Androgenetic alopecia and coronary artery disease in women
Published Web Location
https://doi.org/10.5070/D38525g87bMain Content
Androgenetic alopecia and coronary artery disease in women
Parvin Mansouri MD1, Mohammadreza Mortazavi MD2, Masood Eslami MD3, Mona Mazinani MD4
Dermatology Online Journal 11 (3): 2
1. Department of Dermatology,Imam Khomeini Hospital, Tehran University of Medical Sciences , Tehran, Iran. mortazavir@yahoo.com
2. Dermatologist, Department of surgery ,Wound Healing Research Group, University of Alberta, Edmonton, Alberta, Canada 3.
Department of Cardiology, Imam Khomeini Hospital, Tehran University of Medical sciences 4. Imam Khomeini Hospital, Tehran
University of Medical Sciences, Tehran
Abstract
The meaningful association of androgenetic alopecia (AGA) and coronary artery disease (CAD) in men has been documented, but few studies, if any, have focused on this association in women. This study was carried out on 106 women under the age 55, who completed angiography procedures for diagnosis of coronary artery disease. The aim of study was to assess the relationship between androgenetic alopecia and coronary heart disease in women. The clinical and paraclinical information was obtained by personal interview, physical examination, and review of patients' files. Androgenetic alopecia in the patients was assessed blindly by a dermatologist, using Ludwig's baldness grading system (I to III). According to the angiographic studies, 51 cases had CAD and 55 subjects did not. On the other hand, 21 patients had female AGA (Grade I, 15; Grade II, 3; Grade III, 3 cases). The correlation of AGA and CAD, AGA and previous history of myocardial infarction, and graying of hair and CAD were statistically significant (p < 0.05), after adjustment of data for differences in age. These data support the hypothesis that female AGA, like male pattern baldness, is associated with CAD in women under the age 55.
Introduction
Several published studies have revealed an association between androgenetic alopecia (AGA) and coronary artery disease (CAD) in men [1-10]. Lotufo et al. in one of the largest studies on 19,112 male physicians during an 11-year period showed an association between severity of baldness and coronary artery disease [1]. Another study conducted by Ford et al. uncovered a correlation between severe baldness and coronary disease mortality [2]. Lesko et al. in a case-control study suggested that baldness on the vertex of the scalp was associated with myocardial infarction in men [3]. Although the Framingham Heart Study did not find baldness to be associated with an increased risk of heart disease, men under age 55 who had very rapid onset and progressive androgenetic alopecia were found to be slightly more prone to develop coronary heart disease [4].
Few studies examined CAD risk factors in relation to androgenetic alopecia in men [5, 6]. One study revealed that fronto-occipital male pattern baldness in young men was associated with an increased serum cholesterol level and higher blood pressure compared to men of similar age with no hair loss [5].
To the best of our knowledge, there are few, if any, reports about association of androgenetic alopecia and coronary artery disease in women. In the present study, we have investigated the presence or absence of this correlation.
Methods
Recruitment and data collection
To perform a descriptive, analytic, cross-sectional study, a total of 106 women under age 55 years were recruited from the heart-catheterisation wards of Tehran Medical University and Shahid Rajaee heart hospitals during 1 month. The sampling was done by enumeration considering the factors of sex (female), age (under age 55) and presence of angiography report.
Coronary angiography, the gold standard for diagnosis of CAD,was obtained on these patients because they had severe angina pectoris or unstable angina (50 %), significant ventricular fibrillation with or without myocardial infarction (20 %), marked defect in thalium scan (20 %), and clearly pathological exercise test (10 %).
According to the angiography results, the patients were divided into two groups, those with CAD and those without CAD. The clinical and paraclinical data were collected by interview, observation, physical examination, and review of the patients' files; these were recorded in special questionnaires and tables. Family history of CAD, myocardial infarction (MI) and AGA and personal history of CAD, myocardial infarction, cigarette smoking, and amenorrhea were recorded at the time of recruitment. The coronary risk profiles including blood pressure, pulse rate, and serum cholesterol were measured by trained personnel. The average of the second and third lying and standing systolic and diastolic blood pressures were recorded. The diagnosis of female androgenetic alopecia was made by a dermatologist who was blinded to the angiographic results, after clinical examination of the patients and using Ludwig's baldness grading system (Grade I to III).
Statistical analysis
All statistical analyses were carried out using "Epi-Info" statistical software program (version 6). Chi-square test was used for bivariate associations and multiple comparisons. P value < 0.05 was accepted as evidence of statistical significance.
