Drareg
Member
- Joined
- Feb 18, 2016
- Messages
- 4,772
I don’t have hair loss problems but I do find the expression of hair and hair color in different tissues very interesting.
I don’t know if FFA is spoken about much in male hair loss circles because it’s mainly a female problem, I stumbled upon it looking into the now world famous hydroxychloroquine because of COVID 19 instant death virus.
Below is from Wikipedia -Frontal fibrosing alopecia - Wikipedia
"Frontal fibrosing alopecia has been most often reported in post-menopausal women with higher levels of affluence and a negative smoking history. Autoimmune disease is found in 30% of patients"
"Although the pathogenesis of frontal fibrosing alopecia is poorly understood, autoimmune reaction and hormonal factors may play a role"
"Important diagnoses to consider include female pattern hair loss (FPHL), chronic telogen effluvium (CTE), and alopecia areata (AA). FPHL is a non-scarring progressive miniaturization of the hair follicle with one of three different characteristic patterns. CTE is an idiopathic disease causing increased hair shedding and bi-temporal recession, usually in middle aged women. AA is an autoimmune attack of hair follicles that usually causes hair to fall out in small round patches"
"Improvement or stabilization of the condition has been reported with topical and intralesional corticosteroids, antibiotics, hydroxychloroquine, topical and oral immunomodulators, tacrolimus, and most recently, 5α-reductase inhibitors. In one study, the use of antiandrogens (finasteride or dutasteride) was associated with improvement in 47% and stabilization in 53% of patients [13] Recently, successful treatment of facial papules in patients with frontal fibrosing alopecia was described with oral isotretinoin"
The below study is worth a read-
Frontal fibrosing alopecia: An update on the hypothesis of pathogenesis and treatment - ScienceDirect
"Frontal fibrosing alopecia (FFA) is a relatively new scarring alopecia that is considered a variant of lichen planopilaris (LPP) with no recognized promising treatments. In this study, we tried to clarify the underlying signaling pathwaysand their roles in the pathogenesis and progression of FFA. Because of several differences in clinical manifestations, response to treatments, and pathological findings, these two conditions could be differentiated from each other. Taking into account the already discussed signaling pathways and involved players such as T cells, mast cells, and sebaceous glands, different possible therapeutic options could be suggested. In addition to treatments supported by clinical evidence, such as 5 alpha-reductase inhibitors, topical calcineurin inhibitors, hydroxychloroquine, peroxisome proliferator-activated receptor gamma agonists, and oral retinoid agents, various other treatment strategies and drugs, such as phototherapy, Janus kinase inhibitors, dehydroepiandrosterone, sirolimus, cetirizine, and rituximab, could be suggested to mitigate disease progression. Of course, such lines of treatment need further evaluation in clinical trials"
"Inflammation around the hair follicles is suggested as the etiology of hair loss in primary scarring alopecia, but there is not enough detail about the pathogenesis of LPP and FFA"
"Unfortunately, currently available treatments are not very effective to stop hair loss, although the progression of the diseases can be slowed with 5 alpha-reductase inhibitors (5αRI; eg, dutasteride and finasteride), hydroxychloroquine (HCQ), and oral retinoid agents (MacDonald et al., 2012). Conversely, topical and systemic corticosteroids and immunosuppressive drugs, such as mycophenolate mofetil, do not halt the progression of FFA (Kossard et al., 1997, Tosti et al., 2005), which may be due to the difference in predominant immune responses and the involvement of different immune pathways in these diseases. Moreover, the differences in the targeted hair types (ie, vellus, intermediate, and terminal) need more discussion."
