Abstract
Background:
Many studies have associated male androgenetic alopecia with the risk of cardiovascular disorders but very few studies have addressed this association in women with FPHL.
Materials and Methods:
This was a cross-sectional hospital-based study in which a total of 50 women (18-45 years) were recruited. The objective was to measure carotid intima-media thickness (CIMT) by doppler ultrasound, Body mass index (BMI), waist circumference, lipid profile, fasting blood sugar (FBS), insulin, testosterone, Sex hormone binding globulin (SHBG), hs-CRP, ESR and fibrinogen, in pre-menopausal women having FPHL and to correlate these parameters with severity of FPHL. The prevalence of Metabolic syndrome (MetS) and Insulin resistance were evaluated.
Results:
Metabolic syndrome and insulin resistance were found in 12 (24%) and 17 (34%) cases respectively. Hypercholesterolemia, elevated LDL levels and hypertriglyceridemia, low HDL levels and hyperinsulinemia were found in 11 (22%), 31 (62%), 9 (18%), 17 (34%) and 7 (14%) cases respectively. 8 (16%) cases were diabetics. Elevated ESR, increased fibrinogen levels and elevated hs-CRP were found in 43 (86%), 10 (20%) and 21 (42%) cases respectively. CIMT was found to be within its normal range. Correlation of CIMT, anthropometric indices (BMI and WC), biochemical markers (serum cholesterol, triglycerides, FBS, and fibrinogen), and presence of metabolic syndrome with severity of FPHL in terms of Ludwig grade was found to be statistically significant.
Conclusions:
The determination of metabolic syndrome, insulin resistance and acute phase reactants such as hs-CRP and fibrinogen may be useful screening methods to detect increased cardiovascular risk in women with FPHL.
KEY WORDS: Cardiovascular risk factors, female pattern hair loss, metabolic syndrome
Introduction
FPHL is a non-scarring progressive hair loss which results from follicular miniaturization. It is characterized by a progressive decrease in the ratio of terminal hair to shorter, thinner vellus hair in a patterned distribution. There is progressive decline in the duration of anagen and an increase in the duration of telogen.[1] There is reduction in hair density over the crown and frontal scalp with retention of the frontal hair line.
Its prevalence increases with increasing age from around 12% in women in the age group of 20-29 years to over 50% in women above the age of 80 years.[2]
The role of androgen in FPHL is less certain than that in men. Genetic predisposition has been seen and a polygenic mode of inheritance for FPHL has been observed. It has been observed that these genes may determine the severity, pattern, progression and age of onset. Apart from genetics, other factors like hypertension, diabetes mellitus, stress, smoking, obesity, minimal physical activity, hypothyroidism, testosterone and lower serum ferritin levels are considered as risk factors for FPHL.[2] It has been postulated that FPHL is linked to CVD by mechanisms such as hyperinsulinemia, chronic inflammation and peripheral sensitivity to androgens. Association has been seen in early onset FPHL with insulin resistance, hypertension and increased CVD in a large number of studies.[3,4,5,6,7] Determination of metabolic syndrome and ultrasound study of the carotid arteries is recommended to detect the cardiovascular risk factors in patients with FPHL.[1]
There are few studies[3,4,5,6,7] which explored the association between FPHL and presence of cardiovascular risk factors [increased carotid intima-media thickness (CIMT), body mass index, waist circumference dyslipidemia, hyperglycemia, hyperinsulinemia, hyperandrogenemia, increased hs-CRP, ESR, fibrinogen and decreased sex hormone binding globulin (SHBG)] from the Indian subcontinent. The presence of modifiable cardiovascular risk factors in FPHL can help in prevention of CVD.
Materials and Methods
Study design and subjects
This was a cross-sectional hospital-based study in which 50 pre-menopausal women in the age group of 18-45 years with a clinical/trichoscopic diagnosis of FPHL, attending the hair clinic of dermatology outpatient department of Smt Sucheta Kriplani hospital were enrolled in the study after taking consent for the same by institutional ethics committee and giving information leaflet.
All the cases were evaluated in detail and their demographic details, history, clinical examination and investigations were sent and recorded as per the clinical proforma. Inclusion criterias were: all pre-menopausal women of 18-45 years of age fulfilling the clinical/trichoscopic diagnostic criteria of Ludwig grade 1-3. Exclusion criterias were: menopausal women, women with bilateral oophorectomy; telogen effluvium, alopecia areata, cicatricial alopecia; women on hormone replacement therapy/contraceptive pills/corticosteroid therapy or known case of PCOD/those fulfilling PCOD clinical criteria; known case of diabetes mellitus, hypertension, autoimmune diseases, thyroid disorders, malignancies or chronic inflammatory skin diseases, alcoholics [females having ≥1 drink (20 g) per day] and smokers.
