Captain Hook
Established Member
- Reaction score
- 44
Patient Information and History:
I am a 20-year-old male, 186 cm, 73 kg, Mediterranean descent, moderate drinker (7-21 units of ethanol per week), occasional non-habitual smoker (1-5 packs per year spread out throughout the year) and board certified pharmacy technician.
Supplements:
Daily: Centrum Men’s Multivitamin, Nature’s Own Triple Concentrated Fish Oil, Vitamin D3 1000 IU as cholecalciferol 25 mcg, Biotin 300-5000 mcg
3-5x per week: AllMax Nutrition Quickmass (contains 3.86 g creatine per serving)
PRN: choline bitartrate 100mg, Coenzyme Q10 100mg, No-Doz Plus, Vivarin, ephedrine, 2mg Nicorette gum, melatonin 1-10mg
5-6 months per year @ 3x per week: BSN N.O. Xplode pre-workout supplement (contains 2.5 g creatine per serving), Acetyl-L-Carnitine or L-Carnitine 500mg
Hair products:
-Silicone-free shampoo and conditioner (when not using Nizoral)
-Various styling products (mostly wax, paste or mousse)
There are known incidences of androgenic alopecia on my paternal side of the family, with my father having a Norwood grade I hairline at 62 years of age and my father’s brother being Norwood grade VII at age 55 with progression unknown. Only one incidence of advanced androgenic alopecia on my maternal side of the family, my maternal grandfather was at Norwood grade III until his early 40s and then progressed fully to Norwood grade VII shortly afterwards, my maternal grandfather did have type II diabetes but was otherwise in good health. My mother’s brothers progressed to Norwood grade II to III late in life, around age 40-50.
Treatment timeline:
(Studies can be found on Google by copying and pasting the study IDs I've mentioned)
I’ve been experiencing mild hair loss, first noticed at 19 years of age around April 2014, seeing slightly more hair on my hands in the shower after applying shampoo and conditioner (thankfully not in clumps but rather single strands).
Hair loss slowly worsened over the course of the year, especially so after my 20th birthday (September of 2014). I initially presented to my dermatologist with seborrhoeic dermatitis in early November 2014 (which is also when I began lurking on this forum) and was prescribed ciclopirox olamine 1.5% w/w shampoo in the form of Stieprox, after several months no regrowth was noticed, only worsening of hair loss.
I experienced a relapse of seborrhoeic dermatitis in mid-March 2015 and was treated with ketoconazole 2% w/w shampoo in the form of Nizoral with good success and there has been no further relapse of seborrhoeic dermatitis due to once a week prophylactic antifungal therapy with either Nizoral or Stieprox, with Stieprox being used more often due to its refreshing scent. Hair loss continued to worsen, albeit slowly, noticing hairs on my pillow at this point, similar to the hair I found on my hands in the shower, the hairs present on my pillow were also strands and not clumps.
To rule out any other possible causes of hair loss I requested that my GP perform several blood tests as follows:
Comprehensive metabolic panel with lipid profile, complete blood cell count, thyroid function test panel, iron studies, serum zinc, serum magnesium and comprehensive male hormone panel (I'm at uni now and will update the exact values for this panel when I get home as I left the envelope with the test results back home). All came back within their normal reference ranges save for the serum zinc test which actually came back slightly higher than normal, but not high enough to interfere with copper levels (which would’ve showed up as an abnormality in the iron studies since copper is essential for iron metabolism)
I visited my dermatologist once again during mid July 2015 to assess the degree of hair loss, dermatologist’s opinion as follows: androgenic alopecia unlikely but is unable to make a definitive diagnosis at this point due to the patient’s young age. After performing a pull test, examining the scalp and taking photos and measurements of the hairline the dermatologist concluded that my hair loss is not advanced enough to be graded on the Hamilton-Norwood scale, with the dermatologist specifically stating that my hairline hasn’t receded enough to look like Norwood grade I. (I understand there is no such thing as NW0 but I’m just going by what the dermatologist said verbatim)
I then asked ophthalmologist about the removal of one of my topical ophthalmic medications that I take daily (I have ocular hypertension), timolol maleate 0.5% to which he approves, since beta-blockers are sometimes an etiology of alopecia, after one month of cessation I noticed no improvement and continual worsening of hair loss. Interestingly enough, I also take latanoprost ophthalmic, which belongs to a class of medications called prostaglandin analogues, currently being studied as a future treatment for androgenic alopecia, with another drug in a similar class (prostamides), bimatoprost (Lumigan), being marketed as a treatment that lengthens eyelashes under the brand name Latisse. It may be of note that while timolol wasn’t causing my alopecia, at least not to the same degree as in this case report (http://www.reviewofophthalmology.com/content/d/features/i/1317/c/25352/ as you can see, even when this patient discontinued timolol and recovered, he still remained NW2-3, meaning that the cause of timolol related hair loss is androgen independent and henceforth male pattern alopecia alone is not grounds for ceasing timolol treatment) it definitely could’ve triggered the onset of androgenic alopecia, which is mentioned on the American Hair Loss Association’s website as a mechanism of drug induced hair loss: (http://www.americanhairloss.org/drug_induced_hair_loss/).
