Children of Women with Polycystic Ovarian Syndrome:

What is the latest research ?

Polycystic ovarian syndrome (PCOS) is a hormonal disorder in women. It is not one condition but a constellation of symptoms. Patients with PCOS typically have evidence of hyperandrogegism (excess male type hormones and irregular periods. Women with PCOS typically have cysts present in the ovaries but some do not.  The exact cause of PCOS remains unknown although a genetic component is likely for many women. The ovaries of women with PCOS are known to secrete higher levels of male hormones which contributes to irregular periods and infertility. Women with PCOS may seek medical attention for a variety of reasons including insulin resistance, diabetes, high blood pressure, acne, increased hair growth on the face, irregular periods, infertility.  Women with PCOS may also present to a hair clinic with concerns about androgenetic alopecia. It is therefore extremely important that hair specialists understand this condition. 

New Research on Children born to Mothers with PCOS

A great deal of research is currently being conducted into the cause of PCOS and how it affects women. Research is also being conducted into the health of babies born to mothers with PCOS. Research has suggested that the hormonal changes in utero influence the development of the fetus. 

One issue that has been studied is the risk of attention-deficit/hyperactivity disorder (ADHD) in babies born to mothers with PCOS. ADHD is the most common childhood neurodevelopment disorder. Male hormones may play a role as boys are two to three times more likely to develop ADHD.

A study by Berni and colleagues of over 16,000 women showed that women with PCOS have a slight risk of giving birth to children with attention deficity hyperactivity disorder (ADHD) and Asperger syndrome. 

Kosidou and colleagues performed a matched case-control study using health and population data registers for all children born in Sweden from 1984 to 2008.  In their study, a total of 58,912 ADHD cases (68.8% male) were identified and matched to 499,998 unaffected controls by sex and birth month and year. The results indicated that Maternal PCOS increased the odds of offspring ADHD by 42% after adjustment for confounders (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.26-1.58). The risk for ADHD was even higher among obese mothers with PCOS and was highest among obese mothers with PCOS and other features of metabolic syndrome.

Conclusion

Recent research suggests that differences in maternal hormones during pregnancy in women with PCOS affect the chances of having children with ADHD and possible other neurodevelopmental issues. Overall the risk is low. 

REFERENCES

Berni TR, et al. Polycystic ovary syndrome is associated with adverse mental health and neurodevelopmental outcomes. J Clin Endocrinol Metab. 2018.

Kosidou K, et al. Maternal Polycystic Ovary Syndrome and Risk for Attention-Deficit/Hyperactivity Disorder in the Offspring.  Biol Psychiatry. 2017.

Dermatology and Urology: United by the Androgen Receptor

The Benefits of Urology Research

At first glance, it would seem that the medical specialists of Urology and Dermatology and quite different.  One deals with the physiology and functioning of the urinary system and the other deals with the dermatological system which comprises skin, hair and nails. The two however, are much more closely linked that you might imagine. 

The Androgen Receptor

The Androgen Receptor is a protein that sits in the outer layer of cells (known as the cytoplasm). One of its jobs is to bind to androgens that diffuse into the cell and form an androgen receptor-androgen complex.  The types of androgens that bind to the androgen receptor are many but the most commonly studied ones are testosterone and dihydrotestostone. The newly formed androgen receptor-androgen complex then translocates from the cytoplasm into the deepest regions of the cell (known as the nucleus) where the complex binds to DNA and stimulates the machinery needed for the cell to make new types of proteins (called transcription and translation).

What's the connection?

The androgen receptor has an important role in many fields of medicine including Urology and Dermatology. It's very clear that aberrant signals from the androgen receptor help prostate cancer cells to grow and so an understanding of androgen receptor physiology drives much of the field of prostate cancer research. Some of the drugs that are used to treat prostate cancers are blockers of some kind of androgen receptor function. Common examples are non-steroidal anti androgens like bicalutamide, nilutamide, enzalutamide, apalutamide, and steroidal anti androgens like cyproterone acetate.

