Months Of Isotretinoin Treatment Research Articles

Analysis of Isotretinoin-Induced Alterations in the Levels of Plasma Trace Elements: Investigation of the Relationship Between Magnesium, Phosphorus, Potassium, Zinc, and Treatment-Related Side Effects.

Isotretinoin is an effective treatment against acne vulgaris, but it also causes many side effects during and after the treatment. The relationship between the changes in the levels of plasma trace elements of patients with AV after 3months of isotretinoin treatment and the side effects was investigated in the study. Plasma samples of 35 patients were collected before and after isotretinoin treatment. Samples were analyzed by Inductively Coupled Plasma-Mass Spectrometer. After treatment, the levels of phosphorus, magnesium, and zinc in plasma increased statistically, while the level of potassium decreased (p < 0.05). The treatment had differing effects on zinc levels based on the gender of the individuals. With treatment, the levels of zinc in the plasma of men showed a greater increase compared to women (p = 7.3e-04). Additionally, the correlation matrix analysis revealed a strong correlation (R > 0.8) between magnesium and calcium. According to the study results, the change in phosphorus and potassium levels shows that isotretinoin affects kidney functions. The results suggest that phosphorus, potassium, magnesium, and zinc are associated with fatigue, dry skin and chapped lips, hair loss, and sebum secretion, respectively. Consequently, the study emphasizes the need for a comprehensive pre-treatment assessment, including monitoring of liver and kidney function as well as the levels of phosphorus and potassium in patients.

Evaluation of hematological parameters in patients using systemic isotretinoin with diagnosis of acne vulgaris.

Oral isotretinoin is the most effective treatment option in patients with acne. However, it can cause various hematologic and biochemical abnormalities. This study aimed to evaluate hematologic abnormalities during oral isotretinoin treatment in patients with acne. In this cross-sectional study, the hematologic and inflammatory parameters of 138 patients with acne using 0.3-1 mg/kg/day oral isotretinoin for at least 6months were retrospectively analyzed. In the study, the female-to-male ratio was 2.83, and the mean age of the patients was 23.1 ± 5.8 years. At the third and sixth months of isotretinoin treatment, there was a statistically significant decrease in the neutrophil count compared to the pre-treatment values (p=0.003 and p=0.032, respectively). The platelet count showed the most statistically significant increase (p < 0.001) at the first month of treatment. The most statistically significant decrease in the neutrophil-to-lymphocyte ratio (NLR) was observed at the third month of treatment (p < 0.001). No significant changes were observed in hemoglobin, hematocrit, white blood cell count, mean corpuscular volume, and mean platelet volume. There was a decrease in neutrophils and NLR and an increase in platelets during isotretinoin treatment, and these changes were usually mild. However, it would be appropriate to monitor blood counts during treatment in patients with neutropenia or thrombocytosis.

Investigation of systemic immune-inflammation index and systemic inflammation response index as an indicator of the anti-inflammatuary effect of isotretinoin in patients with acne vulgaris

Purpose Oral isotretinoin (ISO) can effect markers of inflammation in patients with acne vulgaris. Systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) were described as novel inflammatory and prognostic biomarkers. The present study aimed to evaluate the effectiveness of SII, SIRI, and other inflammatory markers in patients with acne vulgaris who receive isotretinoin therapy. Methods One hundred fifty-six patients with moderate-to-severe acne vulgaris who received at least 3 months of ISO treatment (0.5–1 mg/kg/day) and 100 healthy individuals were enrolled in the study. The medical records and laboratory findings of the participants were reviewed retrospectively. Pre-treatment and post-treatment neutrophil, lymphocyte, monocyte, and platelet counts, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), SII, SIRI, total cholesterol, LDL cholesterol, triglyceride, HDL cholesterol, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were analysed. Results Before ISO treatment, patients with moderate-to-severe acne vulgaris had significantly higher platelet counts than healthy controls (p = 0.003). Serum total cholesterol, LDL, triglyceride, AST, and ALT increased significantly after isotretinoin treatment in patients with acne vulgaris (p < 0.001, p < 0.001, p < 0.001, p < 0.001, p = 0.029, respectively). In the follow-up of patients using ISO, a significant increase was found in platelet levels (p < 0.001). However, neutrophil, NLR, SII, and SIRI were found significantly decrease after ISO treatment (p = 0.047, p = 0.038, p = 0.003, p = 0.001; respectively). Lymphocyte, monocyte, PLR, and MLR did not show any significant change after ISO treatment. Conclusion SII and SIRI are better parameters as an indicator of the anti-inflammatory effect of isotretinoin than other inflammatory markers.