Around early August 2015, I notice my hair loss worsening especially around the temples. It is likely that I am now at the point where my hair loss can be assessed on the Hamilton-Norwood scale, since the hair loss is not marked and is in the early stages I’m likely classed as Norwood grade I. (I’m going by what the scale’s pictures look like, I may very well be NW2 but to be honest the scale isn’t exactly easy to interpret, do tell me what you guys think based on the attached photos, with an extra one of my crown that I took today after I got my haircut for clarification as I'm unsure if I'm actually thinning back there or not. I've also attached a photo of my hairline the way it was back in mid November 2014 before any major loss occured) Having ruled out all other possible causes of alopecia (medication induced, malnutrition, thyroid pathologies) I decide to undertake treatment for androgenic alopecia after a diagnosis of exclusion and noticing the characteristic ‘male pattern’ presentation of my hair loss. Treatment regimen with my reasoning for use as follows:
Ketoconazole:
Ketoconazole 2% shampoo treatment in the form of Nizoral 2% began on 16 August 2015 with twice weekly 5 minute applications while showering indefinitely to inhibit dihydrotestosterone (DHT) activity in the scalp via dual pharmacological mechanisms, acting as an antagonist at the androgen receptor so as to not allow DHT to bind to the receptor and hence cause damage to hair follicles and inhibition of the 17α-hydroxylase/CYP17A1 enzyme which prevents the synthesis of DHT. As well as antiandrogen activity, ketoconazole 2% shampoo has also proven to be more effective than minoxidil 2% in stimulating hair growth, providing an 18% increase in hair density versus minoxidil 2%’s 11%. (PMID: 9669136)
Many people have marked concern about ketoconazole 2% shampoo’s ability to be systemically absorbed, this is unfounded due to the fact that the package insert for Nizoral brand ketoconazole 2% shampoo clearly states that plasma concentrations of ketoconazole were not detectable after topical administration on the scalp while plasma levels were detected after topical administration on the entire body. Therefore systemic side effects should be non-existent if one is using ketoconazole 2% shampoo as intended.
Another concern regarding ketoconazole 2% shampoo is its frequency of use. Countless forum users have said ‘why do we only need to use it twice a week when other hair loss treatments we use every day”. The answer is simple; ketoconazole persists at therapeutic concentrations in the epidermal layers anywhere from 4-10 days, forgoing the need for daily use. (Kucers' The Use of Antibiotics Sixth Edition) This is due to its lipophilic nature and strong affinity for protein binding (read: keratin in the hair and scalp)
"Following a single application of ketoconazole shampoo, ketoconazole persists at therapeutic concentrations for 7 days in the epidermal layers. In addition, substantial pityrosporal inhibitory doses of ketoconazole were detected on the hair for several days after use of the shampoo, the mean level at 72 h was 11.6 µ mg."
(Pierard GE, Arrese JE, Pierard-Franchimont C, et al: Prolonged effects of antidandruff shampoos-time to recurrence of Malassezia ovalis colonization of skin. International Journal of Cosmetic Science. 1997;19:111-117.)