"Although eyebrow loss was reported in both men and women, women may be affected more frequently than men with FFA (Bolduc et al., 2016). Moreover, eyebrow loss as the initial clinical presentation was associated with mild forms of FFA (Bolduc et al., 2016). Interestingly, involvement of the eyebrows precedes a frontal recession without any sign of clinical inflammation"
"There are major differences related to the response to treatment by patients with FFA and LPP. LPP responds well to topical or intralesional injection of corticosteroid agents as well as some immunosuppressive therapies, but these treatments were not found effective for FFA (Lajevardi et al., 2015). On the other hand, there is growing evidence that FFA progression can be halted with 5αRI (eg, dutasteride and finasteride), oral retinoid agents, and peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists (Chiang et al., 2010, Pedrosa et al., 2017, Pirmez et al., 2017, Rakowska et al., 2017, Samrao et al., 2010, Vano-Galvan et al., 2014). Of note, some treatments, such as HCQ, appear effective not only for FFA, but also in decreasing symptoms and signs of LPP"
"There is a growing body of evidence that fibrotic pathways and specifically epithelial-to-mesenchymal transition (EMT) are deeply involved in FFA. EMT is a physiologic feature during embryogenesis and wound healing, but it also occurs during fibrotic diseases, malignant transformation of epithelial cells, and metastasis (Nieto et al., 2016). During EMT, epithelial cells gradually represent fibroblast-like morphology (such as vimentin and fibronectinupregulation) as a result of E-cadherin suppression via E-box binding factors, such as SNAI1, SNAI2, and TWIST"
"In addition to PPAR-γ agonists, which have documented efficacy in hampering EMT (Burgess et al., 2005, Zafiriou et al., 2005), retinoid agents are well known to have proven inhibitory effects against fibrosis pathways and can act as an agonist of PPAR-γ (Rankin et al., 2013). Furthermore, new evidence supports the inhibitory effect of 5αRIs in the TGF-β1-fibrosis pathway for the treatment of various types of alopecia (Inui and Itami, 2011, Yoo et al., 2006). Also, there is evidence for the role of androgens, especially dehydroepiandrosterone (DHEA), in suppressing TGF-β1 and fibrosis"
"At first glance, considering the high prevalence of FFA in postmenopausal women, estrogen deficiency could be considered as a triggering factor of FFA initiation. Estrogen has many known effects on different parts of the immune system, and it has regulatory effects on the function and number of neutrophils and macrophages (Hsieh et al., 2009, Kovats, 2015). Moreover, high levels of estrogen (eg, during pregnancy) can shift the immune response from Th1 to Th2 cells"
"Simultaneously, estrogen receptor-alpha (ERα)-mediated signaling upregulates the expression of FoxP3, programmed cell death protein 1, and CTLA-4. Thus, estrogen seems capable of promoting the expansion of Tregs, which are critical players in the downregulation of immune responses (Polanczyk et al., 2005). However, the serum levels of estrogen have been reported as normal in previous reports, and FFA has been reported in a man who received estrogen as part of neoadjuvant hormonal therapy for prostate cancer. These observations question the protective role of estrogen in FFA"
"The reported effectiveness of 5αRIs in FFA management can be justified with the microenvironmental estrogen deficiency theory. Aromatase is the responsible enzyme for the conversion of androgens (specifically testosterone) into estrogen, and it is found in many tissues including hair follicles. Both finasteride and dutasteride inhibit the conversion of testosterone into dihydrotestosterone, leading to higher levels of testosterone in the scalp. Subsequently, this accumulated testosterone is converted to estrogen by activated aromatase. Consequently, 5αRIs increase the estrogen level in the scalp microenvironment, which could implement many anti-inflammatory effects. However, considering the high prevalence of AGA in patients with FFA and the well-known effects of 5αRIs in the treatment of AGA. The efficacy of 5αRIs in FFA patients could probably conditioned by its effect on improving AGA rather than FFA"
"Second, a new growing concept is built on the basis of the low androgen level theory, which has been discussed very recently in the literature. Ranasinghe et al. (2017) reported that androgen deficiency (especially DHEA and DHEA sulphate) has been identified in many patients with FFA. DHEA and DHEA sulphate are the most abundant circulating steroid hormones in humans. Their production in women reaches the highest levels between the age of 25 and 30 years and starts decreasing at age 60 years, with only 10% to 20% of peak levels"
"In view of the biochemical effects, DHEA exhibits affinity to the androgen receptor (AR) and estrogen receptors (ERs) with a preference for ER-β (Chen et al., 2005)."
"Surprisingly, depending on the circulating testosterone and dihydrotestosterone levels, DHEA has been shown to behave as a partial agonistof AR, and therefore probably has an anti-androgen effect. On the other hand, DHEA is a full agonist of ERβ with similar or slightly greater effect than estradiol. As such, DHEA has been proposed to be an important and potentially major endogenous estrogen in the body (Webb et al., 2006). Thus, considering the anti-inflammatory, anti-fibrosis, anti-androgen, and estrogen-like effects, DHEA can be a potentially effective treatment for FFA. Of note, despite these theories on the role of DHEA, since FFA is occurs in postmenopausal women in > 90% of cases, the significantly lower serum levels of DHEA in the study by Ranasinghe et al. (2017) could be due to the higher mean age of the patients with FFA, and not necessarily a triggering factor for FFA"
"Lastly, the association of FFA with hypothyroidism and the effect of thyroid hormones on K15, CD200, and deiodinase 2 in cultured human K15-GFP + cells suggest a potential role of thyroid hormones in maintaining the stem cell niche/bulge immune privilege in FFA"
The microenvironmental estrogen theory is a magic just so story on top of another just so story, it’s still an instructive study, the diodinase enzymes have more involvement in baldness and could be the key IMO.
Below is the study on the guy receiving estrogen therapy who had FFA hair loss ,I don’t see the mention to estrogen or prostate cancer in this study ?