All subjects underwent anthropometric assessment like measurement of height, weight, BMI and waist circumference. Systolic and diastolic blood pressure was measured using sphygmomanometer on the right arm in sitting position and interpreted according to ACC/AHA criteria for hypertension 2017. Ten ml blood was collected from antecubital vein after overnight fasting (12 hours). Thyroid stimulating hormone (TSH), haemoglobin, ANA and serum ferritin levels were done to rule out other causes of hair loss.
2 ml of blood was collected in grey vacutainer for FBS and 10 ml blood was collected in plain vacutainer for lipid profile, fasting serum insulin, serum testosterone, SHBG, hs-CRP and fibrinogen. 2 ml of blood was collected in lavender vacutainer for ESR. Data regarding sedentariness (physical exercise <30 min) was recorded. CIMT was evaluated using Philips IU-22 and Philips Clear Vue 350 with high frequency (7-12 Hz) linear probe by a radiologist. Carotid artery on each side of the neck were scanned and CIMT was recorded in distal 1 cm of the farther wall of each common carotid artery. The plaques of the extracranial carotid artery were recorded. The six values of the CIMT (three on each side) were obtained and averaged to get the mean CIMT. The pooled data were evaluated using clinical and trichoscopic criteria of FPHL,[8,9] CIMT and cardiovascular risk assessment criteria,[10] WHO classification criteria for Asian population,[11] ATP III criteria for metabolic syndrome,[12] ADA 2017 criteria for diabetes,[13] classification of lipid levels for therapeutic implications,[14] AHA criteria for hs-CRP[15] and HOMA-IR index.[16]
Statistical methodology
The collected data were transformed into variables, coded and entered in Microsoft Excel.
SPSS software version 23 was used for study analysis. Continuous variables were expressed as mean ± standard deviation and median. Categorical variables were expressed as frequencies and percentages and analysed using chi square test. Statistical differences between the categorical data were tested by chi square test or Fisher’s exact test. Kruskal Wallis H test was applied for correlation of Ludwig grade with CIMT and waist circumference. ‘P’ value <0.05 was considered statistically significant.
Results
Subject demographics
Fifty pre-menopausal women were evaluated. Majority of the cases belonged to age groups 18-30 and 31-40 years respectively (44% each). 26 (52%) cases had duration of FPHL between 6 months – 2 years. Family history of patterned hair loss was present in 28 (56%) cases.
Clinico-investigative data
In our study, 44 (88.0%) cases had Ludwig pattern while, 4 (8.0%) cases had Olsen pattern. 2 (4.0%) of the cases had Hamilton pattern. Ludwig grade I [Figure 1] was found in 30 (60%) cases while grades II [Figure 2] and III [Figure 3] were found in 18 (36%) and 2 (4%) cases respectively. We subjectively graded Olsen pattern and Hamilton pattern as Ludwig grade I or II (mild or moderate) based on the clinical severity for statistical correlation. On trichoscopic evaluation, 50 (100%) cases had hair diameter diversity. 47 (94%) cases had miniaturised hair while 30 (60%) cases had yellow dots. Twenty-one (42%) cases had normal BP while 14 (28%) cases had elevated BP, 15 (30%) cases had stage I HTN and none of the cases had stage II HTN. On BMI evaluation, 29 (58%) cases were overweight while 12 (24%) cases were obese. 7 (14%) cases had normal BMI while 2 (4%) cases were underweighted. Majority of the cases, 35 (70%) had waist circumference <88 cm while, 15 (30%) cases had waist circumference ≥88 cm.
Figure 1.
Ludwig grade I
Figure 2.
Ludwig grade II
Figure 3.