Again, if there’s any doubt in the treatment’s efficacy, look to the studies, where in one of them patients were only using the shampoo 2-4 times a week to achieve better results than daily 2% minoxidil use.
Lastly people seem to wonder if ketoconazole shampoo is ‘worth the hassle’. To be honest, I don’t see the inconvenience, we have to use shampoo in the shower anyway, and it only serves to conserve our normal shampoo if we use Nizoral twice a week. As well as controlling hair loss, I’ve personally had seborrhoeic dermatitis in the past and hence need to use an antifungal shampoo once a week indefinitely for prophylaxis to prevent a relapse of the condition, so for me using Nizoral is something I have to do regardless, so I figure it’s even easier to simply increase my usage to twice a week.
Spironolactone:
Spironolactone 5% topical cream treatment began on 30 August 2015 with twice daily applications indefinitely to inhibit DHT activity in the scalp via the same two mechanisms as ketoconazole albeit with much greater potency: androgen receptor antagonism and inhibition of the CYP17A1 enzyme as well as having three additional pharmacological mechanisms: progesterone receptor agonism which results in antigonadotropin effects, indirect estrogenic effects which increase the level of sex hormone binding globulin (SHBG binds to testosterone and hence lowers free T levels, therefore lowering the amount of free T converted to DHT) and the amount of testosterone converted to estradiol (meaning less T converted to DHT) and weak 5α-reductase inhibition (these last two lesser known mechanisms of spironolactone are supported via these studies: PMID: 7829618, PMID: 4033118, PMCID: PMC2923944)
I understand spironolactone can cause feminising effects when taken orally by men and hence most spironolactone studies are done only on women but while uncommon, the topical formulation has been proven in an older study on men and in a recent study on women to be effective for androgenic alopecia (alfatradiol is another antiandrogen that is effective for both men and women suffering from androgenic alopecia and it is clear that spironolactone is no different). It has also been proven that topical spironolactone is not absorbed systemically and hence has no endocrine systemic side effects. One of the studies showed even after applying 5% spironolactone cream to 55% of the patient’s body area, plasma canrenone levels (canrenone is the major metabolite of spironolactone) were undetectable during the 72 hours of treatment. Plasma levels of various hormones were measured both before and after application and also proved to be unaffected. (PMID: 3411088)
The specific topical spironolactone brand that I will be using is S5 Day Cream and will implement S5 Bedtime Cream after 2 months of use of the Day Cream. The reason being is to allow sufficient time to perform an allergy test and assess whether I tolerate the medication well (i.e. don't get a rash).
While some people are skeptical about the legitimacy of S5 cream and some even questioning its spironolactone content (a few people wondering if it even contains any spironolactone at all) all I have to say to that is that a decent trick to tell if spironolactone is present is its notorious odour. Being a drug that’s molecular structure contains a sulphur atom; it has a mercaptan-like odour, often described by many as a ‘rotten egg’ smell. I personally can confirm that S5 cream has this specific odour, although you can tell it’s been masked with limonene, resulting in a bit of a combination smell.
The vehicle used in S5 cream also comes under fire in various internet forums with many exclaiming ‘how do we know spironolactone is even absorbed at all’, this is also unfounded because the vehicle used for S5 (alcohol and triethanolamine) is the same as the vehicle used by compounding pharmacies who also make topical spironolactone formulations.
(Reference from this compounding pharmacy’s specific spironolactone formulation ID: US Pharm. 2012;37(12):43-44)
S5 Day Cream contains 1% caffeine in addition to 5% spironolactone; the addition of caffeine is thought to provide additional benefits for hair loss although further in vivo studies are needed to prove said benefits. (Evidence from in vitro studies showing stimulation of hair growth, suppression of androgen activity and 5α-reductase inhibition: PMID: 23075568, PMID: 24836650, PMID: 17214716)
S5 Bedtime cream contains no caffeine but instead includes 1% adenosine in addition to 5% spironolactone; the addition of adenosine is proven to provide benefits for hair loss with good evidence from studies done in humans, with results including thickening of hair density and one study even showing that topical adenosine in a 0.75% formulation was only slightly less effective than 5% minoxidil, with patients being more satisfied with the results from adenosine. (PMID: 24183218, PMID: 25925959)
It should be worth mentioning that while DHT is the pinnacle cause of androgenic alopecia, it is currently unknown whether other androgens have a pathological role. What we do know as of now is even those who are taking finasteride or even the potent dutasteride, some still inexplicably continue to lose hair and when a male with androgenic alopecia is castrated, said hair loss ceases to continue, this serves to suggest that other harmful androgens possibly have a lesser pathological role. With this in mind, androgen receptor antagonists such as ketoconazole and spironolactone offer peace of mind due to the fact that in addition to preventing DHT from binding to the androgen receptor, they also will prevent any other potentially harmful androgens from doing so as well.