Frontal Fibrosing Alopecia in a Male Presenting with Sideburn Loss
I don’t know if FFA is spoken about much in male hair loss circles because it’s mainly a female problem, I stumbled upon it looking into the now world famous hydroxychloroquine because of COVID 19 instant death virus.
Below is from Wikipedia -Frontal fibrosing alopecia - Wikipedia
"Frontal fibrosing alopecia has been most often reported in post-menopausal women with higher levels of affluence and a negative smoking history. Autoimmune disease is found in 30% of patients"
"Although the pathogenesis of frontal fibrosing alopecia is poorly understood, autoimmune reaction and hormonal factors may play a role"
"Important diagnoses to consider include female pattern hair loss (FPHL), chronic telogen effluvium (CTE), and alopecia areata (AA). FPHL is a non-scarring progressive miniaturization of the hair follicle with one of three different characteristic patterns. CTE is an idiopathic disease causing increased hair shedding and bi-temporal recession, usually in middle aged women. AA is an autoimmune attack of hair follicles that usually causes hair to fall out in small round patches"
"Improvement or stabilization of the condition has been reported with topical and intralesional corticosteroids, antibiotics, hydroxychloroquine, topical and oral immunomodulators, tacrolimus, and most recently, 5α-reductase inhibitors. In one study, the use of antiandrogens (finasteride or dutasteride) was associated with improvement in 47% and stabilization in 53% of patients [13] Recently, successful treatment of facial papules in patients with frontal fibrosing alopecia was described with oral isotretinoin"
The below study is worth a read-
Frontal fibrosing alopecia: An update on the hypothesis of pathogenesis and treatment - ScienceDirect
"Frontal fibrosing alopecia (FFA) is a relatively new scarring alopecia that is considered a variant of lichen planopilaris (LPP) with no recognized promising treatments. In this study, we tried to clarify the underlying signaling pathwaysand their roles in the pathogenesis and progression of FFA. Because of several differences in clinical manifestations, response to treatments, and pathological findings, these two conditions could be differentiated from each other. Taking into account the already discussed signaling pathways and involved players such as T cells, mast cells, and sebaceous glands, different possible therapeutic options could be suggested. In addition to treatments supported by clinical evidence, such as 5 alpha-reductase inhibitors, topical calcineurin inhibitors, hydroxychloroquine, peroxisome proliferator-activated receptor gamma agonists, and oral retinoid agents, various other treatment strategies and drugs, such as phototherapy, Janus kinase inhibitors, dehydroepiandrosterone, sirolimus, cetirizine, and rituximab, could be suggested to mitigate disease progression. Of course, such lines of treatment need further evaluation in clinical trials"
"Inflammation around the hair follicles is suggested as the etiology of hair loss in primary scarring alopecia, but there is not enough detail about the pathogenesis of LPP and FFA"
"Unfortunately, currently available treatments are not very effective to stop hair loss, although the progression of the diseases can be slowed with 5 alpha-reductase inhibitors (5αRI; eg, dutasteride and finasteride), hydroxychloroquine (HCQ), and oral retinoid agents (MacDonald et al., 2012). Conversely, topical and systemic corticosteroids and immunosuppressive drugs, such as mycophenolate mofetil, do not halt the progression of FFA (Kossard et al., 1997, Tosti et al., 2005), which may be due to the difference in predominant immune responses and the involvement of different immune pathways in these diseases. Moreover, the differences in the targeted hair types (ie, vellus, intermediate, and terminal) need more discussion."