Ludwig grade III
Hypercholesterolemia, elevated LDL levels, hypertriglyceridemia and low HDL levels were found in 11 (22%), 31 (62%), 9 (18%) and 17 (34%) cases respectively. 8 (16%) cases were found to be diabetics. Hyperinsulinemia was found in 7 (14%) cases with the mean serum insulin level noted as 16.17 ± 6.81 mIU/l. Elevated testosterone levels were found in 7 (14%) cases with the mean serum testosterone level noted as 16.17 ± 6.81 ng/dl. TSH levels more than 5.6 μIU/L were noted in 3 (6%) cases with the mean TSH level noted as 3.15 ± 1.55 μIU/L. Anemia (hemoglobin (Hb) <12 g/dl) was found in 29 (58%) of the cases with the mean Hb level noted as 11.60 ± 1.18 g/dl. Low ferritin levels were found in 5 (10%) cases with the mean serum ferritin level as 21.12 ± 7.95 (μg/L). ANA was found to be negative in all the cases. ESR was found to be elevated in 43 (86%) cases with mean ESR noted as 31.78 ± 13.87 mm/Hr. We were only able to assess serum fibrinogen and SHBG levels in 49 and 44 patients respectively due to some unavoidable factors. Serum fibrinogen levels were found to be elevated in 9 (18.3%) cases, while low SHBG were found in 18 (40.9%) cases. Elevated hs-CRP levels were found in 21 (42%) cases with the mean hs-CRP level noted as 2.94 ± 2.91 mg/L. CIMT was not found ≥1 mm in any of the cases. 20 (40%) cases had CIMT less than 0.6 mm while 13 (26%) cases had CIMT between 0.6-0.69 mm. 12 (24%) cases had CIMT between 0.7-0.79 mm while 5 (10%) cases had CIMT between 0.8-0.89 mm. Metabolic syndrome was found in 12 (24%) cases. HOMA IR more than 2.9 which was suggestive of significant insulin resistance was found in 17 (34%) cases with the mean HOMA IR value noted as 4.03 ± 2.34. Correlation of CIMT, anthropometric indices (BMI and WC), biochemical markers (serum cholesterol, triglycerides, FBS and fibrinogen) and presence of metabolic syndrome with severity of FPHL in terms of Ludwig grade were found to be statistically significant [Table 1]. Correlation of biochemical markers (LDL, HDL, fasting serum insulin, serum testosterone, SHBG, hs-CRP and ESR) and HOMA IR with severity of FPHL in terms of Ludwig grade were found to be statistically insignificant.
Table 1.
Association between Ludwig grade and parameters
| Parameters | Ludwig grade | P | ||
|---|---|---|---|---|
|
| ||||
| I (n=30) | II (n=18) | III (n=2) | ||
| Age (Years) | 29.60±7.39 | 34.11±7.68 | 34.00±5.66 | 0.1211 |
| Age | 0.5092 | |||
| 18-30 Years | 15 (50.0%) | 6 (33.3%) | 1 (50.0%) | |
| 31-40 Years | 13 (43.3%) | 8 (44.4%) | 1 (50.0%) | |
| 41-45 Years | 2 (6.7%) | 4 (22.2%) | 0 (0.0%) | |
| Occupation | 0.6642 | |||
| Housewife | 15 (50.0%) | 9 (50.0%) | 2 (100.0%) | |
| Service Women | 10 (33.3%) | 8 (44.4%) | 0 (0.0%) | |
