Higher Minoxidil Concentrations: Is More Always Better?

10 % Topical Minoxidil vs 5 % Topical Minoxidil: Which is better?

Minoxidil is FDA approved for treating androgenetic alopecia (male pattern balding and female pattern hair loss). It would seem logical to propose that if the drug minoxidil helps in the treatment of males and females with androgenetic alopecia that more minoxidil should help even more.

Researchers from Egypt set out to compare the efficacy and safety of 5% topical minoxidil with 10% topical minoxidil and placebo in 90 males with balding.  The study was a double-blind placebo controlled randomized trial over 36 weeks. The study comprised three treatment groups: 1) study participants receiving 5 % minoxidil 2) study participants receiving 10 % minoxidil and 3) study participants receiving placebo.

Surprisingly, after the 9 months, partipcants in the 5 % minoxidil group had higher vertex and frontal hair counts compared to study participants in the 10 % minoxidil group and the placebo group.

Conclusion

This was a nice study showing us that even after 40 years of studying minoxidil, we still have a lot to learn and a long way to go. Higher concentrations of minoxidil are not necessarily better - although more studies are clearly needed.

Reference

Ghonemy S et al. Efficacy and safety of a new 10% topical minoxidil versus 5% topicalminoxidil and placebo in the treatment of male androgenetic alopecia: a trichoscopic evaluation. J Dermatolog Treat. 2019 Oct 21:1-6. doi: 10.1080/09546634.2019.1654070. [Epub ahead of print]

Is Androgenetic Alopecia (AGA) Caused Only by the Effects of DHT ?

Despite the Myth, Androgenetic Alopecia is Not Simply a Story of DHT

Androgenetic alopecia is a type of hair loss that affects men and women. In males, this condition is also referred to as male balding or male pattern hair loss and eventually affects some 80 to 90 % of males. In females, the condition is referred to as female pattern hair loss or simply hair thinning and affects 40% of women by age 50. The purpose of this article is to deal with some misconceptions, wrong information, errors and myths that many people have about the role of DHT in the balding process. DHT is certainly important - but other factors must be considered too.

The Evolution of the DHT Theory of Male Balding

Some of the earliest observations about the role of hormones in male balding happened in the time of Aristotle back in 300 BC. Aristotle showed that castrated males (eunuchs) did not develop balding. JB Hamilton in 1942 did additional pioneering work to understand male balding. He showed that male hormones are relevant to the balding process. Specifically, he confirmed observations by Aristotle and others that males that were castrated before puberty did not go on to develop balding. Hamilton took this further and showed that if testosterone was given back to castrated males, the males proceeded to develop male balding. This showed that male balding was an “androgen-dependent” process.

Further key work in understanding male balding was done in the 1970s and ultimately published in the New England Journal of Medicine. These were studies that showed that male pseudohermaphrodite living in the Dominican Republic with a genetic deficiency known as 5 alpha reductase deficiency did not produce dihydrotestosterone (DHT) and did not develop male balding. These findings lead ultimately to the rational development of drugs such as finasteride and dutasteride which block 5 alpha reductase and lower DHT levels.

The Story of Male Pattern Balding has a DHT Chapter but Don't Forget to Read the Others

From 300 BC to the 1990’s, the story of male balding seemed pretty clear. Male hormones, particularly the infamous DHT, seemed to be what male balding was all about. Blocking DHT was what treatments were all about.

Many people incorrectly assume that male balding is just a DHT story. Many people incorrectly assume that this DHT chapter is the only chapter they need to read when trying to understand male balding. While it’s true that DHT has a whole lot to do with male balding - the correct way to state it is “male balding is due in part to the effects DHT on hair follicles that are genetically sensitive to this hormone.”

DHT not the only chapter in the balding story

DHT not the only chapter in the balding story. One only need to consider a few other treatments that are used for balding to very quickly realize that male balding must be much more complex than just a DHT story. Minoxidil (Rogaine), for example, has nothing to do with DHT - and yet it helps some people with male balding. Granted I agree that finasteride and dutasteride are much much better treatments than minoxidil - but if DHT was the only thing we need to think about when it comes to treating male balding then minoxidil would not be expected to have any sort of benefit. Well, it does. Low level laser therapy also has nothing to do with DHT hormone levels - and yet it helps some males with their male balding. Platelet rich plasma (PRP) also has very little to do with DHT- and yet it helps some males with their male balding.

Drug Companies are Investing Large Sums with the Knowledge that Male Balding is Far Far More than A Simply DHT Story.

At least 12 pharmaceutical companies are investing millions upon millions of dollars with the clear understanding that DHT is not the only chapter in the balding storybook. These companies are hoping to the first to market with brand new types of drugs - again drugs that have nothing really to do with DHT. A brief summary of the drugs is below.