A Novel Inflammatory Marker in the Follow-up of Moderate-to-Severe Acne Vulgaris Administered Isotretinoin: Systemic Immune-Inflammation Index (SII).

Background: Systemic immune-inflammation index (SII) is calculated by multiplying the neutrophil-lymphocyte ratio (NLR) and the platelet count. In this study, we aimed to investigate the difference of SII and other inflammatory markers in patients with acne vulgaris compared to healthy controls and themselves after Oral isotretinoin (ISO) treatment. Materials and methods: In this study 190 patients with severe acne vulgaris who received at least 3 months of ISO treatment (0.5-1mg/kg/day) and 66 healthy individuals were evaluated. Hemoglobin, neutrophil, lymphocyte, monocyte, and platelet counts, mean platelet volume (MPV), Plateletcrit (PCT), NLR, platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), and SII were analyzed. Results: Before ISO treatment, patients with moderate-to-severe acne vulgaris had significantly higher neutrophil counts and SII levels than healthy controls (p=0.036, p=0.028; respectively). In the third month of ISO treatment, both neutrophil count and SII level were similar to healthy control (p=0.376, p=0.379; respectively). In the follow-up of patients using ISO, a significant decrease was observed especially in SII levels (p=0.037). Although the lymphocyte count was not significantly different from the control group before treatment, it increased significantly after ISO and was significantly higher than both the control and pretreatment period (p=0.134, P=0.026, p=0.017; respectively). Although NLR was not different from control in the pre- and post-treatment period, the change in neutrophil and lymphocyte counts after treatment caused a statistically significant decrease in NLR (p=0.682, p=0.289, p=0.043; respectively). Conclusions: We believe that SII is a more useful parameter as an indicator of the anti-inflammatory effect of isotretinoin.

Evaluation of hirsutism and hormonal parameters in acne vulgaris patients treated with isotretinoin.

Although the effect of isotretinoin use on hormonal changes in acne pathogenesis is not fully known, there are limited studies on its effects on the development of hirsutism. In this study, it was aimed to evaluate the effect of isotretinoin use on hirsutism and hormonal parameters in patients with acne vulgaris. In this study, 30 female acne patients and 30 healthy females were evaluated prospectively. Menstrual irregularity, LH, FSH, prolactin, progesterone, 17-OH progesterone, oestradiol, total testosterone, DHEA-S, insulin, glucose, TSH levels, Ferriman-Gallwey (FG) score and ultrasonography (USG) findings of control group and patient group were recorded. Pre-treatment progesterone (P=.007) and oestradiol (P=.001) levels of the patients were statistically lower than the control group. In the patient group, menstrual irregularity (P<001) and FG hirsutism score at the third month of treatment were significantly higher than before treatment. In 10% of the patients, there were abnormal findings on pelvic USG in the third month of treatment. In our study, it could not be revealed that isotretinoin has a significant effect on pituitary, adrenal hormones and insulin resistance. We found that 3months of isotretinoin treatment caused an increase in menstrual irregularity and FG hirsutism score.

Effect of isotretinoin treatment on the inflammatory markers in patients with acne vulgaris: can monocyte/HDL be a new indicator for inflammatory activity of isotretinoin treatment?

Background: Oral isotretinoin (ISO) can effect markers of inflammation in patients with acne vulgaris. To our knowledge, there are no data on the relationship between ISO and monocyte to HDL cholesterol ratio (MHR). In this study, it is aimed to examine the effect of the ISO treatment on the MHR and other inflammatory markers in patients with acne vulgaris.Materials and methods: In this study, 89 out of 120 patients with severe/very severe acne vulgaris according to the Global Acne Grading Scale who received at least 3 months of ISO treatment were evaluated. The complete blood counts including mean levels of mean platelet volume, plateletcrit (PTC), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), MHR, and serum biochemistry panel were evaluated before and after ISO treatment.Results: The mean platelet value, NLR, and PLR levels underwent a statistically significant decrease after ISO treatment (p < 0.05) while MHR increased significantly 3 months after ISO treatment (p = 0.017). The mean platelet value, NLR, and PLR levels were 9.56 ± 1.05, 2.15 ± 0.81, and 142.45 ± 48.33 before treatment while were 9.32 ± 1.45, 1.90 ± 0.99, and 127.94 ± 41.38 after treatment, respectively. On the other hand, MHR was 9.76 ± 4.27 and 10.86 ± 4.12 before and after treatment, respectively.Conclusions: In this study, we found that ISO may have both inflammatory and anti-inflammatory effects by using MPV, PTC, NLR, PLR, and MHR. The inflammatory effects of ISO may be associated with possible inflammatory diseases. MHR can be used as a novel marker to investigate the inflammatory effect of the ISO.