| Student | 5 (16.7%) | 1 (5.6%) | 0 (0.0%) | |
| Age Of Onset (Years) | 28.43±7.16 | 32.67±7.66 | 35.00±4.24 | 0.0791 |
| Age Of Onset | 0.4362 | |||
| ≤20 Years | 5 (16.7%) | 1 (5.6%) | 0 (0.0%) | |
| 21-30 Years | 12 (40.0%) | 6 (33.3%) | 0 (0.0%) | |
| 31-40 Years | 12 (40.0%) | 8 (44.4%) | 2 (100.0%) | |
| 41-50 Years | 1 (3.3%) | 3 (16.7%) | 0 (0.0%) | |
| Duration | 0.1532 | |||
| <6 Months | 11 (36.7%) | 2 (11.1%) | 1 (50.0%) | |
| 6 Months - 2 Years | 15 (50.0%) | 10 (55.6%) | 1 (50.0%) | |
| >2 Years | 4 (13.3%) | 6 (33.3%) | 0 (0.0%) | |
| Topical Drug Application (Yes) | 5 (16.7%) | 3 (16.7%) | 0 (0.0%) | 1.0002 |
| Physical Activity (Yes) | 14 (46.7%) | 5 (27.8%) | 1 (50.0%) | 0.3512 |
| Family H/O Patterened Hair Loss (Yes) | 14 (46.7%) | 13 (72.2%) | 1 (50.0%) | 0.1522 |
| Family H/O CAD/HTN/DM (Yes) | 5 (16.7%) | 7 (38.9%) | 1 (50.0%) | 0.1532 |
| Sites: Frontal (Yes) | 18 (60.0%) | 9 (50.0%) | 2 (100.0%) | 0.4692 |
| Sites: Temporal (Yes) | 9 (30.0%) | 5 (27.8%) | 0 (0.0%) | 1.0002 |
| Sites: Vertex (Yes) | 21 (70.0%) | 11 (61.1%) | 2 (100.0%) | 0.5792 |
| Sites: Combination (Yes) | 13 (43.3%) | 8 (44.4%) | 1 (50.0%) | 1.0002 |
| Pattern | 0.5212 | |||
| Ludwig | 25 (83.3%) | 17 (94.4%) | 2 (100.0%) | |
| Olsen | 4 (13.3%) | 0 (0.0%) | 0 (0.0%) | |
| Hamilton | 1 (3.3%) | 1 (5.6%) | 0 (0.0%) | |
| Trichoscopy: Hair Diameter Diversity (Yes) | 30 (100.0%) | 18 (100.0%) | 2 (100.0%) | 1.0003 |
| Trichoscopy: Miniaturised Hair (Yes) | 27 (90.0%) | 18 (100.0%) | 2 (100.0%) | 0.3662 |
| Trichoscopy: Yellow Dots (Yes) | 14 (46.7%) | 14 (77.8%) | 2 (100.0%) | 0.0502 |
| Weight (Kg)*** | 59.30±5.61 | 65.33±10.31 | 72.00±2.83 | 0.0021 |
| Height (cm) | 145.60±39.50 | 156.00±7.71 | 154.00±0.00 | 0.9681 |
| BMI (Kg/m²)*** | 24.41±2.43 | 26.70±3.47 | 30.26±1.05 | 0.0021 |
| BMI*** | 0.0042 | |||
| <18.5 Kg/m2 (underweight) | 1 (3.3%) | 1 (5.6%) | 0 (0.0%) | |
| 18.5-22.9 Kg/m2 (normal) | 5 (16.7%) | 2 (11.1%) | 0 (0.0%) | |
| 23.0-27.49 Kg/m2 (overweight) | 22 (73.3%) | 7 (38.9%) | 0 (0.0%) | |
| ≥27.5 Kg/m2 (obese) | 2 (6.7%) | 8 (44.4%) | 2 (100.0%) | |
| Waist Circumference (cm)*** | 80.60±6.96 | 87.94±6.73 | 90.00±0.00 | <0.0011 |
| Waist Circumference*** | 0.0012 | |||
| <88 cm | 26 (86.7%) | 9 (50.0%) | 0 (0.0%) | |
| ≥88 cm | 4 (13.3%) | 9 (50.0%) | 2 (100.0%) | |
| Pulse Rate (beats/min) | 79.40±4.93 | 77.17±3.54 | 74.00±0.00 | 0.1271 |
| Systolic BP (mmHg) | 120.60±7.20 | 120.61±9.44 | 128.00±0.00 | 0.5411 |
| Systolic BP | 0.4342 | |||
| <120 mmHg | 13 (43.3%) | 8 (44.4%) | 0 (0.0%) | |
| 120-129 mmHg | 12 (40.0%) | 5 (27.8%) | 2 (100.0%) | |
| 130-139 mmHg | 5 (16.7%) | 5 (27.8%) | 0 (0.0%) | |
| Diastolic BP (mmHg) | 76.53±4.31 | 77.94±4.43 | 73.00±4.24 | 0.2971 |