Should hair loss not be controlled via the current treatment regimen, I will reassess after one year has elapsed and decide whether to add a topical 5α-reductase inhibitor such as alfatradiol. (References for effectiveness of topical alfatradiol: PMID: 7398983, PMID: 17451383, PMCID: PMC3412238)
I will not attempt treatment with minoxidil due to:
-Overall lack of long-term effectiveness as a hair growth stimulant, ending up being slightly better, equal or inferior compared to ketoconazole 2% and adenosine in concentrations of 0.75% and up depending on the concentration of minoxidil used.
-Lack of certain effectiveness since even Regaine/Rogaine’s website states that some minoxidil users only report maintenance or no effect at all (9/10 men kept or regrew hair was the exact statement, meaning it had no effect for 1/10 men and only some of the 9/10 experienced regrowth) and this recent study (PMID: 25112173) showing that the exact percentage of users that experience regrowth is only 40%. In addition, I’ve read Rogaine Foam has shown to provide regrowth in 85% of patients, so it seems results are equivocal.
-Absolute commitment to treatment as discontinuing minoxidil may cause rapid and irreversible loss of any newly grown hair whereas discontinuation of antiandrogens would simply allow DHT to slowly begin miniaturising hair follicles once again.
-Possible temporary worsening of alopecia (anecdotal shedding) with some anecdotal reports stating that no regrowth ensued after the shedding period, leaving them worse off than before.
-Side effects: While this study (PMID: 2826267) was performed in vitro and therefore we cannot draw definitive conclusions based on it until an in vivo study is performed, it mentions how minoxidil can inhibit collagen synthesis via lysyl hydroxylase inhibition and anecdotal reports have mentioned side effects of minoxidil that include increased wrinkles, dark circles under eyes and general acceleration of facial aging, while further trials need to take place to assume correlation, the evidence we have now is enough to provide me with yet another reason not to use minoxidil since I value my youthful facial appearance and skin quality greatly.
-As if the aforementioned reasons weren’t enough, lack of pharmacological ability to treat the underlying cause of androgenic alopecia, follicular miniaturisation via susceptibility to DHT is probably the biggest caveat of minoxidil therapy.
In short, minoxidil is far from a stellar product and in my opinion not absolutely necessary unless you are at the point where you absolutely need any benefit you can reap for your hair loss (e.g. grade III+ on the Hamilton-Norwood scale.))
This bit of advice is for the lurkers and the unaware. While it seems many sufferers of androgenic alopecia choose to use azelaic acid as a potential treatment, I caution them due to it’s lack of proven effectiveness for androgenic alopecia. While azelaic acid may hold promise for alopecia areata, the only studies relating azelaic acid to androgenic alopecia was one study that concluded that azelaic acid acts as a 5α-reductase inhibitor in vitro while cautioning the readers with a final statement of ‘if this inhibition is confirmed in vivo, zinc sulphate combined with azelaic acid could be an effective agent in the treatment of androgen related pathology of human skin’ and somehow many patients with androgenic alopecia seem to forgo this warning and assumed azelaic acid was “clinically proven” to work for androgenic alopecia. (PMID: 3207614)
My ultimate goal is to regrow my 17 year old hairline (which looks more or less the same as my 19 year old hairline in the November 2014 photo) but I understand that this is unrealistic statistically speaking. Even if I can only achieve maintenance with this regimen I will still be pleased. I'll post an update 6 months from now unless of course I see noticeable results earlier.