If Male AGA is Far More than A Simply DHT Story, Female AGA is Far Far Far More than A DHT Story

If you have now come to realize that male balding is a bit more complex than simply a story about DHT, I’d like to point out that female androgenetic alopecia (i.e. female pattern hair loss) is even more complex. If you think for even a moment that you’re going to apply the same DHT story that you used in males to explain balding to the mechanisms operating in females with androgenetic alopecia, you’re going to come up short in terms of your ability to explain hair thinning in women.

Androgenetic alopecia in females is a far more complex story - and we still don’t know all of the mechanisms that govern how hairs thin in women. Of course, there is some aspects of the DHT story that relevant to female thinning. But finasteride and spironolactone and anti-androgens are far less consistently helpful in females than in males. Other treatments such as minoxidil and laser may be far more helpful in some women than in males. In other words, there are likely several different mechanisms that are contributory to androgenetic alopecia in females besides simply a DHT story. As further information for reflection to readers who still doubt this information, one must consider that some women with a genetic condition that completely makes them insensitive to the effects of androgens (called androgen insensitivity syndrome) can still develop androgenetic alopecia. Even women with low testosterone and low DHT levels can develop androgenetic alopecia. There are even some androgen deficient women who do not develop any balding whatsoever when you give them back supplemental androgens through various means of testosterone replacement therapy.

Conclusion

Is androgenetic alopecia simply due to the sensitivity of hair follicles to DHT? Well, it’s a good story, but it’s only part of the story. The DHT chapter is an important chapter to read in the story of male balding and female thinning, but be sure to read the remaining chapters of the story book. The DHT story is not the only story - and many pharmaceutical companies are banking on this concept.

Is Immunotherapy (DPCP, SADBE) Effective for Lichen Planopilaris or Frontal Fibrosing Alopecia ?

Immunotherapy (DPCP, SADBE) Does NOT Help Scarring Alopecia

Diphencyprone (DPCP) and Squaric Acid Dibutyl Ester (SADBE) are long standing treatments for the autoimmune hair loss condition alopecia areata. The cause itching and burning in the scalp and essentially trigger an allergic contact dermatitis. The inflammation that these chemicals create can trigger hair growth in some patients with alopecia areata. It’s quite remarkable.

FIGURE 1. Diphenycyprone (DPCP) is a liquid that is applied to the scalp to treat alopecia areata. It causes an allergic reaction but can stimulate hair growth in some users.

FIGURE 2: Hair Regrowth in a patient with ‘ophiasis” type of alopecia areata who was treated with diphenyprone.

Does DPCP and Squaric Acid Help Lichen Planopilaris or Frontal Fibrosing Alopecia (FFA)?

DPCP and Squaric acid are not effective in these scarring alopecias. It’s not that large studies have been done - it’s just that I’ve seen patients many patients over the years with scarring alopecias who have come to see my after having DPCP. These patients were all mistakenly diagnosed as having alopecia areata when really they had frontal fibrosing alopecia or lichen planopilaris. Hair regrowth did not occur and many experiencing a significant worsening.

FIGURE 3: Patient with frontal fibrosing alopecia who was first thought to have the ophiasis form of alopecia areata and was treated with DCPC for many months. The patient did not experience regrowth.

There is absolutely no reason to believe that DPCP or squaric acid are effective in LPP or FFA. The pathogenesis of these two conditions is very different than alopecia areata. While it’s true that some treatments overlap - many do not. The following table summarizes some of these important differences. DPCP is effective for some patients with alopecia areata but is not effective in LPP. Doxycycline is effective for some patients withLPP but not helpful in treating alopecia areata.

Table 1: Treatments in Alopecia Areata vs Lichen Planopilaris

Reference

[1] DPCP for Hair Loss: Can I Apply it at Home?

Prescribing Dutasteride in Males with Balding: Are there any criteria ? Should there be any criteria?

Prescribing Dutasteride in Males

The most effective medical treatments for male balding (at the time of this article being written) are oral finasteride and oral dutasteride. There is no debate about this particular comment. In the present day, as the world grapples with the meaning of “post finasteride syndrome”, dutasteride is increasingly a choice for many physicians where it never might have been a choice before. I see it - and I see more now than I did 2 years ago. I see dutasteride being used and 0.5 mg three times weekly. I see dutasteride used at 2.5 mg once weekly or twice weekly. I see dutasteride being used at 0.5 mg daily. I see dutasteride being used more often - and I too prescribe it more now than I did 10 years ago.

Dutasteride is not formally FDA approved for treating male balding but is still widely used. It’s used “off label” though and certainly has a large number of studies to back up its effectiveness. In some countries, dutasteride does have formal approval.