Results
Of the 106 women aged under 55 years who tolerated cardiac angiography, 51 patients had CAD and 55 subjects did not. The average age was 45 years. Androgenetic alopecia was present in 15 (29 %) of 51 patients with CAD and in 6 (11 %) of 51 patients without CAD.
The frequency of the other variables, baldness pattern, and CAD risk factors are summarized in Table 1.
| Item | Frequency(n) | % |
|---|---|---|
| Female androgenetic alopecia | 21 | 20 |
| Grade I | 15 | 71 |
| (Ludwig grading) Grade II | 3 | 14 |
| Grade III | 3 | 14 |
| Coronary artery disease | 51 | 48 |
| Family history of heart disease | 41 | 39 |
| Family history of androgenetic alopecia | 31 | 29 |
| Previous history of myocardial infarction | 25 | 24 |
| Smoking | 6 | 6 |
| Amenorrhea | 25 | 24 |
| Infertility | 4 | 4 |
| Hirsutism | 16 | 15 |
| Gray hair | 76 | 72 |
| Facial wrinkle | 75 | 71 |
| Acne vulgaris | 14 | 13 |
| High blood pressure (>140/90 mmHg) | 43 | 41 |
| High serum cholesterol (>240 mg/dl) | 48 | 46 |
| Anemia | 58 | 55 |
| Thyroid disease | 21 | 20 |
There were statistically significant correlations between female androgenetic alopecia (AGA) and coronary artery disease (p = 0.0l, Relative Risk (RR) = 1.26) (Fig. 1); between AGA and previous history of myocardial infarction (p = 0.02, RR = 1.42) (Fig. 2) ; and between graying of the hair and CAD (p = 0.0000) Fig. 3) (Tables 2 and 3).
|
|
Coronary Artery disease |
Family history of AGA |
History of previous acute MI |
High blood pressure |
| Female androgenetic alopecia |
p = 0.01 RR=1.26 |
p = 0.009 RR= 1.61 |
p = 0.02 RR=1.42 |
p = 0.02 RR=1.62 |
|
|
Female Androgenetic alopecia |
Graying of hair |
History of previous acute MI |
High blood pressure |
| Coronary artery disease |
p = 0.01 RR=1.26 |
p = 0.0000 RR= 8.35 |
p = 0.0002 RR= 1.5 |
p = 0.0027 RR=1.65 |
|
|
| Figure 1 | Figure 2 |
|---|
|
| Figure 3 |
|---|
The levels of serum blood sugar and triglyceride were within normal limits in nearly all of the patients in this study and none of the patients had diabetes mellitus.
The relationship between AGA and high blood pressure (p = 0.02, RR = 1.69), CAD and hypertension (p = 0.0027, RR = 1.65), AGA and family history of AGA (p = 0.009), CAD and history of myocardial infarction (p = 0.0002), CAD and facial wrinkles (p = 0.011), all were statistically significant (Tables 2 and 3). However, as some of these variables may show association with age per se, they were adjusted for differences in age. In the correlation of graying of the hair with CAD, and that of high blood pressure with CAD, age was not a confounding factor; in the relationship of CAD with facial wrinkles it was a confounder.
On the other hand, there was not statistically meaningful relationship between CAD and AGA severity, AGA and aging, AGA and anemia, AGA and thyroid disease.
The relationship of both CAD and AGA with smoking, high cholesterol levels, hirsutism, acne and amenorrhea were not statistically significant.
Discussion
That male pattern baldness may be a risk factor for cardiovascular disease was first suggested by Cotton et al. [7] in 1972 when they showed an association between the occurrence of coronary artery disease (CAD) and baldness. Several subsequent studies, almost all conducted in male patients, appeared to support the early findings.
Hambley et al. [8] reported that a significantly higher proportion of bald men had CAD than nonbald men. In the studies of Halim et al. [9] and Cooke et al. [10] association of myocardial infarction and CAD with male pattern alopecia was not confirmed.
The Kockum study of risk factors for coronary heart disease [6] reported baldness as a possible important risk factor.
Trevisan et al. [5] in their study on CAD risk factors concluded that patients with fronto-occipital baldness had on the average higher serum cholesterol and blood pressure compared to participants of similar age with no baldness.