Also please let me know what Norwood you think I am, I'm not good at reading that scale at all.
I am a 20-year-old male, 186 cm, 73 kg, Mediterranean descent, moderate drinker (7-21 units of ethanol per week), occasional non-habitual smoker (1-5 packs per year spread out throughout the year) and board certified pharmacy technician.
Supplements:
Daily: Centrum Men’s Multivitamin, Nature’s Own Triple Concentrated Fish Oil, Vitamin D3 1000 IU as cholecalciferol 25 mcg, Biotin 300-5000 mcg
3-5x per week: AllMax Nutrition Quickmass (contains 3.86 g creatine per serving)
PRN: choline bitartrate 100mg, Coenzyme Q10 100mg, No-Doz Plus, Vivarin, ephedrine, 2mg Nicorette gum, melatonin 1-10mg
5-6 months per year @ 3x per week: BSN N.O. Xplode pre-workout supplement (contains 2.5 g creatine per serving), Acetyl-L-Carnitine or L-Carnitine 500mg
Hair products:
-Silicone-free shampoo and conditioner (when not using Nizoral)
-Various styling products (mostly wax, paste or mousse)
There are known incidences of androgenic alopecia on my paternal side of the family, with my father having a Norwood grade I hairline at 62 years of age and my father’s brother being Norwood grade VII at age 55 with progression unknown. Only one incidence of advanced androgenic alopecia on my maternal side of the family, my maternal grandfather was at Norwood grade III until his early 40s and then progressed fully to Norwood grade VII shortly afterwards, my maternal grandfather did have type II diabetes but was otherwise in good health. My mother’s brothers progressed to Norwood grade II to III late in life, around age 40-50.
Treatment timeline:
(Studies can be found on Google by copying and pasting the study IDs I've mentioned)
I’ve been experiencing mild hair loss, first noticed at 19 years of age around April 2014, seeing slightly more hair on my hands in the shower after applying shampoo and conditioner (thankfully not in clumps but rather single strands).
Hair loss slowly worsened over the course of the year, especially so after my 20th birthday (September of 2014). I initially presented to my dermatologist with seborrhoeic dermatitis in early November 2014 (which is also when I began lurking on this forum) and was prescribed ciclopirox olamine 1.5% w/w shampoo in the form of Stieprox, after several months no regrowth was noticed, only worsening of hair loss.
I experienced a relapse of seborrhoeic dermatitis in mid-March 2015 and was treated with ketoconazole 2% w/w shampoo in the form of Nizoral with good success and there has been no further relapse of seborrhoeic dermatitis due to once a week prophylactic antifungal therapy with either Nizoral or Stieprox, with Stieprox being used more often due to its refreshing scent. Hair loss continued to worsen, albeit slowly, noticing hairs on my pillow at this point, similar to the hair I found on my hands in the shower, the hairs present on my pillow were also strands and not clumps.
To rule out any other possible causes of hair loss I requested that my GP perform several blood tests as follows:
Comprehensive metabolic panel with lipid profile, complete blood cell count, thyroid function test panel, iron studies, serum zinc, serum magnesium and comprehensive male hormone panel (I'm at uni now and will update the exact values for this panel when I get home as I left the envelope with the test results back home). All came back within their normal reference ranges save for the serum zinc test which actually came back slightly higher than normal, but not high enough to interfere with copper levels (which would’ve showed up as an abnormality in the iron studies since copper is essential for iron metabolism)
I visited my dermatologist once again during mid July 2015 to assess the degree of hair loss, dermatologist’s opinion as follows: androgenic alopecia unlikely but is unable to make a definitive diagnosis at this point due to the patient’s young age. After performing a pull test, examining the scalp and taking photos and measurements of the hairline the dermatologist concluded that my hair loss is not advanced enough to be graded on the Hamilton-Norwood scale, with the dermatologist specifically stating that my hairline hasn’t receded enough to look like Norwood grade I. (I understand there is no such thing as NW0 but I’m just going by what the dermatologist said verbatim)
I then asked ophthalmologist about the removal of one of my topical ophthalmic medications that I take daily (I have ocular hypertension), timolol maleate 0.5% to which he approves, since beta-blockers are sometimes an etiology of alopecia, after one month of cessation I noticed no improvement and continual worsening of hair loss. Interestingly enough, I also take latanoprost ophthalmic, which belongs to a class of medications called prostaglandin analogues, currently being studied as a future treatment for androgenic alopecia, with another drug in a similar class (prostamides), bimatoprost (Lumigan), being marketed as a treatment that lengthens eyelashes under the brand name Latisse. It may be of note that while timolol wasn’t causing my alopecia, at least not to the same degree as in this case report (http://www.reviewofophthalmology.com/content/d/features/i/1317/c/25352/ as you can see, even when this patient discontinued timolol and recovered, he still remained NW2-3, meaning that the cause of timolol related hair loss is androgen independent and henceforth male pattern alopecia alone is not grounds for ceasing timolol treatment) it definitely could’ve triggered the onset of androgenic alopecia, which is mentioned on the American Hair Loss Association’s website as a mechanism of drug induced hair loss: (http://www.americanhairloss.org/drug_induced_hair_loss/).