| Diastolic BP | 0.5102 | |||
| <80 mmHg | 24 (80.0%) | 12 (66.7%) | 2 (100.0%) | |
| 80-89 mmHg | 6 (20.0%) | 6 (33.3%) | 0 (0.0%) | |
| BP Category | 0.4162 | |||
| <120 mmHg - <80 mmHg | 13 (43.3%) | 8 (44.4%) | 0 (0.0%) | |
| 120-129 mmHg - <80 mmHg | 8 (26.7%) | 4 (22.2%) | 2 (100.0%) | |
| 130-139 mmHg - 80-89 mmHg | 9 (30.0%) | 6 (33.3%) | 0 (0.0%) | |
| HsCRP (mg/L)*** | 3.20±3.17 | 2.07±2.06 | 6.90±1.98 | 0.0431 |
| HsCRP | 0.1732 | |||
| ≤3 mg/L | 17 (56.7%) | 12 (66.7%) | 0 (0.0%) | |
| >3 mg/L | 13 (43.3%) | 6 (33.3%) | 2 (100.0%) | |
| T. Cholesterol (mg/dl)*** | 157.53±35.67 | 183.61±28.56 | 220.00±0.00 | 0.0031 |
| T. Cholesterol*** | 0.0082 | |||
| <200 mg/dl | 27 (90.0%) | 12 (66.7%) | 0 (0.0%) | |
| ≥200 mg/dl | 3 (10.0%) | 6 (33.3%) | 2 (100.0%) | |
| LDL (mg/dl)*** | 101.13±27.16 | 116.72±26.48 | 154.50±34.65 | 0.0321 |
| LDL | 0.0732 | |||
| <100 mg/dl | 15 (50.0%) | 4 (22.2%) | 0 (0.0%) | |
| ≥100 mg/dl | 15 (50.0%) | 14 (77.8%) | 2 (100.0%) | |
| Triglycerides (mg/dl) | 95.97±27.77 | 120.56±52.82 | 151.00±43.84 | 0.1191 |
| Triglycerides*** | 0.0352 | |||
| <150 mg/dl | 28 (93.3%) | 12 (66.7%) | 1 (50.0%) | |
| ≥150 mg/dl | 2 (6.7%) | 6 (33.3%) | 1 (50.0%) | |
| HDL (mg/dl) | 43.50±10.71 | 44.56±9.51 | 39.50±0.71 | 0.7531 |
| HDL | 0.6872 | |||
| <40 mg/dl | 11 (36.7%) | 5 (27.8%) | 1 (50.0%) | |
| ≥40 mg/dl | 19 (63.3%) | 13 (72.2%) | 1 (50.0%) | |
| FBS (mg/dl)*** | 88.60±6.82 | 117.39±37.40 | 135.00±35.36 | 0.0101 |
| FBS*** | <0.0012 | |||
| <126 mg/dl | 30 (100.0%) | 11 (61.1%) | 1 (50.0%) | |
| ≥126 mg/dl | 0 (0.0%) | 7 (38.9%) | 1 (50.0%) | |
| S. Insulin (mIU/l) | 15.04±6.73 | 17.92±6.87 | 17.40±7.92 | 0.2711 |
| S. Insulin | 0.1252 | |||
| <25 mIU/l | 28 (93.3%) | 13 (72.2%) | 2 (100.0%) | |
| ≥25 mIU/l | 2 (6.7%) | 5 (27.8%) | 0 (0.0%) | |
| S. Testosterone (ng/dl) | 31.51±16.97 | 23.24±13.73 | 24.37±5.14 | 0.2131 |
| S. Testosterone | 0.7762 | |||
| <48 ng/dl | 25 (83.3%) | 16 (88.9%) | 2 (100.0%) | |
| ≥48 ng/dl | 5 (16.7%) | 2 (11.1%) | 0 (0.0%) | |
| TSH (µIU/L) | 2.98±1.53 | 3.40±1.68 | 3.53±0.10 | 0.4881 |
| TSH | 0.6012 | |||
| ≤5.6 µIU/L | 29 (96.7%) | 16 (88.9%) | 2 (100.0%) | |
| >5.6 µIU/L | 1 (3.3%) | 2 (11.1%) | 0 (0.0%) | |
| Hemoglobin (g/dl) | 11.37±1.33 | 11.88±0.83 | 12.60±0.85 | 0.1591 |
| Hemoglobin | 0.1402 | |||
| <12 g/dl | 20 (66.7%) | 9 (50.0%) | 0 (0.0%) | |
| ≥12 g/dl | 10 (33.3%) | 9 (50.0%) | 2 (100.0%) | |
| S. Ferritin (µg/L) | 21.01±6.55 | 20.72±10.23 | 26.50±3.54 | 0.4681 |
| S. Ferritin | 0.4742 | |||
| <11 µg/L | 2 (6.7%) | 3 (16.7%) | 0 (0.0%) | |
| ≥11 µg/L | 28 (93.3%) | 15 (83.3%) | 2 (100.0%) | |
| ANA (Positive) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 1.0003 |