The public is also increasing asking about dutasteride - and increasingly requesting it. After all, we don’t have a great deal of data implicating dutasteride in the same set of issues that finasteride has. Furthermore, it’s more effective than finasteride. These two points lead many to turn to the drug. Some data suggests side effects like sexual dysfunction are greater with dutasteride than finasteride but certainly not all studies show this. Some in fact, show that side effects of dutasteride are similar to placebo.

We don’t yet fully understand everything behind post finasteride syndrome to even begin to dig into what might be called a post dutasteride syndrome or a general 5 alpha reductase syndrome. More studies are needed.

So, will you prescribe me dutasteride or not?

Many patients come in the clinic wanting to know if I’ll prescribe them dutasteride. Some have been on finasteride and haven’t found that it works - and they want dutasteride. Some don’t want to try finasteride at all - they want dutasteride. Some want both. Some know the dose they want.

it all comes down to understanding the medical evidence and the 20 years of science that comes before. There is not a “yes” or “no” answer to whether I will prescribe dutasteride. I don’t know when a patient walks in the door if these medications are right for them - but I do know before the patient walks out the door if these medications are right for them.

The following are the criteria I use in the clinic for determine if the patient is a candidate for dutasteride. These are my criteria and may not necessary be the guideline principles for everyone.

Top 10 Criteria for Prescribing Dutasteride (Donovan)

1. The patient understands the treatment is life-long if he wishes to maintain active medical treatment of his androgenetic alopecia.

2. The patient is aware of the array of possible side effects that have been reported with use of 5 alpha reductase inhibitors including mood changes, depression, anxiety, sexual dysfunction, enlargement of breast tissue (gynecomastia), penile shrinkage, loss of penile sensation, weight gain, muscle weakness and others. The potential effects of dutasteride on males wishing to father are not completely understood. The patient accepts the risk of these side effects if he chooses to use dutasteride.

3. The patient does not currently have severe depression or currently have severe anxiety that might otherwise present a contraindication to using dutasteride. The patient has not been suicidal in the past or been hospitalized for depression and mental illness within the past 5 years.

4. The patient is aware of reports that some patients have experienced persistent (long lasting) problems even when the drug has been stopped. These are mainly studied in the context of finasteride but should be assumed for now to be relevant to the use of dutasteride. The patient accepts the risk of these side effects if he chooses to use dutasteride.

5. The patient is aware that class action lawsuits have been launched regarding the persistent side effects related to finasteride use.

6. The patient is aware of alternatives for treatment including topical minoxidil, oral minoxidil, topical anti androgens (topical finasteride), low level laser, platelet rich plasma and hair transplantation.

7. The patient has no known issues currently related to male inferility or infertility in a female partner.

8. The patient understands the possibility of dutasteride causing a reduction in sperm count and the rare possibility that these reductions may be permanent or long lasting (even when the drug is stopped). The original dutasteride studies showed that after 6 months of stopping the drug, sperm counts had not returned to normal in all study participants and that the total sperm count in the dutasteride group remained 23% lower than baseline.

   Males who are concerned about the possibility of lower sperm count or fertility issues may consider having baseline semen analysis or baseline FSH, LH, Free T4 and testosterone measurements before starting. These lab tests may provide some guidance about baseline fertility. These issues in point 5 are relevant to males who may wish to father children in the future.

9. The patient does not wish to donate blood and understands that blood donation is not possible for at least 6 months after stopping the drug.

10. The patient understands that dutasteride may affect future prostate cancer screening by affecting the PSA value. These issues need to be discussed at the time of such screen and consideration might be given to baseline screening depending on the age of the patient when starting dutasteride.

Conclusion

I can’t say if a patient is a candidate for starting dutasteride when they walk in the office but after 20-30 minutes I can determine if they are likely to be a good candidate for the drug or not. The answers to the questions and issues above help guide the decision making that goes into figuring out if a patient is a candidate for dutasteride or not. It’s not something that can be ascertained in a matter of a few minutes.

References

Meeker JD, Godfrey-Bailey L, Hauser R. Relationships between serum hormone levels and semen quality among men from an infertility clinic. J Androl 2007;28:397–406.

Topical Tofacitinib for Alopecia Areata: How much does it really help?

2% Ointment Helped 1 of 10 Patients 

Oral tofacifitinb belongs to a group of medications known as JAK inhibitors and represents an off-label treatment for alopecia areata.  Its use is limited by cost but also by potential side effects associated with its immunosuppressive effects. An increasing interest is mounting regarding the potential use of topical JAK inhibitors in treating alopecia areata.