Plasma dermcidin levels in acne patients, and the effect of isotretinoin treatment on dermcidin levels.

Acne vulgaris is a chronic inflammatory disease of the pilosebaceous unit. Dermcidin (DCD) is an antimicrobial peptide released from eccrine sweat glands and sebaceous glands. Studies investigating the role of DCD expression in acne development are scarce. The aim of this study was to determine the relationship between DCD expression and acne vulgaris and the effect of oral isotretinoin treatment on DCD levels. Two groups (one patient group and one control group) were included in the study. The patient group consisted of 30 patients with acne vulgaris who were given oral isotretinoin treatment for 6 months until the cumulative dose was attained. Plasma DCD levels were investigated before and 6 months after treatment. The control group comprised 30 volunteer individuals without acne vulgaris or any inflammatory dermatosis. Of the patients, 24 (80%) had Grade 3, 3 (10%) had Grade 1, and 3 (10%) had Grade 4 acne vulgaris, as determined according to the Pillsbury scoring method. The DCD levels in the control group were significantly higher than those in pretreatment patients (39.53 ± 20.2 vs. 28.60 ± 20.12, p = .004). Additionally, pretreatment DCD levels were significantly increased after 6 months of isotretinoin treatment in the patient group (28.60 ± 20.12 vs. 35.07 ± 24.02, p = .012). The mean pretreatment global acne grading system score of 20.86 ± 4.43 was decreased to 5.17 ± 1.91 in patients after treatment (p < .001). This study indicated that DCD plays an important role in the pathogenesis of acne. It demonstrates anti-inflammatory properties in acne vulgaris. Moreover, it was shown that isotretinoin treatment may improve acne vulgaris by increasing DCD levels.

The effect of isotretinoin on insulin resistance and adipocytokine levels in acne vulgaris patients

Background/aim Recent data draw attention to the effect of body composition, insulin resistance, and adipocytokines to acne vulgaris (AV) development. The aim of this study was to assess the association of AV with insulin resistance and adipocytokine levels and to evaluate the effect of isotretinoin on insulin resistance and adipocytokine levels. Materials and methods In 29 AV patients and 29 healthy volunteers, body mass index (BMI) and body fat mass (BFM), lipid, adiponectin, leptin, resistin, retinol binding protein-4 (RBP4), and insulin levels were measured and insulin resistance was assessed by HOMA-IR index in serum samples taken twice from patients before and after isotretinoin treatment.ResultsIn AV patients, pretreatment HOMA-IR and adipocytokine levels were not found to correlate with disease severity. With five months of isotretinoin treatment, higher HOMA-IR values ​​were found (P = 0.028). Isotretinoin therapy maintained lower mean resistin levels (P = 0.016), higher mean RBP4 levels (P = 0.040), but not affected the mean adiponectin and leptin levels (P = 0.113, P = 0.125, respectively).ConclusionsAll data suggests that five months of isotretinoin therapy in AV patients causes insulin resistance and the increase in insulin resistance is not dependent on age, BMI, BFM, and lipid levels of these patients.

Suppressed Adiponectin Levels and Increased Adiponectin Response to Oral Glucose Load in Lean Women with Severe Acne Normalizes after Isotretinoin Treatment