| SHBG (nmol/L) | 27.63±20.02 | 29.90±19.56 | 23.48±10.42 | 0.8681 |
| SHBG | n=26 | n=16 | n=2 | 1.0002 |
| <18 nmol/L | 11 (42.3%) | 6 (37.5%) | 1 (50.0%) | |
| ≥18 nmol/L | 15 (57.7%) | 10 (62.5%) | 1 (50.0%) | |
| Fibrinogen (mg/dl)*** | 295.60±57.59 | 371.12±116.31 | 401.00±77.78 | 0.0301 |
| Fibrinogen*** | n=30 | n=17 | n=2 | 0.0222 |
| <400 mg/dl | 28 (93.3%) | 11 (64.7%) | 1 (50.0%) | |
| ≥400 mg/dl | 2 (6.7%) | 6 (35.3%) | 1 (50.0%) | |
| ESR (mm/Hr) | 29.33±15.91 | 35.22±9.47 | 37.50±10.61 | 0.1281 |
| ESR | 0.0612 | |||
| <20 mm/Hr | 7 (23.3%) | 0 (0.0%) | 0 (0.0%) | |
| ≥20 mm/Hr | 23 (76.7%) | 18 (100.0%) | 2 (100.0%) | |
| CIMT (Right) (cm)*** | 0.06±0.01 | 0.07±0.01 | 0.07±0.01 | 0.0071 |
| CIMT (Left) (cm)*** | 0.06±0.01 | 0.07±0.01 | 0.08±0.01 | 0.0011 |
| CIMT (Average) (cm)*** | 0.06±0.01 | 0.07±0.01 | 0.08±0.01 | 0.0011 |
| CIMT (Right)*** | 0.0082 | |||
| <0.06 cm | 15 (50.0%) | 2 (11.1%) | 0 (0.0%) | |
| 0.06-0.069 cm | 7 (23.3%) | 5 (27.8%) | 1 (50.0%) | |
| 0.07-0.079 cm | 7 (23.3%) | 6 (33.3%) | 0 (0.0%) | |
| 0.08-0.089 cm | 1 (3.3%) | 5 (27.8%) | 1 (50.0%) | |
| CIMT (Left)*** | 0.0012 | |||
| <0.06 cm | 14 (46.7%) | 2 (11.8%) | 0 (0.0%) | |
| 0.06-0.069 cm | 10 (33.3%) | 2 (11.8%) | 0 (0.0%) | |
| 0.07-0.079 cm | 3 (10.0%) | 5 (29.4%) | 0 (0.0%) | |
| 0.08-0.089 cm | 2 (6.7%) | 6 (35.3%) | 1 (50.0%) | |
| 0.09-0.099 cm | 1 (3.3%) | 2 (11.8%) | 1 (50.0%) | |
| CIMT (Average)*** | 0.0012 | |||
| <0.06 cm | 18 (60.0%) | 2 (11.1%) | 0 (0.0%) | |
| 0.06-0.069 cm | 7 (23.3%) | 6 (33.3%) | 0 (0.0%) | |
| 0.07-0.079 cm | 4 (13.3%) | 7 (38.9%) | 1 (50.0%) | |
| 0.08-0.089 cm | 1 (3.3%) | 3 (16.7%) | 1 (50.0%) | |
| Metabolic Syndrome (Yes)*** | 1 (3.3%) | 9 (50.0%) | 2 (100.0%) | <0.0012 |
| HOMA - IR*** | 3.20±1.53 | 5.27±2.94 | 5.45±1.06 | 0.0051 |
| HOMA - IR Category | 0.0592 | |||
| ≤2.9 | 14 (46.7%) | 3 (16.7%) | 0 (0.0%) | |
| >2.9 | 16 (53.3%) | 15 (83.3%) | 2 (100.0%) | |
***Significant at P<0.05, 1: Kruskal Wallis Test, 2: Fisher’s Exact Test, 3: Chi-Squared Test
Discussion
In majority of the Indian studies,[2,3,4,5,6,7,17,18,19] the most common age of presentation was noted to be between 30 to 40 years with the mean age of onset around 30 years of age which was similar to our study. Our patients belonged to 2nd and 3rd decade. Though few previous studies[17,18] have concluded that the prevalence of FPHL increases with advancing age, a similar trend was not observed in our study. This could be attributed to the fact that the study was hospital based in an urban area where patients hold great importance for body image and cosmetic appeal. However, due to small sample size and lack of control group, the true significance of this parameter cannot be assessed properly.