The optimal formulation (liposomal vs ointment) has yet to be definitively proven. Previous studies have suggested a benefit of both topical ruxolitinib and topical tofacitinib in at least some patients with alopecia areata. 

New Study Examines Topical Tofacitinib

Researchers from Yale set out to examine the benefit of tofacitinib ointment in adults with alopecia areata. In their report, the authors described the results of a 24-week, open-label, single-center pilot study of 10 patients with AA treated with tofacitinib 2% ointment applied twice daily.  Patents were eligible for the study if they were 18-years-old or older, had at least 2 patches of alopecia areata, had  stable or worsening disease for 6 months, and have received no treatment for AA for at least 1 month prior enrolment. Tofacitinib was applied to half of the involved scalp and, if and when evidence of hair regrowth was observed, tofacitinib was subsequently applied to the entire involved scalp. 

 

What were the results?

The authors showed that 3 of 10 subjects experienced hair regrowth with topical tofacitinib with a mean decrease of 34.6% in SALT score (standard deviation 23.2%).  Of these three patients, only one had excellent regrowth. 2 others had partial growth. Skin irritation was reported by 40 % of patient and folliculitis in 10 %. Both of theses side effects resolved even without treatment. 40 % of patients had a minor increase in cholesterol levels. Despite these minor side effects there were no serious side effects. 

Conclusion and Summary

This is an interesting study by these Yale researchers who are leaders in this area of JAK inhibitors. It was disappointing that only 1 of 10 patients had significant improvement.  Whether a differential topical vehicle (such as a liposomal vehicle) could have different results awaits further study.  The main message of all of the topical JAK inhibitors studies to date is that they could help some patients with alopecia areata, but for many they do not. 

REFERENCE

1. Liu L et al. Tofacitinib 2% ointment, a topical janus kinase inhibitor, for the treatment of alopecia areata: a pilot study of 10 patients. Journal of the American Academy of Dermatology.

DOI: http://dx.doi.org/10.1016/j.jaad.2017.10.043

2. Topical Ruxolitinib Promotes Eyebrow Regrowth in Alopecia Universalis  

3. Topical JAK inhibitors for Children and Adolescents with AA  

Topical Finasteride: Are side effects possible?

Topical Finasteride: Don't forget the placebo studies!

If one is going to use topical finasteride,  they must be 'prepared' for the possibility of side effects. For patients to use topical finastseride (or physicians to prescribe topical finasteride) with the complete expectation that it comes with zero chance of side effects is simply incorrect. The "chances" of side effects in my experience are certainly very, very, very low (probably well under 1 in 1000) and much, much lower than oral finasteride. But they are likely not zero especially if one considers that even placebo pills have side effects! Side effects with topical finasteride have not been reported to date.

 

Topical finasteride: What is the risk of side effects?

Common sense dictates that someone will have a side effect to topical finasteride. Whether it's 1: 1000 men or 1 in 10,000 or 1: 1,000,000 is unknown but there is little doubt in my mind that side effects are possible. We know that DHT is still inhibited in the blood by up to 25 % with some topical finasteride formulations and about one tenth of the amount of finasteride is still absorbed. In other words, a lot less gets into the blood, but it's far from zero. 

 

Analogies I use in my clinic

I completely understand that many physicians and many patients assume that topical finasteride is 100 % free of side effects (or at least close to it). But let's use a few analogies which help us all understand that a 25 % reduction in DHT is going to be a bit much for a small proportion of men.

Humans have a delicate physiology. There are some individuals that are sensitive to small changes in blood levels of anything. There are some individuals that are sensitive to small amounts of alcohol in the blood. Some individuals are sensitive to small amounts of caffeine.

Sexual physiology is likely even more complex. There is no doubt that some will be sensitive to small reductions in DHT. We see similar "DHT" related side effects even with saw palmetto - which is not supposed to even effects DHT at all! We even see DHT related side effects (erectile dysfunction, decreased libido) in 0.7 % of men using "placebo pills" in clinical studies - which inhibit DHT 0 %!! By age 30, about 30 % of men have some degree of sexual dysfunction. By age 50, it's 50 % , and by age 80, it's well over 80 % of men.  Factor this into the 0.7 % chance of sexual-related side effects with placebo pills and it's easy to understand that at least someone is going to present with concerns about side effects from topical finasteride. 

