Is Early-onset Androgenetic Alopecia Associated with Metabolic Syndrome? – A Descriptive Cross-sectional Study

ABSTRACT

Background:

Androgenetic alopecia (AGA), although considered medically benign, has been found to be associated with increased cardiovascular risk, especially in patients with early onset (≤ 30 years). Metabolic syndrome (MetS) comprises a cluster of cardiovascular risk factors predicting morbidity. Very few studies focused on early development of MetS in younger males and the association with the severity of AGA, necessitating further research.

Objectives:

To estimate the prevalence of MetS in men with early-onset AGA and to assess if there is a positive correlation between the severity of AGA and the development of MetS and its components.

Materials and Methods:

A cross-sectional study was undertaken in a tertiary care hospital from November 2020 to October 2022, on men in the age group of 18 – 40 years. 100 men with early-onset AGA (≤ 30 years) were included in the study. MetS was diagnosed as per the criteria by the International Diabetes Federation (IDF), and American Heart Association/ National Heart, Lung and Blood Institute (AHA/NHLBI). Chi-square test and student’s t-test were used for statistical analysis.

Results:

Metabolic syndrome was diagnosed in 63 (63%) of the patients. The prevalence of MetS (P = 0.006), elevated waist circumference (P = 0.006), elevated serum triglycerides (P = 0.011), and mean value of serum high-density lipoprotein (P = 0.05) was statistically significant in patients with severe AGA.

Conclusion:

A high prevalence of metabolic syndrome was found in young males with early-onset AGA. Screening and lifestyle modifications should be enforced earlier to lessen cardiovascular morbidity and mortality in young male patients with AGA.

INTRODUCTION

Androgenetic alopecia (AGA), or patterned hair loss, is the most common type of alopecia. Male pattern hair loss (MPHL) is because of androgens causing miniaturization of androgen-sensitive hair follicles. The general consensus is that laboratory investigations are not essential in AGA.[1]

The prevalence of early-onset AGA, defined as the onset of MPHL in men ≤30 years, is on the rise. The psychological and cosmetic impact prompts young men to seek medical help. There have been studies that address its association with various risk factors for cardiovascular diseases.[2,3]

Metabolic syndrome (MetS) is a cluster of interrelated cardiometabolic risk factors which increase the risk of atherosclerotic disease and type 2 diabetes mellitus. The areas of concern in the epidemic of cardiovascular diseases in India are early onset affecting the young population and the high fatality rate.[4] Early intervention is the need of the hour in reducing cardiovascular morbidity and mortality.

However, there are very few studies focusing on the early development of MetS in young males (<40 years) with early-onset AGA, the effect of clinical characteristics of AGA on the development of MetS, and data pertaining to the Indian context. Our study estimated the prevalence of MetS in young Indian males with early-onset AGA; we also assessed the development of MetS and its components based on the clinical characteristics of AGA, such as severity, age of onset, duration, and family history, to aid in understanding which patients with AGA need to be subjected to early screening for cardiovascular diseases.

MATERIALS AND METHODS

A hospital-based cross-sectional study was undertaken on 100 patients attending the dermatology outpatient department between November 2020 and October 2022. Male patients aged 18–40 years with early-onset AGA (≤30 years) were included in the study. The study was limited to male patients because the role of androgens in female pattern hair loss is controversial, and other factors have been proposed to play a role in its etiology.[5] Patients with potential confounding factors such as chronic smoking, chronic alcoholism, corticosteroid therapy, hormone replacement therapy, diagnosed thyroid disorders, and dermatological conditions known to be associated with MetS such as psoriasis were excluded from the study. Approval was obtained from the Institutional Ethics Committee (Ref. No. 437/2020). The study was registered with the Clinical Trials Registry – India (CTRI/2022/01/039509). A written informed consent was taken from all the participants.

A predesigned pro forma was used to collect data on patient demographics, age, age of onset of AGA, duration of AGA, family history of AGA, history of known comorbidities, treatment history, and smoking and alcohol consumption. AGA was diagnosed based on history and cutaneous examination and graded based on the modified Norwood–Hamilton grading scale. Patients with AGA Grades – I, II, IIa, III, IIIa, and IIIv – were classified as mild AGA, and patients with AGA Grades – IV, IVa, V, Va, VI, and VII – were classified as severe AGA.

Height was measured using a wall-mounted stadiometer with the patient in barefoot, full erect posture, and with head held straight. Weight was recorded with the subjects wearing light clothes and without footwear. The body mass index (BMI) was calculated using the formula weight (in kg) divided by height (in m²). Waist circumference (WC) was measured using a nonextendable measuring tape, at the midpoint between the lower margin of the 12^th rib and the upper margin of the iliac crest. Blood pressure (BP) was measured using a sphygmomanometer in the sitting position on the right arm after a 20-min rest. It was measured twice, and an average of the two values was taken. Blood samples were drawn by venepuncture after a 12-h fast. Fasting blood sugar (FBS), serum triglycerides (TG), and serum high-density lipoprotein cholesterol (HDL-C) were measured.