Background/Aim: Isotretinoin, the drug of choice for severe acne, might be associated with a decrease in insulin sensitivity. Adiponectin is an adipose tissue-derived protein that increases insulin sensitivity. In this study, we aimed to investigate adiponectin levels in postadolescent severe acne and the effect of isotretinoin on adiponectin levels. Methods: Participants included 18 female patients with severe acne and 18 healthy women matched for age and body mass index (BMI). Acne patients completed a 6-month isotretinoin treatment. Anthropometric measurements, serum adiponectin, lipids, fasting glucose, fasting insulin, and homeostatic model assessment for insulin resistance (HOMA-IR) were determined, and a standard 2-h oral glucose tolerance test (OGTT) was performed in healthy women once and in patients with acne before and after treatment. Results: At baseline, patients with acne had significantly lower serum adiponectin levels than controls. Isotretinoin treatment resulted in a significant increase in weight, BMI, and triglyceride and adiponectin levels. Glucose metabolism markers in patients with acne and controls were similar at baseline and did not change after treatment. Baseline OGTT in acne patients revealed an increased adiponectin response at 2 h, which was not present in healthy controls. Remarkably, this OGTT-induced adiponectin increment in acne patients was diminished after isotretinoin treatment. Conclusion: Adiponectin levels are differently regulated in women with severe acne and healthy controls in that circulating basal levels in patients are suppressed and show an increase in response to oral glucose load. Suppression of baseline adiponectin ameliorates after 6 months of isotretinoin treatment, reaching levels similar to those of healthy controls.

The Effect of Isotretinoin on Retinol-Binding Protein 4, Leptin, Adiponectin and Insulin Resistance in Acne Vulgaris Patients

Background: The effect of isotretinoin (ISO) on adipokines and insulin resistance has been investigated in a few studies, and the results are conflicting. Objective: The aim of this study was to investigate the effect of ISO treatment on insulin resistance and adipokines. Methods: Thirty-three patients with acne vulgaris and a control group of 30 healthy volunteers were included in our study. Screening for the biochemical parameters was performed just before the initiation and after 3 months of ISO treatment. Results: In the acne group, basal leptin levels were significantly lower (p = 0.003) and basal adiponectin levels significantly higher (p = 0.008) compared with the control group. After ISO treatment, leptin levels (p = 0.0005) decreased and adiponectin levels (p = 0.003) increased significantly. However, measurements of fasting blood glucose, insulin, C peptide, retinol-binding protein 4 (RBP4), homeostasis model assessment insulin resistance and BMI did not differ after ISO treatment. Conclusion: ISO may affect leptin and adiponectin levels. It does not, however, affect insulin resistance and RBP4 levels.

Oral isotretinoin therapy of acne patients decreases serum paraoxonase-1 activity through increasing oxidative stress

Objectives: There are only a few earlier studies suggesting relationship between isotretinoin treatment and oxidative stress however, their results are conflicting. Therefore we aimed to concretize the influence of isotretinoin treatment on oxidant/antioxidant status together with paraoxonase-1 (PON1) activity for the first time. Methods: The study was performed on serum samples obtained from 35 acne vulgaris patients before and after three months of isotretinoin treatment. PON1 activity, total oxidant status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI) and some routine biochemical parameters were monitored. Results: Dramatically decreased PON1 activity (p < 0.001), increased TOS level and OSI value (p < 0.001 and p < 0.001; respectively) as well as slightly diminished TAC level were noted in posttreatment stage. Moreover significant increases were observed in lactate dehydrogenase and gamma glutamyl transpeptidase activities and levels of total cholesterol, low density lipoprotein cholesterol, very low density lipoprotein cholesterol, triglycerides, low density lipoprotein cholesterol/high density lipoprotein cholesterol ratio respectively (p < 0.05, p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001 and p < 0.001) while marked decrease was seen in high density lipoprotein cholesterol (p < 0.01). Conclusion: This study revealed that decreased PON1 activity and increased oxidative stress may have a crucial role in the pathogenesis of isotretinoin’s side effects. Further studies on a large number of patients are needed to verify these results.

Immunoregulatory effects of isotretinoin in patients with acne

In vitro studies have shown that retinoids influence T-cell differentiation. To study the effect of isotretinoin on T-cell differentiation markers in patients with acne. A total of 37 patients with acne vulgaris (25 female, 12 male, age 19.6 ± 3.7 years) and 30 age- and sex-matched healthy controls (19 female, 11 male, age 20.5 ± 4.4 years) were included in the study. Screening for biochemical parameters in serum samples were done just before initiation (pretreatment) and after 3 months of isotretinoin treatment (post-treatment) in the acne group. Baseline levels of tumour necrosis factor (TNF)-α (P<0.0001), interleukin (IL)-4 (P<0.0001), IL-17 (P<0.0001) and interferon (IFN)-γ (P=0.002) were significantly higher in the acne group compared with the control group. TNF-α (P<0.0001), IL-4 (P<0.0001), IL-17 (P<0.0001) and IFN-γ (P<0.0001) levels decreased after isotretinoin treatment. TNF-α and IL-4 values after isotretinoin treatment were similar to those of the control group. However, levels of IL-17 (P<0.0001) after isotretinoin treatment were higher than those of the control group, despite a significant decline after treatment. Levels of IFN-γ (P<0.0001) after isotretinoin treatment were lower than those of the control group. This study shows that isotretinoin treatment significantly decreases TNF, IL-4, IL-17 and IFN-γ levels in patients with acne. We failed to show that isotretinoin redirects naive T helper (Th) differentiation preferentially towards the Th2 cell lineage.