Consider now the following table. We know that oral finasteride inhibits DHT by 70 % based one studied done in the 1990s. The chances of side effects with oral finasteride are around 2 %. This includes sexual dysfunction and mood changes. A drug that inhibits DHT to no degree at all (i.e. 0%) would likely have lower chances of "DHT-related" side effects. But clinical studies using placebo pills in clinical trials of finasteride have suggested this could be as high as 0.7 %. Of course, other side effects could be possible.  We are then left with considering the chances of side effects in a drug that inhibitors DHT levels in the blood by 25 %. Are the chances of side effects zero? Probably not given that not even the placebo has a 0 % chance of side effects.. But fortunately, they are likely very low. We don't yet know that number. In my experience using topical finasteride, I have formed the opinion that it is likely very low and probably well under 1:000. But what is the real number? Is is 1:1000 men?  1:10,000 men?

 

.Many different Topical Finasteride Formulations

If a male is very sensitive to a reduction in DHT then side effects may occur. If a formulation can be created with zero penetration into the blood then systemic DHT will not be affected. That does not exist yet. One must keep in mind that there is no "one" topical finasteride formula - there are dozens of different formulations. Some pharmacies just make it up however, they like. Polychem is studying a specific formulation. MorrF is available in India already through Intas Pharmaceuticals and consists of topical minoxidil and topical finasteride together. .

Topical finasteride is clearly safer than oral finasteride and we have used for several years in our clinic. To say it has zero possible side effects would be incorrect. In my opinion, it is just a matter of time before we hear of possible side effects.  There are side effects even with placebo (and it's as high as 0.7 %!).But overall, topical finasteride is much much safer than oral finasteride. But anyone who uses it must be aware that it is off label and long term effects are not known. There have been millions of prescriptions for oral finasteride to date and well over 1 million men use it every year for treating hair loss. This does not include finasteride use in prostate issues. Compare this to the fact that there are probably under 200,000 men worldwide (maybe quite a bit less) that have used topical finasteride. 

Physicians and patients need to be aware of the 'unknowns' of topical finasteride use and  counsel patients on the reduced chances of side effects but the possibility that a very small proportion of men will report side effects. Overall, the drug appears to have a very good safety profile in the topical formulation.

REFERENCES

M Caserini, et. al.  A novel finasteride 0.25% topical solution for androgenetic alopecia: pharmacokinetics and effects on plasma androgen levels. Int J Clin Pharm Th July 30, 2014 (1-8).

BS Chandrashekar, et. al. Topical minoxidil fortified with finasteride: An account of maintenance of hair density after replacing oral finasteride. Indian Dermatol Online J 2015 Jan-Feb; 6(1): 17-20.

S Sheikh, et. al.  A new topical formulation of minoxidil and finasteride improves hair growth in men with androgenetic alopecia. J Clin Exp Dermatol Res 2015, 6:1.

Saw Palmetto: What are the side effects?

Saw Palmetto Side Effects

Saw palmetto (serenoa repens) is a natural herbal-based product commonly used for prostate problems in men and hair loss in men and women. 

A number of studies have suggested that saw palmetto can help hair loss. These studies are small and few in number. Nevertheless, countless numbers of patients turn to these natural products. Furthermore, because they are natural, most assume they are without side effects. The side effect profile of saw palmetto is not entirely clear. It is however known that saw palmetto affects hormones in the body, and risks of mood changes like depression and sexual dysfunction may be real (albeit low) risk.

A recent report provided additional evidence that this natural product might best be classified among chemicals and molecules that affect the hormone and endocrine system of the body (so called "endocrine disruptors"). A 2015 paper from Italy reported development of hot flashes in a 10-year-old girl using saw palmetto. When she stopped treatment, the hot flashes stopped. When she started back up again ("ie a rechallenge'), the hot flashes returned. However, 4 months after starting saw palmetto, the 10 year old got her first menstrual cycle. 

This report reminds us that use of saw palmetto requires counselling of at least the low possibility of side effects. I advise my own patients of the generally well tolerated nature of saw palmetto but remind them of possible risks of mood changes and even the rare possibilities of sexual side effects. More studies are needed to not only document the successes of saw palmetto in medicine but the incidence of side effects.
 

Reference

Morabito et al. Pharmacology 2015.
 

DPCP for alopecia areata: Why do we use acetone to make it up?

Dissolving DPCP in Acetone

Diphencyprone or "DPCP" is a chemical that causes allergic reactions. It is used as an off-label (non FDA approved) treatment for patients with alopecia areata whereby the DPCP is applied directly to the scalp and left on for 24-48 hours. After 48 hours the DPCP is washed off.

DPCP is not soluble in water so it is typically made up in acetone. Acetone is an organic solvent best known as the ingredient in nail polish remover. DPCP may also be soluble in other ingredients such as isopropanol.

What is often forgotten is that DPCP degrades in light and at room temperature. DPCP should be ideally stored at 4 degrees ceclius and protected from light. Usually DPCP is dispensed in brown light proof bottles but I recommend wrapping in aluminum foil to further protect from light.