MetS was diagnosed based on the joint interim statement issued by the International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute.[6] The presence of any three of the following was considered diagnostic.

1. Elevated WC ≥90 cm in males (ethnicity-specific definition)

2. Elevated triglycerides ≥150 mg/dL or drug treatment for elevated triglycerides

3. Reduced HDL-C <40 mg/dL in males or drug treatment for reduced HDL-C

4. Elevated BP: Systolic BP (SBP) ≥130 mmHg and/or diastolic BP (DBP) ≥85 mmHg

5. Elevated FBS ≥100 mg/dL or drug treatment of elevated glucose.

Statistical analysis

Data were analyzed using the Statistical Package for the Social Sciences (SPSS) version 24.00 (SPSS Inc. 233, South Walker Drive, 11th Floor, Chicago, IL). All categorical data were summarized using frequency and percentages; all continuous data were described using mean and standard deviation or median and interquartile range based on the distribution. The sample size was calculated based on the prevalence reported in previous studies.[7] To estimate the prevalence of MetS with an absolute precision of 10% and 95% confidence interval, the required minimum sample size was 96 patients, which was rounded off to 100.

Clinical parameters were compared using the Chi-square or Fisher’s exact test for categorical observations and independent t-test or Mann–Whitney U-test for continuous observation, based on their distribution. P value was considered significant at a 5% level of significance for all comparisons.

RESULTS

The study included 100 male patients with early-onset AGA. Most of the patients were in the age group of 18–25 (40%) years. Patient characteristics are given in Table 1. The age of onset in our study ranged from 14 to 30 years with a mean of 22.9 ± 4.34 years. The duration of AGA ranged from 0.5 to 18 years, with a median of 4 years, and most participants had AGA between 1 and 5 (47%) years. The most common grade of AGA was Grade III vertex (38%). Seventy (70%) were classified as mild AGA, and 30 (30%) were classified as severe AGA.

Table 1.

Demographic and laboratory parameters of patients

Parameters	Measurement, mean±SD	Prevalence of derangement in AGA, n (%)
Age (years)	27.26±4.87	NA
Age of onset (years)	22.9±4.34	NA
Duration (years), median (IQR)	4 (4)	NA
Family history of AGA, n (%)	72 (72)	NA
Height (cm)	170.2±4.46	NA
Weight (kg)	72.84±11.58	NA
BMI (kg/m2)	25.18±3.95	71 (71)
WC (cm)	91.92±4.56	75 (75)
SBP (mmHg)	131.3±11.6	64 (64)
DBP (mmHg)	87.07±8.53	64 (64)
FBS (mg/dL)	91.9±19.84	30 (30)
TG (mg/dL)	141±61.2	41 (41)
HDL-C (mg/dL)	38.55±8.90	65 (65)

SD – Standard deviation; IQR – Interquartile range; BMI – Body mass index; TG – Serum triglycerides; HDL-C – High density lipoprotein cholesterol; AGA – Androgenetic alopecia; NA – Not available; DBP – Diastolic blood pressure; SBP – Systolic blood pressure; FBS – Fasting blood sugar; WC – Waist circumference

The prevalence of MetS was found to be 63% (n = 63). MetS was diagnosed in 25 patients with severe AGA (83%) and 38 patients with mild AGA (54%) with a statistically significant difference (P = 0.006). Prevalence of central obesity (P = 0.006) and elevated serum triglycerides (P = 0.011) were also significantly higher in patients with severe AGA [Table 2]. There were statistically significant differences in mean values of WC (P = 0.006), HDL-C (P = 0.05), and TG (P = 0.021) between patients with severe and mild AGA [Table 3].

Table 2.

Association between severity of androgenetic alopecia and development of metabolic syndrome, derangement of components, and increased body mass index

	Mild AGA, n (%)	Severe AGA, n (%)	P
Metabolic syndrome	38 (54)	25 (83)	0.006
Central obesity	47 (67)	28 (93)	0.006
Elevated BP	50 (71)	26 (87)	0.102
Elevated SBP	42 (60)	22 (73)	0.203
Elevated DBP	43 (61)	21 (70)	0.413
Elevated FBS	6 (9)	4 (13)	0.467
Elevated TG	23 (33)	18 (60)	0.011
Reduced HDL-C	44 (63)	21 (70)	0.493
Increased BMI	49 (70)	22 (73)	0.736

BP – Blood pressure; FBS – Fasting blood sugar; TG – Serum triglycerides; HDL-C – High density lipoprotein cholesterol; BMI – Body mass index; AGA – Androgenetic alopecia; SBP – Systolic BP; DBP – Diastolic BP

Table 3.