The duration of hair fall was between 6 months to 2 years in majority of the cases in our study, although it is quite short as compared to other Indian studies.[2,19] 56% of cases in our study had family history of patterned hair loss and there was no significant difference in the age of onset of FPHL between the cases with positive family history (28.93 ± 6.81) and those with no family history (31.86 ± 8.14). There was no significant association noted between family history and severity of FPHL. ((χ2 = 3.012, P = 0.152)). Similar findings were noted by Ravikaran SP et al.[2] Study conducted by Zhang X et al.[20] and Okram S et al.[21] reported an association between an early age of onset and advanced grade of hair loss in patients with family study. Hence this high prevalence of family history, with varying degrees of intensity of hair loss and the onset at different stages, suggest a polygenic pattern of inheritance with incomplete penetrance. Similar to our study, majority of Indian and international studies[5,19,21,23] have so far noted Ludwig pattern (stage I and II) to be the most common pattern at presentation.
Elevated BP was present in 28% of the cases in our study. 30% of the cases had Stage I HTN. In majority of the studies,[5,22,23] there was significant difference in systolic and diastolic BP in FPHL cases and controls. In our study, 30% of the cases had waist circumference ≥88 cm and remaining had <88 cm. There was significant association between WC and severity of FPHL (Ludwig grade) (χ2 = 16.180, P ≤ 0.001) with the mean WC being highest in Ludwig grade III. In international studies by Arias-Santiago S et al.[5] and Agamia N et al.,[23] a higher mean WC was noted in FPHL cases as compared to controls. 58% of the cases were overweight in our study and 24% of the cases were obese. There was a significant association between BMI and severity of FPHL (Ludwig grade) (χ2 = 15.975, P = 0.004). No correlation between BMI and FPHL was reported in other studies. In majority of the studies, dyslipidemia was found significantly more in FPHL cases as compared to controls. Due to lack of control group, we were not able to assess the significance of the above parameter properly, however we found significant association between hypercholesterolemia and triglyceridemia with the severity of FPHL (Ludwig grade). 16% of the patients were found to be diabetics in our study and a significant association between the level of FBS and severity of FPHL was found. 14% of the cases were found to have hyperinsulinemia. However, In an Indian study by Dharam Kumar KC, et al.,[22] mean FBS level was not found to be significantly higher in FPHL cases as compared to controls (P > 0.05). 66.0% of the cases in our study had HOMA I IR category >2.9 suggestive of significant insulin resistance. There was no significant association of HOMA IR with the clinical severity of FPHL. No Indian study till date has evaluated the association between FPHL and insulin resistance by HOMA IR.
ESR was found to be elevated in 80% of the cases, but did not correlate with FPHL severity. Hyperfibrinogenemia was found in 20% of the cases which was significantly associated with severity of FPHL (Ludwig grade) (χ2 = 7.323, P = 0.022). lower levels of SHBG (<18 nmol/L) were found in 40.9% of the cases. It gives free testosterone that can exert its action at peripheral level,[24] thus affecting cardiovascular risk. Raised levels of hs-CRP (>3 mg/dl) were found in 42.0% of the cases. Majority of international studies[5,23] have noted significantly higher value of fibrinogen, hsCRP and low value of SHBG in FPHL cases as compared to control. MetS was found in 24% of the cases and was significantly associated with the severity of FPHL (Ludwig grade) (χ2 = 20.029, P = <0.001). In a study by Dharam Kumar et al.,[22] the prevalence of MetS in cases (53%) was statistically very highly significant when compared to controls (17%) (P < 0.001).
Our study is a pilot Indian study to evaluate the role of hs CRP and correlation between CIMT and FPHL [Table 2].
Table 2.