Around early August 2015, I notice my hair loss worsening especially around the temples. It is likely that I am now at the point where my hair loss can be assessed on the Hamilton-Norwood scale, since the hair loss is not marked and is in the early stages I’m likely classed as Norwood grade I. (I’m going by what the scale’s pictures look like, I may very well be NW2 but to be honest the scale isn’t exactly easy to interpret, do tell me what you guys think based on the attached photos, with an extra one of my crown that I took today after I got my haircut for clarification as I'm unsure if I'm actually thinning back there or not. I've also attached a photo of my hairline the way it was back in mid November 2014 before any major loss occured) Having ruled out all other possible causes of alopecia (medication induced, malnutrition, thyroid pathologies) I decide to undertake treatment for androgenic alopecia after a diagnosis of exclusion and noticing the characteristic ‘male pattern’ presentation of my hair loss. Treatment regimen with my reasoning for use as follows:
Ketoconazole:
Ketoconazole 2% shampoo treatment in the form of Nizoral 2% began on 16 August 2015 with twice weekly 5 minute applications while showering indefinitely to inhibit dihydrotestosterone (DHT) activity in the scalp via dual pharmacological mechanisms, acting as an antagonist at the androgen receptor so as to not allow DHT to bind to the receptor and hence cause damage to hair follicles and inhibition of the 17α-hydroxylase/CYP17A1 enzyme which prevents the synthesis of DHT. As well as antiandrogen activity, ketoconazole 2% shampoo has also proven to be more effective than minoxidil 2% in stimulating hair growth, providing an 18% increase in hair density versus minoxidil 2%’s 11%. (PMID: 9669136)
Many people have marked concern about ketoconazole 2% shampoo’s ability to be systemically absorbed, this is unfounded due to the fact that the package insert for Nizoral brand ketoconazole 2% shampoo clearly states that plasma concentrations of ketoconazole were not detectable after topical administration on the scalp while plasma levels were detected after topical administration on the entire body. Therefore systemic side effects should be non-existent if one is using ketoconazole 2% shampoo as intended.
Another concern regarding ketoconazole 2% shampoo is its frequency of use. Countless forum users have said ‘why do we only need to use it twice a week when other hair loss treatments we use every day”. The answer is simple; ketoconazole persists at therapeutic concentrations in the epidermal layers anywhere from 4-10 days, forgoing the need for daily use. (Kucers' The Use of Antibiotics Sixth Edition) This is due to its lipophilic nature and strong affinity for protein binding (read: keratin in the hair and scalp)
"Following a single application of ketoconazole shampoo, ketoconazole persists at therapeutic concentrations for 7 days in the epidermal layers. In addition, substantial pityrosporal inhibitory doses of ketoconazole were detected on the hair for several days after use of the shampoo, the mean level at 72 h was 11.6 µ mg."
(Pierard GE, Arrese JE, Pierard-Franchimont C, et al: Prolonged effects of antidandruff shampoos-time to recurrence of Malassezia ovalis colonization of skin. International Journal of Cosmetic Science. 1997;19:111-117.)