Mean of the components of metabolic syndrome in mild androgenetic alopecia and severe androgenetic alopecia

	Mild AGA, mean±SD	Severe AGA, mean±SD	P
WC (cm)	91.1±4.73	93.8±3.56	0.006
SBP (mmHg)	130.6±11.79	132.8±11.18	0.39
DBP (mmHg)	86.7±8.91	88±7.63	0.494
FBS (mg/dL)	91.4±16.8	93±25.91	0.711
TG (mg/dL)	131.8±56.44	162.5±67.15	0.021
HDL-C (mg/dL)	39.7±9.7	35.9±6.04	0.05

BP – Blood pressure; FBS – Fasting blood sugar; TG – Serum triglycerides; HDL-C – High density lipoprotein cholesterol; SD – Standard deviation; WC – Waist circumference; SBP – Systolic BP; DBP – Diastolic BP; AGA – Androgenetic alopecia

A higher prevalence of MetS was noted in patients with a duration of AGA ≥5 years, but the difference was not statistically significant (P = 0.145). Hypertension was significantly associated with increased duration of alopecia (P = 0.036) [Table 4].

Table 4.

Association between duration of androgenetic alopecia and development of metabolic syndrome, derangement of components, and increased body mass index

	Duration <5 years, n (%)	Duration ≥5 years, n (%)	P
Metabolic syndrome	35 (57)	28 (72)	0.145
Central obesity	42 (69)	33 (85)	0.076
Elevated BP	42 (69)	34 (87)	0.036
Elevated SBP	33 (54)	31 (80)	0.01
Elevated DBP	36 (59)	28 (72)	0.194
Elevated FBS	6 (10)	4 (10)	0.946
Elevated TG	22 (36)	19 (49)	0.21
Reduced HDL-C	39 (64)	26 (67)	0.78
Increased BMI	42 (69)	29 (74)	0.554

BP – Blood pressure; FBS – Fasting blood sugar; TG – Serum triglycerides; HDL-C – High density lipoprotein cholesterol; BMI – Body mass index; SBP – Systolic BP; DBP – Diastolic BP

The prevalence of MetS was lesser in patients who had a family history of AGA, but the difference was not statistically significant (P = 0.53).

The difference in the prevalence of MetS based on the age of onset of AGA was minor and also not statistically significant (P = 0.822). Increased BMI (≥30 kg/m²) was found in the majority of the patients (71%). Increased BMI was not associated with severity, duration, or family history of AGA.

DISCUSSION

In the background of increasing evidence of the association between AGA and cardiovascular risk factors such as MetS, insulin resistance, and carotid atheromatosis, our study aimed to assess the prevalence of MetS in young Indian males and the clinical characteristics of AGA associated with MetS and its components. The research could aid in establishing screening guidelines and thereby significantly reduce cardiovascular morbidity in the young.

Literature states that younger patients are more likely to seek medical help for AGA.[8] Concordant to this, most of the patients in our study were in the age group of 18–25 (40%) years. We found that patients were more likely to seek treatment in the initial years and when they had mild-to-moderate AGA. This could be because premature signs of AGA cause a significant impact on quality of life as reported by Sehgal et al.[9] After the initial years of the disease, as the severity increases, patients stop seeking treatment. A family history of AGA is a risk factor for the development of early-onset AGA as reported by Ding et al.[8] A family history of AGA was present in 72% of the patients.

Our study showed a 63% prevalence of MetS in young males with early-onset AGA which was comparatively higher than the prevalence of MetS estimated in a meta-analysis by Krishnamoorthy et al.[10] The exact mechanisms of the association between MetS and the various skin diseases remain vague. However, emerging evidence suggests that increased insulin resistance, impaired insulin signaling, as well as chronic inflammation are major risk factors that may induce skin diseases.[11,12] Of the above, chronic inflammation tends to correlate more with AGA. Similar results were seen in the studies by Arias-Santiago et al.,[3] but a lesser prevalence was reported in the studies by Gopinath and Upadya[13] and Sheikh et al.[14] The difference in prevalence could be attributed to the age of the patients, sample size, and criteria used for diagnosis of MetS in the various studies. The lower cutoff values in the criteria used in our study[6] could probably explain the higher prevalence of MetS in our study.