Am I taking the right amount of hydroxychloroquine (Plaquenil)?

Hydroxychloroquine (Plaquenil): Am I taking too much?

Hydroxychloroquine is an oral medication used in a variety of autoimmune conditions. Side effects have been discussed previously but today we will focus on eye side effects. A number of side effects are possible ranging from vision changes to double vision to asymptomatic changes in various parts of the eye.

The Risk of Retinopathy with Hydroxychloroquine

"Retinopathy" is one of the more worrisome side effects of Hydroxychloroquine. At appropriate doses, studies show that the risk appears to be about 1 % of patients at 5 years of use and 2 % at 10 years. After 20 years, the risk may rise to 20 %. Once the retinal toxicity from hydroxychloroquine occurs, it is believed that the changes in the retina are permanent. Furthermore, the disease can even progress even if hydroxychloroquine is stopped.  

 

Risk Factor for Retinal Toxicity

Retinal damage can occur in anyone. However, the risk may be increased if the following risk factors are present

• Longer Duration of use (cumulative dose)
• Renal or hepatic functional impairment. Compromised kidney and/or liver function can lead to increased accumulation of hydroxychloroquine in the tissues.
• Age over 60 years.
• Preexisting retinal disease
• Concurrent tamoxifen therapy

What dose should I take?

It's clear that taking the appropriate dose reduces (but does not eliminate) the chance of side effects. The optimal dose is 6.5 mg for every kg of lean body weight (not simply what the patient weighs). "Lean body weight" is essentially the patients expected weight for their height and gender - it does not include the "extra" weight that some might carry. Instead of calculating lean body weight, some clinicians advocate simply using the patient's true body weight and multiplying by 5 (instead of 6.5).  In our clinic we typically dose hydroxychloroquine according to the following grid:

Hydroxychloroquine Dosing

Conclusion

The risk of eye related toxicity is low in the first 5-10 years of hydroxychloroquine use provided the dosing is respected. This study has had great importance as it has further helped to define risk and has encouraged changes in screening guidelines. These guidelines now include an initial examination but dedicated yearly screening to begin only after 5 years in otherwise healthy individuals deemed at low risk for eye problems.

Reference

(1) Melles & Marmor. The Risk of Toxic Retinopathy in Patients on Long-term Hydroxychloroquine Therapy. JAMA Ophthalmolol. 2014;132(12):1453–1460.

Valproate and Hair Loss: Does valproate cause hair loss through an androgen mediated mechanism?

There are many different types of drugs used as mood stabilizers is women with bipolar disorder. Many of these drugs can cause hair loss, albeit with different mechanisms. Common medications used in treating bipolar disorder include lithium, valproate, lamotrigine, topiramate, gabapentin, carbamazepine, oxcarbazepine.

Vaproate and Hyperandrogenism

There is increasing evidence suggests that valproate is associated with isolated features of polycystic ovarian syndrome (PCOS). To study this further, researchers studied three hundred women 18 to 45 years old with bipolar disorder. A comparison was made between the incidence of hyperandrogenism (including hirsutism, acne, male-pattern alopecia, elevated androgens) with oligoamenorrhea that developed while taking valproate versus other types of anticonvulsants drugs (like lamotrigine, topiramate, gabapentin, carbamazepine, oxcarbazepine) and lithium. 

What were the results?

It was interesting that among 230 women who could be evaluated, oligoamenorrhea with hyperandrogenism developed in 9 (10.5%) of 86 women on valproate compared to just 2 (1.4%) of 144 women on nonvalproate anticonvulsants or lithium. This translated into a nearly 8 fold risk of these hyperandrogenism and menstrual cycle changes with valproate. Oligomenorrhea happened within 12 months with valproic acid users.

Conclusion

Once needs to be aware of a possible PCOS like clinical phenomenon and for hair specialists - the development of hyperandrogenism and accelerated AGA in women using valproate for bipolar disorder. More studies are needed to confirm these findings.

Reference

Valproate is associated with new-onset oligoamenorrhea with hyperandrogenism in women with bipolar disorder.

Joffe H, et al. Biol Psychiatry. 2006.

Can drugs accelerate androgenetic alopecia (AGA)?

Medications can potentially accelerate androgenetic alopecia. Common examples are anabolic steroids, the use of testosterone injections and topical androgen gels (commonly used for men with "low testosterone"), androgenic progestins in birth control pills, danazol as well as many other medications.

This individual whose scalp is shown in the picture has been using anabolic steroids for body building and has experienced rapid hair loss mainly due to a conversion of his large terminal hairs (some labelled by green dot) to thinner miniaturized hairs (labelled by yellow dot). Treatment of drug accelerated AGA involves either stopping the androgen or blocking the effects of the androgen on the hair follicle using 5 alpha reductase inhibitors... or both. Less specific treatments like minoxidil may provide some benefit. Many individuals can improve with this plan but full regrowth is unlikely.

