Trichoscopic Assessment of treatment outcomes with Topical MINOXIDIL, Oral MINOXIDIL, And Topical MINOXIDIL in combination with Oral FINASTERIDE in MALE ANDROGENETIC ALOPECIA and its association with Insulin resistance

TITLE TRICHOSCOPIC ASSESSMENT OF TREATMENT OUTCOMES WITH TOPICAL MINOXIDIL ORAL MINOXIDIL AND TOPICAL MINOXIDIL IN COMBINATION WITH ORAL FINASTERIDE IN MALE ANDROGENETIC ALOPECIA AND ITS ASSOCIATION WITH INSULIN RESITANCE

INTRODUCTION Androgenetic alopecia AGA is one of the most common causes of hair loss in both sexes  with a higher incidence reported generally in men The development and occurrence of AGA depends on multiple factors such as genetic predisposition endocrine and metabolic factors and exogenous causes In male patients hair loss typically involves temporal and vertex region sparing the occiput In India a prevalence rate of 58 percent in males aged 30 to 50 years has been found for AGA In all cases the incidence gradually increases with age The pathophysiology of AGA is due to elevated dihydrotestosterone DHT production increased levels of 5 alpha reductase and an increase in androgen receptors in the areas of the scalp affected by balding  This heightened androgenic milieu in the scalp contributes to the progressive miniaturization of hair follicles by shortening the anagen, or growth phase within the normal hair growth cycle which instigates follicular miniaturization There is a gradual conversion of

terminal hairs into indeterminate and finally into vellus hairs AGA may also be associated with hyperinsulinemia brought on by insulin resistance which can reduce Sex Hormone Binding Globulin SHBG concentrations by increasing free androgen levels Hair follicles vulnerable to androgenetic alopecia AGA might experience progressive follicular shrinkage and loss because of Insulin Resistance  Standard methods used to diagnose hair disorders are clinical inspection pattern of hair loss pull test  trichogram biopsy and screening blood tests They vary in sensitivity reproducibility and invasiveness Trichoscopy is very useful for diagnosis of scalp and hair disorders and can greatly improve clinical management Structures which may be visualized by trichoscopy include hair shafts hair follicle openings perifollicular epidermis and cutaneous microvessels Recent studies have accumulated evidence that the use of trichoscopy in the clinical evaluation of hair disorders improves diagnostic capability beyond simple clinical inspection Trichoscopy offers reproducible and quantifiable data making it superior to subjective grading alone On Trichoscopy in AGA we see hair shaft thickness heterogeneity anisotrichosis that is the transformation of terminal hair into vellus hair which is the miniaturization process in evolution which forms the basis of AGA pathogenesis Anisotrichosis higher than 20 percent is an essential criterion for the diagnosis of AGA  In the scalp follicular units usually contain 2 to 4 terminal hairs and 1 to 2 vellus hairs Fewer hairs per follicle is a characteristic feature of AGA Empty follicles which are seen as yellow dots trichoscopically are also present along with other signs such as perihilar sign In men the most accepted grading system for AGA is the modified Norwood Hamilton classification AGA according to the Hamilton Norwood scale is classified clinically into seven major stages Stage 1 no hair loss Stage 2 Receding of the fronto temporal hairline Stage 3 to 4 Regression of the frontal hairline and balding of frontal and vertex scalp areas Stage 5 to 6 Confluence of the affected areas Stage 7 Only an occipitotemporal hair crown persisting Currently there are only two US Food and Drug Administration approved drugs for the condition topical minoxidil and oral finasteride A study performed by Johnson H et al showed that even though both Finasteride and Minoxidil are well established monotherapies with multiple studies and guidelines supporting their utility combined therapy particularly with topical minoxidil and oral finasteride has shown to have additive effects

OBJECTIVES

To evaluate treatment outcomes in Androgenetic Alopecia using trichoscopy by comparing

Group a topical Minoxidil Group b oral Minoxidil Group c topical Minoxidil with oral Finasteride

To evaluate the association between Insulin Resistance and grade of

Androgenetic Alopecia

METHODOLOGY

Study setting Outpatients presenting to the dermatology OPD

Study design It’s a time bound institution based longitudinal observational study Study participants Male patients with Androgenetic Alopecia

Inclusion criteria

Male patients above 18 years of age who have AGA and are willing to provide informed consent

Patients who have not started treatment or on Topical Minoxidil Oral Minoxidil or Topical Minoxidil with Oral Finasteride for one month or less.

