infrainfra
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long story short
Isotretinoin undergoes isomerization to all-trans-retinoic acid. so just tretinoin.
retinoic acid binds to retinoic acid receptors and RXR (retinoid x receptors)
this directly changes the transcription of genes controlling cartilage maturation
look at this :
„Twenty 3-week-old male rats were randomly divided into a control group and an experimental group (n = 10). The experimental rats were treated by gavage with high-dose ATRA for 10 days. After this period, the experimental rats exhibited a lower body weight and shorter nasal-tail and radial tibial length than the controls. CYP26B1 enzyme activity in the liver was elevated, and histopathological staining revealed a narrowed cartilaginous epiphyseal plate, a sparse medullary cavity of trabecular bone, fewer trabecular bones, and advanced bone marrow mineralization. The circulating GH, IGF-I, and IGFBP3 levels decreased. The authors concluded that high-dose ATRA intake over a brief period reduces GH, IGF-I, and IGFBP3 levels, affects cartilage and bone homeostasis, and inhibits bone growth in developing animals ”
ATRA = all trans retinoic acid*
There is more. Study on humans :
„Karadag et al. studied the effect of isotretinoin on the GH-IGF-I axis in 47 patients (15–40 years) with acne. The therapy was initiated at a dose of 0.5–0.75 mg/kg/day and adjusted to 0.88 mg/kg/day as a maintenance dosage after 1 month. After 3 months of treatment, the IGF-I and IGFBP3 levels significantly decreased, while the mean basal GH levels did not change.”
„In another study of the same group of researchers including 105 patients with acne (14–42 years), the participants were divided into three groups based on the isotretinoin dose: 0.5–1.0 mg/kg/day (high dose—group 1), 0.2–0.5 mg/kg/day (low dose—group 2), and an intermittent 0.5–1.0 mg/kg/day only one week per month (intermittent dose—group 3). After 3 months of therapy, the isotretinoin significantly reduced the IGF-I and random GH levels in groups 1 and 2, and these effects were more pronounced in the high-dose group. The IGFBP3 levels were significantly reduced in all three groups, and the weakest effect was seen in the intermittent-dose group . The total testosterone and cortisol levels decreased, and the sex hormone-binding globulin (SHBG) levels increased significantly in the three groups after therapy.”
look at this : „The total testosterone and cortisol levels decreased, and the sex hormone-binding globulin (SHBG) levels increased significantly”
SO IT ALSO FUCKS WITH OTHER HORMONES.
take a look at that for a little summary
doesnt stop here. take a look at this
Now recently a clinical case of a boy suggests that elevated retinoic acid concentrations accelerate bone and dental maturation in humans.
„The patient was a 10-year-old prepubertal boy with retinal scarring, photophobia, autism spectrum disease, markedly advanced bone age, and accelerated dental development. He was born full term after an uncomplicated pregnancy and delivery, with a birth weight of 2.98 kg [−1.3 standard deviation score (SDS)] and birth length of 46 cm (−2.3 SDS). At the physical exam, he had pubic hair Tanner II, a testicular size of 3–4 mL bilaterally, and no gynecomastia. He presented with low serum vitamin A and elevated total and 13-cis-retinoc acid concentrations and a 3-year advance in bone age, which was advanced in relation to the chronological age without elevated estrogen levels. This syndrome was associated with a deletion on chromosome 10q23, which included the genes of the major retinoic acid-metabolizing enzymes”
okay enough of in vivo studies
i will just type out the mechanisms it fucks your puberty so you can understand it
It pushes chondros into hypertrophy faster so just less bone lengthening.
it also supresses chondrocyte proliferation.