Review of studies with comparative evaluation of outcomes
| Author/Time/Place | Subjects/study type | Parameters studied | Results |
|---|---|---|---|
| Our study | • 50 Female patients with FPHL • Observational study |
• BMI, WC and BP • FBS, lipid profile, ferritin, S.testosterone, Fibrinogen, SHBG, hs CRP and ESR • Usg doppler for CIMT and atheromatous plaques |
• Significant no. of patients showed raised BP, WC, BMI, fasting hyperglycaemia, high HOMA IR, deranged lipid profile, low SHBG, high hs-CRP, elevated ESR and fibrinogen level. • Metabolic syndrome was found in significant number (24%) of patients. An association was also found between these parameters including CIMT and clinical severity of FPHL. |
| Patil VB et al.,[29] 2019, Karnataka, India | • 219 female patients with CAD and 219 sex matched controls without CAD • Retrospective case control stusy |
• Pattern and grade of FPHL, family H/O FPHL and CVD • BP, DM and S. Cholesterol |
• Association between FPHL and CAD statistically significant. • Age and HTN predominant factors for CAD Lipid profile not statistically significant in both groups |
| Dharam Kumar KC, et al.[22] 2018, Bangalore, India | • 64 male AGA cases and controls; 36 FPHL cases and sex matched controls • Case control study |
• BP, Lipid profile, FBS, WC | • MetS prevalence : cases (53%) and controls (17) (P<0.001) • SBP and TG statistically significant between cases and controls • DBP, FBS and HDL not statistically significant in both the groups |
| El Sayed MH et al.,[25] 2016, Egypt | • 45 FPHL cases and45 age and sex matched controls • Case control study |
• Anthropometric indices (BP and WC) • FBS and fasting lipid profile |
• MetS prevalence : cases (68.9) and controls (20%) (P<0.001) • Association of MetS and WC with FPHL severity significant |
| Agamia N et al.,[23] 2015, Eygpt | • 50 (38 males and 12 females with AGA) cases and 50 controls • Case control study |
• BMI, WC and BP • FBS, lipid profile, SHBG, fibrinogen, ESR, CRP, S. testosterone and HOMA IR |
• MS prevalence: FPHL (25%), male AGA (47.4%) and 37.7% of controls. (P<0.0001) • FBS and fribrinogen statistically significant between FPHL and cases. (P<0.05) |
| Arias-Santiago S, et al.,[5] 2010, Spain | • 77 AGA cases (40 male and 37 females) and 77 controls • Case control study |
• BMI, WC and BP • S. aldosterone, FBS, lipid profile, S. testosterone, insulin, SHBG, D-dimer, fibrinogen, ESR and CRP • Doppler USG for CIMT % atheromatous plaques |
• Atheromatous plaques and CIMT >1.5 cm: FPHL (27%), male AGA (32.5%) and controls (7.8%) • MS prevalence: FPHL (48.5%), male AGA (60%) and 10.4% of controls. (P<0.0001) • Insulin, FBS, HOMA IR and SHBG statistically significant between FPHL and cases. (P<0.05) • CRP, fibrinogen, D-dimer statistically significant between FPHL and cases. (P<0.05) |
Although, a significant association was found between mean CIMT and severity of FPHL, none of the cases had atheromatous plaques or CIMT ≥1 mm. Arias-Santiago S et al.[5] detected atheromatous plaques and (CIMT >1 cm) in 32.5% of male patients with AGA versus 7.5% of male control subjects and 27% of female patients with AGA versus 8.1% of female control subjects (P = 0.032). The prevalence of MetS in cases in FPHL (48.6%) was highly significant when compared to healthy controls. The mean age (years) of patients presented with FPHL in their study was 48.18 ± 9.7, while in our study the mean age was 31.40 ± 7.64. El Sayad MH et al.[25] reported association of metabolic syndrome with severity of FPHL similar to our study, which was not noted by Agamia N et al.[23] Mansouri P et al.[26] performed coronary catheterization in 106 female patients younger than 55 years. The correlation of AGA and coronary artery disease (CAD) and AGA and previous history of myocardial infarction were statistically significant (P < 0.05). Similar to this study, an Indian study conducted by Patil VB, et al.[29] on 438 women within 55 years of age who were admitted for coronary angiography. AGA was diagnosed in 40.18% of the case group. A statistically significant association was observed between the development of FPHL in CAD participants (P < 0.0001). In addition, a high percentage of FPHL Ludwig grade III participants were diagnosed with triple vessel disease (TVD), which can be an indicator for the heart condition.
Apart from the small sample size, lack of control group and ethnic background, the difference in the result between this study and our study could also be explained by the difference in the age of the patients included in the study as the thickness of intima of carotid artery increases with age, gender and ethnicity.[28] It is quite difficult to assess CIMT values because in addition to risk factors, the absolute CIMT value also depends on the location of the measurement (segments, near, or far wall), the ultrasound equipment used, and off line reading system (automated, manual tracings) employed.[29]
Conclusion
This was a pilot study from India to assess CIMT, levels of hs CRP and fibrinogen in patients of FPHL. More studies with larger sample size are required to validate our results. CIMT and acute phase reactants (hs-CRP, ESR and fibrinogen) are markers of chronic inflammation and atherosclerosis, their elevated levels in patients of FPHL point towards an increased risk for atherosclerosis and cardiovascular disorders and timely interventions like lifestyle modification, antihypertensives or lipid lowering therapy may improve the long-term prognosis of CVD in this high-risk population.
Larger multicentric studies should be undertaken to validate our findings and establish the association between FPHL and cardiovascular risk factors.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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