Isotretinoin does not induce insulin resistance in patients with acne

Isotretinoin treatment causes hypertriglyceridaemia. Insulin resistance is also associated with hypertriglyceridaemia. It is not known if isotretinoin is related to insulin resistance. To test this hypothesis, we measured insulin resistance in 48 patients with acne vulgaris (AV) before and after 3 months of isotretinoin treatment. In total, 48 patients with AV who attended the dermatology outpatient clinic at Kecioren Research and Training Hospital were included. Screening for biochemical parameters was performed just before the start of treatment (pretreatment) and after 4 months of isotretinoin therapy (post-treatment). The parameters measured were insulin, C peptide, fasting blood glucose, aspartate and alanine aminotransferases (AST, ALT), total cholesterol (TC), triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL-C) and very low-density lipoprotein cholesterol. Insulin resistance was measured using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) method. Compared with initial values, AST, ALT, TC, LDL-C and triglyceride levels were significantly increased (P < 0.01, < 0.05, < 0.01, < 0.05 and < 0.01, respectively), but there was no significant change in fasting blood glucose, insulin, C-peptide levels or HOMA-IR. Three months of isotretinoin treatment did not change insulin sensitivity in patients with AV. Further studies with insulin resistance models may even reveal an improvement in insulin resistance, as experimental animal studies have previously shown.

THERAPEUTIC HOTLINE: Does isotretinoin have effect on vitamin D physiology and bone metabolism in acne patients?

Isotretinoin is an effective therapy for severe nodulocystic acne. Several experimental studies suggest that it may have an effect on vitamin D physiology. In the present study, the authors aimed to investigate the effect of isotretinoin treatment on the metabolism of vitamin D in acne patients. A prospective analysis of 50 consecutive acne patients who were treated with isotretinoin for 3 months was done. Before and after 3 months of treatment, 25 hydroxy vitamin D, 1,25 dihydroxy vitamin D, and bone alkaline phosphatase, calcium, phosphate, and parathormone levels were measured. The 25 hydroxy vitamin D and serum calcium levels decreased significantly (p < 0.0001, p < 0.05, respectively), whereas 1,25 dihydroxy vitamin D, parathormone, and bone alkaline phosphatase levels increased significantly after 3 months of isotretinoin treatment (p < 0.005, p < 0.005, p < 0.0001, respectively). Aspartate aminotransferase, total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels also increased significantly after isotretinoin treatment. This prospective clinical study showed that isotretinoin has an effect on vitamin D metabolism. Further clinical studies with longer periods of follow-up are needed to understand the effect of isotretinoin on vitamin D and bone metabolism.

Does isotretinoin therapy have any effects on electrocardiography, heart rate and blood pressure?

Background: Isotretinoin therapy is associated with numerous adverse effects of various systems. Although some cases have been reported, cardiac side effects are rare following isotretinoin treatment. Objective: To investigate the effects of isotretinoin on the cardiovascular system. Methods: Seventy patients with acne vulgaris were enrolled in the study. The patients were treated with a dose of 0.5–1.0 mg/kg per day of isotretinoin. Screening for biochemical and hematologic parameters, heart rate, blood pressure and electrocardiographic parameters were done before treatment and after 3 months of isotretinoin treatment. Results: Heart rate, systolic/diastolic tension and electrocardiographic parameters (P-wave duration and QTc duration) were not statistically different before compared with after treatment. Conclusion: As far as we know, there is no study researching the effect of isotretinoin on P- and QT-wave measurements in the literature. We found that isotretinoin did not affect P- and QT-wave measurement. Further studies with longer periods of follow-up are needed to understand the effect of isotretinoin on the cardiovascular system.