"Although eyebrow loss was reported in both men and women, women may be affected more frequently than men with FFA (Bolduc et al., 2016). Moreover, eyebrow loss as the initial clinical presentation was associated with mild forms of FFA (Bolduc et al., 2016). Interestingly, involvement of the eyebrows precedes a frontal recession without any sign of clinical inflammation"
"There are major differences related to the response to treatment by patients with FFA and LPP. LPP responds well to topical or intralesional injection of corticosteroid agents as well as some immunosuppressive therapies, but these treatments were not found effective for FFA (Lajevardi et al., 2015). On the other hand, there is growing evidence that FFA progression can be halted with 5αRI (eg, dutasteride and finasteride), oral retinoid agents, and peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists (Chiang et al., 2010, Pedrosa et al., 2017, Pirmez et al., 2017, Rakowska et al., 2017, Samrao et al., 2010, Vano-Galvan et al., 2014). Of note, some treatments, such as HCQ, appear effective not only for FFA, but also in decreasing symptoms and signs of LPP"
"There is a growing body of evidence that fibrotic pathways and specifically epithelial-to-mesenchymal transition (EMT) are deeply involved in FFA. EMT is a physiologic feature during embryogenesis and wound healing, but it also occurs during fibrotic diseases, malignant transformation of epithelial cells, and metastasis (Nieto et al., 2016). During EMT, epithelial cells gradually represent fibroblast-like morphology (such as vimentin and fibronectinupregulation) as a result of E-cadherin suppression via E-box binding factors, such as SNAI1, SNAI2, and TWIST"
"In addition to PPAR-γ agonists, which have documented efficacy in hampering EMT (Burgess et al., 2005, Zafiriou et al., 2005), retinoid agents are well known to have proven inhibitory effects against fibrosis pathways and can act as an agonist of PPAR-γ (Rankin et al., 2013). Furthermore, new evidence supports the inhibitory effect of 5αRIs in the TGF-β1-fibrosis pathway for the treatment of various types of alopecia (Inui and Itami, 2011, Yoo et al., 2006). Also, there is evidence for the role of androgens, especially dehydroepiandrosterone (DHEA), in suppressing TGF-β1 and fibrosis"
"At first glance, considering the high prevalence of FFA in postmenopausal women, estrogen deficiency could be considered as a triggering factor of FFA initiation. Estrogen has many known effects on different parts of the immune system, and it has regulatory effects on the function and number of neutrophils and macrophages (Hsieh et al., 2009, Kovats, 2015). Moreover, high levels of estrogen (eg, during pregnancy) can shift the immune response from Th1 to Th2 cells"
"Simultaneously, estrogen receptor-alpha (ERα)-mediated signaling upregulates the expression of FoxP3, programmed cell death protein 1, and CTLA-4. Thus, estrogen seems capable of promoting the expansion of Tregs, which are critical players in the downregulation of immune responses (Polanczyk et al., 2005). However, the serum levels of estrogen have been reported as normal in previous reports, and FFA has been reported in a man who received estrogen as part of neoadjuvant hormonal therapy for prostate cancer. These observations question the protective role of estrogen in FFA"
"The reported effectiveness of 5αRIs in FFA management can be justified with the microenvironmental estrogen deficiency theory. Aromatase is the responsible enzyme for the conversion of androgens (specifically testosterone) into estrogen, and it is found in many tissues including hair follicles. Both finasteride and dutasteride inhibit the conversion of testosterone into dihydrotestosterone, leading to higher levels of testosterone in the scalp. Subsequently, this accumulated testosterone is converted to estrogen by activated aromatase. Consequently, 5αRIs increase the estrogen level in the scalp microenvironment, which could implement many anti-inflammatory effects. However, considering the high prevalence of AGA in patients with FFA and the well-known effects of 5αRIs in the treatment of AGA. The efficacy of 5αRIs in FFA patients could probably conditioned by its effect on improving AGA rather than FFA"
"Second, a new growing concept is built on the basis of the low androgen level theory, which has been discussed very recently in the literature. Ranasinghe et al. (2017) reported that androgen deficiency (especially DHEA and DHEA sulphate) has been identified in many patients with FFA. DHEA and DHEA sulphate are the most abundant circulating steroid hormones in humans. Their production in women reaches the highest levels between the age of 25 and 30 years and starts decreasing at age 60 years, with only 10% to 20% of peak levels"
"In view of the biochemical effects, DHEA exhibits affinity to the androgen receptor (AR) and estrogen receptors (ERs) with a preference for ER-β (Chen et al., 2005)."
"Surprisingly, depending on the circulating testosterone and dihydrotestosterone levels, DHEA has been shown to behave as a partial agonistof AR, and therefore probably has an anti-androgen effect. On the other hand, DHEA is a full agonist of ERβ with similar or slightly greater effect than estradiol. As such, DHEA has been proposed to be an important and potentially major endogenous estrogen in the body (Webb et al., 2006). Thus, considering the anti-inflammatory, anti-fibrosis, anti-androgen, and estrogen-like effects, DHEA can be a potentially effective treatment for FFA. Of note, despite these theories on the role of DHEA, since FFA is occurs in postmenopausal women in > 90% of cases, the significantly lower serum levels of DHEA in the study by Ranasinghe et al. (2017) could be due to the higher mean age of the patients with FFA, and not necessarily a triggering factor for FFA"
"Lastly, the association of FFA with hypothyroidism and the effect of thyroid hormones on K15, CD200, and deiodinase 2 in cultured human K15-GFP + cells suggest a potential role of thyroid hormones in maintaining the stem cell niche/bulge immune privilege in FFA"
The microenvironmental estrogen theory is a magic just so story on top of another just so story, it’s still an instructive study, the diodinase enzymes have more involvement in baldness and could be the key IMO.
Below is the study on the guy receiving estrogen therapy who had FFA hair loss ,I don’t see the mention to estrogen or prostate cancer in this study ?
Frontal Fibrosing Alopecia in a Male Presenting with Sideburn Loss