Again, if there’s any doubt in the treatment’s efficacy, look to the studies, where in one of them patients were only using the shampoo 2-4 times a week to achieve better results than daily 2% minoxidil use.
Lastly people seem to wonder if ketoconazole shampoo is ‘worth the hassle’. To be honest, I don’t see the inconvenience, we have to use shampoo in the shower anyway, and it only serves to conserve our normal shampoo if we use Nizoral twice a week. As well as controlling hair loss, I’ve personally had seborrhoeic dermatitis in the past and hence need to use an antifungal shampoo once a week indefinitely for prophylaxis to prevent a relapse of the condition, so for me using Nizoral is something I have to do regardless, so I figure it’s even easier to simply increase my usage to twice a week.
Spironolactone:
Spironolactone 5% topical cream treatment began on 30 August 2015 with twice daily applications indefinitely to inhibit DHT activity in the scalp via the same two mechanisms as ketoconazole albeit with much greater potency: androgen receptor antagonism and inhibition of the CYP17A1 enzyme as well as having three additional pharmacological mechanisms: progesterone receptor agonism which results in antigonadotropin effects, indirect estrogenic effects which increase the level of sex hormone binding globulin (SHBG binds to testosterone and hence lowers free T levels, therefore lowering the amount of free T converted to DHT) and the amount of testosterone converted to estradiol (meaning less T converted to DHT) and weak 5α-reductase inhibition (these last two lesser known mechanisms of spironolactone are supported via these studies: PMID: 7829618, PMID: 4033118, PMCID: PMC2923944)
I understand spironolactone can cause feminising effects when taken orally by men and hence most spironolactone studies are done only on women but while uncommon, the topical formulation has been proven in an older study on men and in a recent study on women to be effective for androgenic alopecia (alfatradiol is another antiandrogen that is effective for both men and women suffering from androgenic alopecia and it is clear that spironolactone is no different). It has also been proven that topical spironolactone is not absorbed systemically and hence has no endocrine systemic side effects. One of the studies showed even after applying 5% spironolactone cream to 55% of the patient’s body area, plasma canrenone levels (canrenone is the major metabolite of spironolactone) were undetectable during the 72 hours of treatment. Plasma levels of various hormones were measured both before and after application and also proved to be unaffected. (PMID: 3411088)
The specific topical spironolactone brand that I will be using is S5 Day Cream and will implement S5 Bedtime Cream after 2 months of use of the Day Cream. The reason being is to allow sufficient time to perform an allergy test and assess whether I tolerate the medication well (i.e. don't get a rash).
While some people are skeptical about the legitimacy of S5 cream and some even questioning its spironolactone content (a few people wondering if it even contains any spironolactone at all) all I have to say to that is that a decent trick to tell if spironolactone is present is its notorious odour. Being a drug that’s molecular structure contains a sulphur atom; it has a mercaptan-like odour, often described by many as a ‘rotten egg’ smell. I personally can confirm that S5 cream has this specific odour, although you can tell it’s been masked with limonene, resulting in a bit of a combination smell.
The vehicle used in S5 cream also comes under fire in various internet forums with many exclaiming ‘how do we know spironolactone is even absorbed at all’, this is also unfounded because the vehicle used for S5 (alcohol and triethanolamine) is the same as the vehicle used by compounding pharmacies who also make topical spironolactone formulations.
(Reference from this compounding pharmacy’s specific spironolactone formulation ID: US Pharm. 2012;37(12):43-44)
S5 Day Cream contains 1% caffeine in addition to 5% spironolactone; the addition of caffeine is thought to provide additional benefits for hair loss although further in vivo studies are needed to prove said benefits. (Evidence from in vitro studies showing stimulation of hair growth, suppression of androgen activity and 5α-reductase inhibition: PMID: 23075568, PMID: 24836650, PMID: 17214716)
S5 Bedtime cream contains no caffeine but instead includes 1% adenosine in addition to 5% spironolactone; the addition of adenosine is proven to provide benefits for hair loss with good evidence from studies done in humans, with results including thickening of hair density and one study even showing that topical adenosine in a 0.75% formulation was only slightly less effective than 5% minoxidil, with patients being more satisfied with the results from adenosine. (PMID: 24183218, PMID: 25925959)
It should be worth mentioning that while DHT is the pinnacle cause of androgenic alopecia, it is currently unknown whether other androgens have a pathological role. What we do know as of now is even those who are taking finasteride or even the potent dutasteride, some still inexplicably continue to lose hair and when a male with androgenic alopecia is castrated, said hair loss ceases to continue, this serves to suggest that other harmful androgens possibly have a lesser pathological role. With this in mind, androgen receptor antagonists such as ketoconazole and spironolactone offer peace of mind due to the fact that in addition to preventing DHT from binding to the androgen receptor, they also will prevent any other potentially harmful androgens from doing so as well.