Isotretinoin Influences Pituitary Hormone Levels in Acne Patients

Besides suppressing sebum production, the exact mechanism of action of isotretinoin in acne vulgaris is not known. Several hormones have been linked to the pathogenesis of acne. In this study, we investigated the effects of isotretinoin on the pituitary-adrenal axis, whose activity may be increased in acne. Various hormone systems were evaluated before and after 3 months of isotretinoin treatment in 47 acne patients. Free triiodothyronine (T3), thyroid-stimulating hormone and thyroid-stimulating hormone receptor antibody levels decreased significantly during isotretinoin treatment (p < 0.001, p < 0.02 and p < 0.02, respectively), as did those of luteinising hormone, prolactin and total testosterone (p < 0.005), as well as morning cortisol and adrenocorticotropic hormone (p < 0.005 and p < 0.05, respectively). We conclude that isotretinoin causes mild suppression of pituitary hormone levels, which may be beneficial for tackling the pathogenesis of acne.

Type I collagen N-telopeptide variation in adolescents receiving oral isotretinoin for severe acne.

The prolonged use of retinoids has been reported to be associated with changes of bone biochemical markers and toxic skeletal effects. Among collagen markers, type I collagen N-telopeptide (NTx) is present in all tissues that contain type I collagen, mostly in bone and in cutaneous tissue. It is a reliable indicator of bone resorption in metabolic bone disease, but has not previously been investigated in dermatological diseases during retinoid therapy. Isotretinoin, a synthetic 13-cis-retinoic acid, is highly effective in the treatment of severe acne vulgaris. We evaluated the effect of low-dose short-term oral isotretinoin treatment on bone remodeling markers in 10 adolescents (mean age 17.8 years) affected by severe acne. We measured urinary NTx as a marker of bone resorption, alkaline phosphatase (ALP) and osteocalcin (OC) as markers of bone formation, parathyroid hormone (PTH) and metabolites of vitamin D (25OH-D3 and 1,25(OH)2D3). Clinical and laboratory tests were performed before and after three months of isotretinoin treatment at the dosage of 0.5 mg/kg/day. All patients showed a good clinical response to the treatment (7/10 marked improvement, 3/10 mild improvement). No changes were detected in serum PTH, 25OH-D3, 1,25(OH)2D3, OC and ALP, while urinary NTx concentrations were significantly reduced (p < 0.05). In conclusion, the lack of change in PTH, OC, ALP and vitamin D metabolites and the absence of increase of NTx suggest no bone effect of the isotretinoin treatment. The decrease of urinary NTx could be due to the effect of isotretinoin on the cutaneous component of type I collagen. Severe acne in the active inflammatory phase could change the levels of this marker. Thus, short-term low-dose oral isotretinoin is an effective and safe treatment for severe acne.

Effect of oral isotretinoin treatment on skin androgen receptor levels in male acneic patients.

An oral daily dose (mean +/- SD, 0.75 +/- 0.05 mg/kg) of isotretinoin was administered for 3 months to six male patients with acne (scores of 4 and 5 according to Rosenfield). The therapy resulted in complete resolution of acne in four patients and improved acne significantly (score 1) in two patients. In accordance with recent findings, no change in serum testosterone and significant decreases in 5 alpha-dihydrotestosterone, 5 alpha-androstane-3 alpha,17 beta-diol glucosiduronate, and androsterone glucosiduronate levels were observed after treatment. Androgen receptor status was investigated in back skin biopsies obtained in acne areas before and after 3 months of isotretinoin treatment. The treatment did not modify the binding affinity constant of skin androgen receptor (0.44 vs. 0.32 nmol/L), but it did induce a 2.6-fold decrease in its binding capacity constant (62 vs. 24 fmol/mg cytosolic protein), as assessed by Scatchard plot and confirmed immunologically by Western blot analysis. These data clearly showed that skin androgen receptor was sensitive to oral isotretinoin administration in acneic patients. The decrease in skin androgen receptor levels (this study) and the recently reported suppression of skin 5 alpha-dihydrotestosterone production by isotretinoin treatment appeared consistent with the involvement of androgen receptor and 5 alpha-dihydrotestosterone in the pathogenesis of acne. Indeed, sebum production is under androgen control, and an abnormal response of the pilosebaceous unit to androgens appears to be implicated in the pathogenesis of acne. These observations were consistent with the absence of sebum in complete androgen-insensitive patients and normal sebum production in male pseudohermaphrodites.