Exclusion criteria

Patients on any treatment for AGA for more than 1 month before participating to the study

Patients with already diagnosed systemic diseases like diabetes mellitus malignancy uncontrolled hypertension or hypotension psychiatric illness uncontrolled thyroid disorder

Patients having other forms of Alopecia

Patients who have undergone hair restoration surgeries previously

Patients on antimetabolites

Sample size TIME  BOUND SAMPLING

(Estimated sample size 117) Sample size was calculated using G power software multigroup goodness fit by using Annamreddy L et al article as reference For the current study the sample size is estimated for an effect size of 0.5 with level of significance of 0.05 and a power of 0.8 as 117 individuals  As there are three groups we have 39 individuals in each of the three groups

Sampling method Convenience sampling of eligible patients presenting to the Dermatology Outpatient Department Tool for data collection

Proforma including Norwood-Hamilton grading and clinical photographs maintaining patient privacy for Modified Global Photographic Assessment

Trichoscopy using DermLite DL5© at 10-fold magnification

Data collection methodology

Following approval patients visiting dermatology outpatients with Androgenic Alopecia fulfilling the inclusion and exclusion criteria will be given participant information sheet about the study They will be recruited following informed consent

Relevant history will be recorded Baseline demographic clinical and anthropometric details will be recorded Value of fasting blood sugar that is done as a standard treatment will be obtained and the left over plasma of the previous test will tested to check for Insulin Resistance to calculate HOMA IR Baseline hair pull test and Hamilton Norwood classification grading will be done and documented Baseline ECG evaluation which will be done for all patients as part of Minoxidil treatment will be noted

Participants will be enrolled into one of three groups based on dermatologist prescribed therapy

Group A Topical Minoxidil 5 percent twice daily Group B Oral Minoxidil 2.5mg per day Group C Topical Minoxidil 5 percent once a day with Oral Finasteride 1mg per day Trichoscopic assessment will be done to look for

hair diameter density single hair follicular units  Follicular findings like yellow dots Scalp findings such as honeycomb pigmentation Perifollicular findings such as brown perihilar sign Serial digital camera photographs will be taken and stored in a hard drive assessment will be done using Modified Global Photographic Assessment Score

Follow up Assessments will include a total of four follow ups after a baseline evaluation on day 0 at 1 month 2 months 3 months and 4 months for trichoscopic evaluation and to calculate the Modified Global Photography Assessment Score Adverse events such as but not limited to irritant contact dermatitis headache low blood pressure will be documented at each follow up Blood Pressure evaluation will be done at each follow up Patient reported outcomes and therapy adherence will be documented at each follow up Pull test and Norwood Hamilton grading will be repeated after baseline evaluation on last visit

Test procedure

Trichoscopy for objective assessment of hair parameters

Fasting blood glucose will be done in Central Lab as per standard treatment  Value of test and leftover sample will be collected from the Central lab The plasma will be separated and stored at minus 80 C in the Central Research Lab until further analysis Plasma Insulin will be estimated using ELISA kits from commercial sources on ELX800 ELISA reader HOMA IR will be calculated Patients with HOMA IR more than or equal to 2.5  will be classified as insulin resistant Subgroup analysis will be done

Outcome variables

Primary Outcomes

To look for trichoscopic improvement in parameters hair diameter

Density  single follicular units  perifollicular pigmentation yellow dots

honeycomb pigmentation

Treatment outcomes and grade of improvement according to the

Hamilton Norway grading in each treatment arm

Correlation between insulin resistance and AGA severity

Improvement in Modified Global Photographic Assessment Score over

time

Secondary Outcomes Patient satisfaction grades over time

Biological materials required Left over plasma sample after standard fasting glucose testing

Data analysis The data will be entered in the Microsoft excel spreadsheet and analysed using SPSS software version 29 Data will be presented as means standard deviation and percentages The comparative analysis of trichoscopic improvement of Androgenetic Alopecia will be assessed using Chi square test and p value less than 0.05 will be considered significant

IMPLICATIONS

This study aims to provide real-world comparative trichoscopic data on standard Androgenetic Alopecia therapies It may help identify improvement seen trichoscopically amongst the treatment arms much earlier compared to subjective assessment by the patient This study also offers insight into systemic factors like insulin resistance that could impact prognosis and long term disease control