Anti-coagulants during hemodialysis: Can they cause hair loss?

Blood Thinners and Hair Loss

Dialysis is a medical procedure used to filter waste from the blood in patients with kidney disease. Close to 500,000 Americans and 25,000 Canadians are receiving dialysis. The most common reasons for dialysis is end stage kidney disease due to diabetes and high blood pressure. 

Hair loss and hair changes occur time to time in patients receiving dialysis. One needs to consider a range of nutritional issues (including protein intake, zinc deficiency, iron deficiency), thyroid abnormalities, as well as hair loss from systemic disease itself (ie. autoimmune disease). The use of medications must be considered. 

Anticoagulants are a group of blood thinning medications used during hemodialysis to prevent blood clotting when blood is filtered through machines. Several different types of anticoalgulants may be used and many can rarely cause hair loss. The mechanism by which they cause hair loss is typically a telogen effluvium although other mechanisms may occur as well. 

Apsner and colleagues, in 2001, reported 5 hemodialysis patients who had hair loss from the low molecular weight heparin blood thinner dalteparin. All patients reported that their hair loss stopped when the dalteparin was stopped and a different method of anticoagulation (regional citrate anticoagulation) was used. 4 of the 5 patients even regained hair. In 2003, Sarris and colleagues reported a hemodialysis patient who had hair loss after switching from one low molecular weight heparin (enoxaparin) to tinzaparin. Hair regrowth resumed after switching back to enoxaparin. 

Conclusion

There are many potential reasons for hair loss in patients receiving hemodialysis. Careful review of all factors is needed. Anticoagulants used during hemodialysis, including the low molecular weight heparins, need to be considered. 

Reference

Sarris E, et al. Am J Kidney Dis. 2003.

Apsner R, et al. Blood. 2001

Nausea with Doxycycline: What strategies can help reduce nausea?

Doxycycline and Nausea

Doxycycline is an antibiotic. It's used of course in treating infections but it is commonly used for a variety of scarring alopecias including lichen planopilaris, frontal fibrosing alopecia, central centrifugal cicatricial alopecia, folliculitis decalvans and sometimes dissecting cellulitis.

The drugs has two important properties: it stops infection and reduces inflammation. For some conditions such as lichen planopilaris, it's the anti-inflammatory properties that are useful. For other conditions such as folliculitis decalvans, it's the anti-bacterial and anti-inflammatory properties that are key. 

The drug has a number of potential side effects even though it is generally well tolerated for most. It can cause nausea, vomitting, sun sensitivity, headaches, increased chance of yeast infections in women, rash. 

Doxycycline and Nausea

Some patients developed considerable nausea with doxycycline. Some will even vomit.  This can be a short term issue for some users which improves over time. For others it is something that continues and may even require the patient to stop the medication.  Anyone with nausea from doxycycline should speak to their prescriber for advice on how to reduce the nausea. 

Tips to reduce nausea

1.  Take doxycycline with food. Unlike tetracycline, doxycycline still gets absorbed quite well into the blood stream if the patient takes it with food. The food intake really helps to reduce nausea and this should be encouraged

2.  Avoid spicy foods with the doxycycline. Anything that upsets the stomach has the potential to makes things worse with doxycycline. I generally recommend avoiding spicy foods with doxycycline. 

3. Take Gravol.  If nausea continues despite food intake, dimenhydrate (Gravol) can be used 1 hours before the doxycycline is taken. I generally recommend starting with 25 mg Gravol and then 50 mg and then 100 to see what dose can help reduce the nausea. Gravol can make people drowsy and sleepy so this needs to be considered if one is driving or doing anything that requires focus. 

4. Use Ginger. Ginger is also a helpful anti-nausea treatment. There are a number of candies, lozenges on the market that contain ginger and can be used prior to the patient taking the doxycycline. The company that makes Gravol also has a product "Ginger-Gravol" which can be very helpful. this does not contain Gravol and therefore does not cause drowsiness.

5. Reducing the doxycycline dose. For some users, the nausea is dose related. Reducing the dose can help.

Amphetamines and Hair Loss

Amphetamines are a group of drugs that stimulate the central nervous system. They have been used since the 1920s. Amphetamines are used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy and obesity. At higher doses, amphetamines are also drugs that are frequently abused.

