribution of androgenetic alopecia in the
different stages is described in figure 1. 82% of
hypertensive patients had alopecia. 56% of non hypertensive
patients had alopecia. The association between hypertension and
androgenetic alopecia was highly significant (p < 0.001).
This association was always highly significant when we only
considered the patients belonging to the stages 2-3-4 as compared
to the stages 0-1 (p < 0.001).
One evident bias was the increase of both hypertension and
alopecia with age (figure 2). We analysed the
association of risk factors with alopecia by logistic regression
analysis to calculate the odds ratio and 95% CI for each variable.
Odds ratio was 2.195 (95% CI : 1.1-4.3) for hypertension, 10.870
(95% CI : 4.3-27.1) for familial history of alopecia, 1.05 (95% CI
: 1.0-1.088) for age (when all scores of alopecia were considered).
We confirmed that the association of hypertension and alopecia was
independent of age. No association was demonstrated for other
variables (smoking, diabetes mellitus, hyperlipidemia which
represented 40.8%, 9.2%, 33% of the patients, respectively). No
significant difference was observed between the results of the 5
physicians.
Discussion
Many studies have reported the association of androgenetic alopecia
with severe coronary heart disease without any obvious explanation
[1-7]. Few studies have discussed the role of hypertension. In one
study vertex baldness was more strongly associated with coronary
heart disease risk among men with hypertension (multivariate RR,
1.79; 95% CI, 1.31-2.44) [7]. We demonstrate in this study an
association between hypertension and androgenetic alopecia.
Androgenetic alopecia could be considered as a clinical marker of a
risk for hypertension. It may illustrate the role of the
mineralocorticoid pathway in alopecia. Skin and hair follicles
normally express mineralocorticoid receptor. We previously
demonstrated in our laboratory that skin had all of the enzymes
required for mineralocorticoid pathways (11 beta-hydroxysteroid
dehydrogenase) [10]. Interestingly, spironolactone, an antagonist
of the mineralocorticoid receptor, has been used for a long time to
treat androgenetic alopecia in women. It was considered that
spironolactone worked through its anti androgenic action. We
recently developed an original model of double transgenic mice with
overexpression of the mineralocorticoid receptor targeted to the
skin. In these adult mice, overexpression of the mineralocorticoid
receptor in the skin induced the development of alopecia
(manuscript in preparation). This observation confirms the role of
the mineralocorticoid pathway in hair physiology and suggests that
spironolactone could work directly as a mineralocorticoid receptor
antagonist.
It is clear that association of androgenetic alopecia and
hyperaldosteronism warrants additional studies. On the other hand
hypertension may be a consequence of insulin linked disturbance as
in diabetes. In a recent report, hypertension and the use of
antihypertensive drugs were found more common among Finnish men
with androgenetic alopecia (61% versus 45% and 50% versus 26%,
respectively) [11]. But the rates of diabetes and hyperinsulinemia
were also higher in men with androgenetic alopecia compared to men
with normal hair status (21% versus 12% and 61% versus 49%).
But considering our data, two explanations may be proposed to
explain the association of hypertension and androgenetic alopecia :
(1) androgens which bind to mineralocorticoid receptors might be
responsible for the observed difference in blood pressure and for
instance may participate in the higher susceptibility to
hypertension in men as compared to women [12], (2)
hyperaldosteronism which is considered to be responsible for most
of primary hypertensions may directly participate in the
development of alopecia.
In another recent report devoted to androgenetic alopecia in
women, a relationship between androgenetic alopecia and high blood
pressure (p = 0.02, RR = 1.69) was also demonstrated [13].
These data may suggest the use of mineralocorticoid antagonists
in the treatment of androgenetic alopecia. Spironolactone is a
non-selective mineralocorticoid receptor antagonist with moderate
affinity for androgen receptors and dose-dependent sexual side
effects. New generations of aldosterone receptor antagonists
selective for aldosterone receptors alone could be of interest for
evaluation in the treatment of androgenetic alopecia.
Acknowledgements
We want to thank Dr Denis Malbeck, François Vellieux, Nadir
Hammoumrhaoui, Edouard Mouyabi who participated in this study.
Financial support : none. Conflict of interest : none.
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