The growth plate only has a finite number of proliferative chondrocytes. Anything that causes these cells to stop dividing or disappear faster will just accelerate growth plate aging. this is also called senescence
it increases mineralization and ossification so cartilage becomes bone faster. so growth potential is lost sooner.
there is more mechanisms in which isotret (accutane) will fuck you up. IDK AND IDC this is enough not to use it.
is there any solution? yes - topical anti androgens with low systemic absorption for the same use-case of isotret (acne)
Stupid chatgpt
Isotretinoin undergoes isomerization to all-trans-retinoic acid. so just tretinoin.
retinoic acid binds to retinoic acid receptors and RXR (retinoid x receptors)
this directly changes the transcription of genes controlling cartilage maturation
look at this :
„Twenty 3-week-old male rats were randomly divided into a control group and an experimental group (n = 10). The experimental rats were treated by gavage with high-dose ATRA for 10 days. After this period, the experimental rats exhibited a lower body weight and shorter nasal-tail and radial tibial length than the controls. CYP26B1 enzyme activity in the liver was elevated, and histopathological staining revealed a narrowed cartilaginous epiphyseal plate, a sparse medullary cavity of trabecular bone, fewer trabecular bones, and advanced bone marrow mineralization. The circulating GH, IGF-I, and IGFBP3 levels decreased. The authors concluded that high-dose ATRA intake over a brief period reduces GH, IGF-I, and IGFBP3 levels, affects cartilage and bone homeostasis, and inhibits bone growth in developing animals ”
ATRA = all trans retinoic acid*
There is more. Study on humans :
„Karadag et al. studied the effect of isotretinoin on the GH-IGF-I axis in 47 patients (15–40 years) with acne. The therapy was initiated at a dose of 0.5–0.75 mg/kg/day and adjusted to 0.88 mg/kg/day as a maintenance dosage after 1 month. After 3 months of treatment, the IGF-I and IGFBP3 levels significantly decreased, while the mean basal GH levels did not change.”
„In another study of the same group of researchers including 105 patients with acne (14–42 years), the participants were divided into three groups based on the isotretinoin dose: 0.5–1.0 mg/kg/day (high dose—group 1), 0.2–0.5 mg/kg/day (low dose—group 2), and an intermittent 0.5–1.0 mg/kg/day only one week per month (intermittent dose—group 3). After 3 months of therapy, the isotretinoin significantly reduced the IGF-I and random GH levels in groups 1 and 2, and these effects were more pronounced in the high-dose group. The IGFBP3 levels were significantly reduced in all three groups, and the weakest effect was seen in the intermittent-dose group . The total testosterone and cortisol levels decreased, and the sex hormone-binding globulin (SHBG) levels increased significantly in the three groups after therapy.”
look at this : „The total testosterone and cortisol levels decreased, and the sex hormone-binding globulin (SHBG) levels increased significantly”
SO IT ALSO FUCKS WITH OTHER HORMONES.
take a look at that for a little summary
doesnt stop here. take a look at this
Now recently a clinical case of a boy suggests that elevated retinoic acid concentrations accelerate bone and dental maturation in humans.
„The patient was a 10-year-old prepubertal boy with retinal scarring, photophobia, autism spectrum disease, markedly advanced bone age, and accelerated dental development. He was born full term after an uncomplicated pregnancy and delivery, with a birth weight of 2.98 kg [−1.3 standard deviation score (SDS)] and birth length of 46 cm (−2.3 SDS). At the physical exam, he had pubic hair Tanner II, a testicular size of 3–4 mL bilaterally, and no gynecomastia. He presented with low serum vitamin A and elevated total and 13-cis-retinoc acid concentrations and a 3-year advance in bone age, which was advanced in relation to the chronological age without elevated estrogen levels. This syndrome was associated with a deletion on chromosome 10q23, which included the genes of the major retinoic acid-metabolizing enzymes”
okay enough of in vivo studies
i will just type out the mechanisms it fucks your puberty so you can understand it
It pushes chondros into hypertrophy faster so just less bone lengthening.
it also supresses chondrocyte proliferation.
The growth plate only has a finite number of proliferative chondrocytes. Anything that causes these cells to stop dividing or disappear faster will just accelerate growth plate aging. this is also called senescence
it increases mineralization and ossification so cartilage becomes bone faster. so growth potential is lost sooner.
there is more mechanisms in which isotret (accutane) will fuck you up. IDK AND IDC this is enough not to use it.
is there any solution? yes - topical anti androgens with low systemic absorption for the same use-case of isotret (acne)
Stupid chatgpt