In our study, patients with severe AGA had a statistically significant higher prevalence of MetS which was similar to the results obtained by Dharam Kumar et al.[7] and Sheikh et al.[14] However, Gopinath and Upadya[13] concluded that there was no association. This probably could be due to the differences in the classification of the patients into various severity groups. Elevated WC was found in 75% of our patients, and it was significantly associated with the severity of AGA. In the study by Gopinath and Upadya, central obesity was significantly associated with the grade of alopecia (P = 0.04).[13] Arias-Santiago et al. proposed that patients with AGA undergo an abdominal redistribution of fat.[3] Increased abdominal fat tissue is known to be associated with other metabolic disorders such as hypertension, insulin resistance, and dyslipidemia. Increased WC is associated with a risk for coronary artery disease.[15]

Among our patients, 76% had elevated BP. This was not associated with the severity of AGA even though the prevalence of elevated BP was higher in the group with severe AGA. The association between AGA and hypertension can be explained by two mechanisms. The androgens implicated in AGA bind with mineralocorticoid receptors, which favor an increase in BP. Furthermore, hyperaldosteronism which underlies the development of hypertension directly influences the development of alopecia.[16] Arias-Santiago et al. found similar testosterone values in patients with AGA and controls and concluded that elevated BP could be explained by an increase in the peripheral sensitivity to androgens. They also found high aldosterone levels in their cases.[3] Gopinath and Upadya reported elevated BP in 49.4% of patients with AGA, and it was the component found in high frequency in their study (P = 0.029); however, they did not find a significant association with the severity of AGA.[13]

An elevated FBS level was noted in 30% of our patients. In our study, elevated FBS was not associated with the severity of AGA, and these results were comparable to that of Gopinath and Upadya,[13] Dharam Kumar et al.,[7] and Matilainen et al. found an association between early AGA and the development of insulin resistance.[2] It has been postulated that an excess of insulin as a result of peripheral resistance could produce a vasoconstriction and nutritional deficit in the hair follicles, thereby favoring the effect of dihydrotestosterone on follicular miniaturization.[17]

Forty-one percent of the patients in our study had elevated levels of serum triglycerides. The prevalence of elevated serum triglycerides in severe AGA was statistically significant. Dharam Kumar et al. also reported a significantly higher mean value of serum triglycerides in patients with severe AGA.[7] Sixty-five percent of our patients had decreased serum HDL. The prevalence of reduced HDL, however, was not significantly higher in severe AGA in our study. Gopinath and Upadya also had similar results (P = 0.08).[13] The value of HDL in severe AGA (35.9 ± 6.04 mg/dL) was found to be significantly lower than in mild AGA (39.7 ± 9.7 mg/dL). Sadighha and Zahed found significantly high triglycerides and low HDL-C in patients with AGA (P < 0.01).[18] In contrast, Guzzo et al. found no significant difference in the lipid profile.[19] Dyslipidemia in patients with AGA contributes to the development of cardiovascular disease. Sharrett et al. reported that both high triglycerides and low HDL-C were associated with the transition of atheroma to atherothrombosis and stressed the control of both these cardiovascular risk factors even in patients with subclinical disease.[20]

We found that there was no significant association between the duration of AGA and the prevalence of MetS, though the prevalence was higher in patients with a duration of AGA ≥5 years. The prevalence of derangement of all components of MetS was higher in patients with an increased duration of AGA except FBS. However, only elevated BP and SBP were significantly associated with increased duration of AGA. In the study by Gopinath and Upadya, MetS, hypertension, and elevated plasma glucose were significantly associated with increased duration of AGA.[13]

We found no significant association between the age of onset of AGA and the prevalence of MetS and between family history of AGA and MetS. The prevalence of elevated DBP, FBS, triglycerides, and HDL was also lower in patients with family history of AGA. However, the difference was statistically significant between the two groups only pertaining to HDL (P = 0.007).

The prevalence of raised BMI (overweight, preobese, and obese) was higher in those with greater severity of AGA and longer duration of AGA but was not statistically significant. Patients with a family history of AGA were found to have a lower prevalence of increased BMI.

Limitations

The study did not include a control group, and so, the association between AGA and MetS in our study population could not be analyzed. Being a cross-sectional study, the temporal relationship between AGA and MetS could not be assessed.

Further studies with larger sample sizes are required to confirm the association between the severity, grade, duration, age of onset, and family history of AGA with MetS and its components.

CONCLUSION

In the present study, we found a high prevalence of MetS in young men with early-onset AGA. MetS was significantly associated with severe AGA. Young males with early-onset AGA, especially if they have AGA of Grade IV or above, would benefit from early screening for MetS to lessen cardiovascular morbidity and mortality. Patients need to be counseled regarding the risk and advised of lifestyle modifications to prevent untoward complications. It is suggested that severe early-onset AGA be considered an indicator of MetS.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

IADVL PG thesis grant 2020.