Examples of amphetamines

Most amphetamines are prescription based and include drugs such as:

1.    Dextroamphetamine

2.    Levoamphetamine

3.    Lisdexamfetamine

4.    Methamphetamine

5.    Adderall and Adderall XR

6.    Dexedrine

7.    ProCentra

8.    Ritalin

9.    Concerta

10. Dextrostat

11. Vyvanse

12. Focalin

13. Strattera

14. Zenzedi

15. Evekeo

Hair loss with amphetamines

Hair loss is a possible side effect of amphetamines. It does not happen to everyone but a proportion are affected.  Hair loss typically occurs 4-7 weeks after starting. Daily shedding increases from well under 70 to above 100. Hair loss occurs all over the scalp rather than in any given area. Hair loss from amphetamines can also occur on the body hair.

Hair loss can be from the drug itself or the caloric and nutritional deficiencies that come from the appetite suppressing effect of these drugs.

Evaluation of the patient with suspected amphetamine induced hair loss

It is important for anyone with suspected amphetamine induced hair loss to see a physician. The first step is to determine if the timing of the hair loss and the type of hair loss pattern fit with a diagnosis of amphetamine induced hair loss. On some occasions, the hair loss and amphetamine use is simply a coincidence.  If the amphetamine use is thought to be contributory, it is important to determine if the patient has a telogen effluvium from the actual drug, or from a nutritional deficiency that the drug has brought about or from another cause such as androgenetic alopecia.  Blood tests are necessary for anyone with amphetamine induced hair loss to look for underlying nutritional deficiencies. Sometimes a hair collection or biopsy is also performed.  

Latisse and eye color changes

Can bimatoprost (Latisse) change eye color?

Bimatoprost (Latisse) is a popular product for growing longer lashes. Users of the product are likely very familiar with the fact that the drug was originally used for glaucoma to lower eye pressures. 

The actual drug stimulates pigmentation in the iris because of  the ability of bimatoprost to  increase in pigment granulates in melanocytes. This side effect is mostly observed when individuals put the bimatoprost drops right into the eyes (as is done for those using the medication for glaucoma).

Pigmentation of the iris is not typically observed with those used bimatoprost for the eyelids or eyebrows. However, pigmentation of the surrounding skin can be observed.

Bimatoprost (Latisse) for treating alopecia areata: New study

New study supports use of bimatoprost for alopecia areata 

Bimaprost is FDA approved for treating glaucoma. It's also FDA approved for treating thin eyelashes in those with sparse eyelashes, and in this case is known popularly as Latisse. The use of bimatoprost in treating alopecia areata has only recently been investigated. Studies have suggested a role in treating eyelash loss in those with alopecia areata. 

Bimatoprost in Treating Scalp Loss

A new study, published in Paediatric Dermatology, supports the use of bimatoprost in treating scalp hair loss in patients with alopecia areata. The authors described a 9 year old girl with alopecia areata who had been treated with steroid injections, topical steroids and minoxidil. Despite these treatments, she did not experience regrowth. A decision was made to initiate treatment with bimatoprost solution one drop twice daily on the patches of hair loss. 

Within one month the patient experienced the first signs of regrowth and by 7 months the patient had regrown her hair and was able to stop the bimatoprost. 

Reference

Li and Antaya. Successful Treatment of Pediatric Alopecia Areata of the Scalp Using Topical Bimatoprost. Pediatr Dermatol. 2016

Dutasteride and Finasteride: New data suggests no Link with breast cancer in men

Dutasteride and Finasteride: Do they cause breast cancer?

Finasteride (Propecia) and dutasteride (Avodart) are prescribed for the treatment of male pattern baldness. Many of my male hair transplant patients receive finasteride or dutasteride in order to help reduce the progression of balding in existing hairs.  

Finasteride and dustasteride belong to a group of drugs called "5 alpha reductase inhibitors." They block the enzyme 5 alpha reductase and decrease the levels of the potent androgen hormone DHT (dihidrotestosterone). In addition to reducing DHT, the drugs increase the levels of estrogen slightly which has raised questions from physician and researchers around the world as to whether these drugs increase the risk of breast cancer in men.

US researchers set out to examine the relationship between the use of 5 alpha reductase inhibitors and male breast cancer. They studied men using the higher 5 mg dose of finasteride used in prostate enlargement (rather than the 1 mg dose used in hair loss) and the 0.5 mg dose of dutasteride.  They looked at the use of these drugs in 339 men with breast cancer and 6,780 men without breast cancer.

What were the findings and conclusions from the study?

The authors did not find an association between using 5 alpha reductase inhibitors and the development of breast cancer in men. Overall, the authors concluded that the "development of breast cancer should not influence the prescribing of 5 alpha reductase inhibitor therapy."

Reference

Bird ST et al. Male breast cancer and 5 alpha reductase inhibitors finasteride and dustasteride. J Urology; 190:1811-4