The association of the severity of vertex baldness with increased risk of myocardial infarction was reported by Lesko et al. [3] (p < 0.01), which was independent of age. For severe vertex baldness the relative risk was 3.4 (95 % confidence interval, 1.7 to 7.0). In contrast , Herrera et al. [4] showed that the extent of baldness was not correlated with CAD , but the amount of and progression of baldness was associated with CAD occurrence (relative risk (RR)= 2.4, 95 % confidence interval (CI) 1.3-4.4) , CAD mortality (RR = 3.8, 95 % CI 1.9-7.7), and all-cause mortality (RR = 2.4 . 95 % CI 1.5 - 3.8 ). They suggested that rapid male pattern alopecia may be a marker for coronary heart disease.
Although the study of Ford et al. [2] found baldness to be not associated with an increased total rate of CAD incidence or mortality, in men younger than age 55 severe baldness was positively associated with CAD mortality (RR = 2.51 , 95 % CI 1.01 - 6.24) and somewhat less associated with CAD incidence (RR = 1.72 , 95 % CI 0.96 - 3.08). No dose-response relationship with degree of baldness was seen.
Schnohr et al. [11] investigated the correlation between life span and aging signs (such as graying of the hair, baldness, and facial wrinkles) in 20,000 men and women followed for 16 years. No correlation between the mortality and the extent of graying of the hair, baldness, or facial wrinkles in either of the sexes (irrespective of age) was found.
Vertex baldness [1], as previously reported by Lesko et al. [3], was strongly associated with CAD risk among men with hypertension (RR = 1.79, 95 % CI 1.31 - 2.44) or high cholesterol levels (RR = 2.78, 95 % CI 1.09 - 7.12).
Rebora in his thorough review [11] concluded that because 10 of 15 studies performed on the correlation of male pattern baldness and CAD in men reported a statistically significant relationship; this issue cannot be discarded. He also focused on the results of Lotufo's study [1] about a group of subjects who developed baldness before age 30 and the result of another study [13] that showed these subjects to have an unusually elevated serum dihydrotestosterone-testosterone ratio compared with men with later-onset AGA.
The etiology and pathogenesis of AGA are not fully understood yet. Hamilton referred to mutual interplay of genetic factors, androgens, and age factors in the origin of AGA [14, 15]. Polygenic heredity is assumed to be the primary cause of AA, although testosterone plays an important role, seemingly independent of genetic predisposition. Conversion of testosterone into dihydrotestosterone (DHT) in the hair follicles, catalyzed by the enzyme 5-α reductase, and binding of DHT to androgenic receptors in the hair follicle triggers cellular processes that reduce the anagen phase of the hair cycle. For this reason the hair passes earlier into the telogen phase and falls out [16].
The underlying cause of female AGA seems to be the same as for male AGA. Although women with androgenetic alopecia usually do not have higher levels of circulating androgens, they have been found to have higher levels of 5-α reductase, more androgen receptors, and lower levels of cytochrome P450 (which converts testosterone to estrogen) [17].
The incidence of coronary artery disease (CAD) is equal in men and women, with the onset in women typically delayed by about 10 years. Premenopausal women are generally protected from manifestations of ischemic heart disease because of the protective effects of estrogen, but the presence of diabetes mellitus eliminates the protection associated with female sex [18].
The etiology of coronary heart disease is related to multiple risk factors. The most common risk factors are family history of premature CAD, hyperlipidemia including hypercholesterolemia, obesity, hypertension, cigarette smoking, diabetes mellitus, type-A personality, and emotional stress [18]. Although, for a long time, male gender has been suggested as a risk factor of CAD, the presence or absence of a hormonal (androgenic) relationship in both men and women is not well investigated and there is not convincing evidence in favor of such a relationship in the medical literature.
Conclusion
Our study is one of the few investigations about the association of AGA and CAD in women. Regarding the statistically significant correlation between female AGA and CAD, and between AGA and previous history of myocardial infarction, we suggest female androgenetic alopecia as a possible marker for increased risk of CAD events but many questions remain to be answered. Does AGA reflect CAD morbidity and mortality whether associated solely with CAD or metabolic syndrome or obesity? Can AGA be an important predictor of cerebrovascular accident? Is AGA associated with single vessel or multi-vessel CAD? Do patient with AGA respond less well than non-AGA counterparts with similar metabolic profile post-MI?
The relationship between AGA and CAD in men after more than 30 years of investigation is still a controversial issue; larger studies in both men and women are needed to confirm our findings and to answer these questions.
Acknowledgment: The authors would like to thank Dr. Saeed Hashemipour, MD, for his help in gathering the data and coordination between the authors, and Dr. Alireza Makki, Ophthalmologist in Razi Ohthalmology Clinic of Tehran for his help in the funduscopic examination of the patients and taking pictures.
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