Should hair loss not be controlled via the current treatment regimen, I will reassess after one year has elapsed and decide whether to add a topical 5α-reductase inhibitor such as alfatradiol. (References for effectiveness of topical alfatradiol: PMID: 7398983, PMID: 17451383, PMCID: PMC3412238)
I will not attempt treatment with minoxidil due to:
-Overall lack of long-term effectiveness as a hair growth stimulant, ending up being slightly better, equal or inferior compared to ketoconazole 2% and adenosine in concentrations of 0.75% and up depending on the concentration of minoxidil used.
-Lack of certain effectiveness since even Regaine/Rogaine’s website states that some minoxidil users only report maintenance or no effect at all (9/10 men kept or regrew hair was the exact statement, meaning it had no effect for 1/10 men and only some of the 9/10 experienced regrowth) and this recent study (PMID: 25112173) showing that the exact percentage of users that experience regrowth is only 40%. In addition, I’ve read Rogaine Foam has shown to provide regrowth in 85% of patients, so it seems results are equivocal.
-Absolute commitment to treatment as discontinuing minoxidil may cause rapid and irreversible loss of any newly grown hair whereas discontinuation of antiandrogens would simply allow DHT to slowly begin miniaturising hair follicles once again.
-Possible temporary worsening of alopecia (anecdotal shedding) with some anecdotal reports stating that no regrowth ensued after the shedding period, leaving them worse off than before.
-Side effects: While this study (PMID: 2826267) was performed in vitro and therefore we cannot draw definitive conclusions based on it until an in vivo study is performed, it mentions how minoxidil can inhibit collagen synthesis via lysyl hydroxylase inhibition and anecdotal reports have mentioned side effects of minoxidil that include increased wrinkles, dark circles under eyes and general acceleration of facial aging, while further trials need to take place to assume correlation, the evidence we have now is enough to provide me with yet another reason not to use minoxidil since I value my youthful facial appearance and skin quality greatly.
-As if the aforementioned reasons weren’t enough, lack of pharmacological ability to treat the underlying cause of androgenic alopecia, follicular miniaturisation via susceptibility to DHT is probably the biggest caveat of minoxidil therapy.
In short, minoxidil is far from a stellar product and in my opinion not absolutely necessary unless you are at the point where you absolutely need any benefit you can reap for your hair loss (e.g. grade III+ on the Hamilton-Norwood scale.))
This bit of advice is for the lurkers and the unaware. While it seems many sufferers of androgenic alopecia choose to use azelaic acid as a potential treatment, I caution them due to it’s lack of proven effectiveness for androgenic alopecia. While azelaic acid may hold promise for alopecia areata, the only studies relating azelaic acid to androgenic alopecia was one study that concluded that azelaic acid acts as a 5α-reductase inhibitor in vitro while cautioning the readers with a final statement of ‘if this inhibition is confirmed in vivo, zinc sulphate combined with azelaic acid could be an effective agent in the treatment of androgen related pathology of human skin’ and somehow many patients with androgenic alopecia seem to forgo this warning and assumed azelaic acid was “clinically proven” to work for androgenic alopecia. (PMID: 3207614)
My ultimate goal is to regrow my 17 year old hairline (which looks more or less the same as my 19 year old hairline in the November 2014 photo) but I understand that this is unrealistic statistically speaking. Even if I can only achieve maintenance with this regimen I will still be pleased. I'll post an update 6 months from now unless of course I see noticeable results earlier.
Also please let me know what Norwood you think I am, I'm not good at reading that scale at all.