In dermatology, the androgens and the androgen receptor also has an important role. Conditions like acne, hair loss and even syndromes associated with increased hair growth can be driven by androgens. Androgenetic alopecia (male balding and female pattern hair loss) are androgen dependent to some degree and medications that block androgens are commonly used. This includes finasteride, dutasteride, spironolactone, cyproterone acetate, flutamide.

Research Research in Urology

I continue to closely follow the field of Urology. There's no doubt in my mind that advances in Urology (especially in prostate cancer research) will directly translate into benefits to dermatology.   Just this week, I was asked about the use of an experimental prostate cancer drug Darolutamide for treating male balding. Darolutamide, which is a close cousin of enzalatumide and apalutamide, is not approved for use yet even for treating prostate cancer but clearly many minds have recognized this important link between drugs in Urology and drugs that may be useful to the hair loss world. 

As yet another example of the commonality between Urology and the field of hair loss dermatology, studies continue to show that balding in the crown (vertex) in men has some link to an increased risk of prostate cancer. Clearly, there are some genes that unite the two conditions, and research into prostate cancer genes and genes for balding will continue to merge together over time. 

Conclusion

It makes good sense for any hair loss specialist to follow the latest happenings in the field of urology. Many urological diseases, especially prostate cancer, are affected by androgens and medications that block the function of androgens provide benefit to these diseases. 

REFERENCE

Liang W, et al. Possible association between androgenic alopecia and risk of prostate cancer and testicular germ cell tumor: a systematic review and meta-analysis. BMC Cancer. 2018.

Jin T, et al. Association between male pattern baldness and prostate disease: A meta-analysis. Urol Oncol. 2018.

Hair Transplants from Another Person?

Can I get a hair transplant from someone else?

In theory, that answer is yes. Theoretically speaking, it would be possible to take hair from another person (the donor) and transplant it to another person (the recipient) and have the receipt use immunosuppressive medications for life in order to keep their hair growing and prevent rejection. However, practically speaking that answer is no. In the current day it is not possible.

Why no?

The incorrect assumption that people make is that immunosuppressive medications are safe. Immunosuppressive medications have very serious side effects and don’t prevent rejection in everyone. Inmunnosuppressive pills affect blood pressure, liver function, cholesterol, mood, blood sugars, bone health, weight, kidney function. They can increase the risk of developing various types of infections and increase the risk of cancer. Organ transplant recipients have shorter life expectancies and a higher risk of dying of both cancer and non–cancer-related causes  These drugs have potentially serious side effects when used to prevent rejection. For that reason, it is not possible.

Interestingly, there are a few rare situations where it would be possible to receive donor hair from another person.  The main one would be a hair transplant in identical twins.  Identical twins have the same genetic material and a hair transplant could be performed without the need for anti-rejection drugs.  

Can I at least try?

Having encountered this question from patients countless numbers of times, I have come to realize that despite the above information, the question often follows -  "can't I at least try?" The short answer is that no, it is not possible to perform a hair transplant using donor hair from another person. In most jurisdictions, it would even be considered malpractice for a physician to even consider performing this procedure in such a situation. However one looks at it, it is not possible and not permitted. 

Someday, it will be possible to produce hair follicles form a variety of sources. Exciting research is currently being conducted that makes things that would otherwise seem impossible - possible.

 

Reference

Source: Rosati P and Bergamo A. Allogenic hair transplant in a bone marrow transplant recipient. Dermatol Surg 1999; 25: 664-5.

Finasteride Use in Women: Yes or No?

Finasteride & Women

Finasteride is FDA and Health Canada approved for men with hair loss. Although it's not formally FDA approved for use in women, the medication has been prescribed to women with androgenetic alopecia for nearly two decades.  When a physician prescribes finasteride for androgenetic alopecia in women, they are said to be using these medications in an 'off label' manner.  The following is the key point about using finasterde for women : it's only prescribed on a case by case basis. 

Polar Views on Finasteride Use

The public needs to understand there are many views among physicians  on finasteride. There are some physicians that will never prescribe this medication to women -  period.  There are some physicians who will prescribe it only to post-menopausal women. There are some who will prescribe to some pre-menopausal and some post-menopausal women - but only on a case by case basis - and only with full counselling of risks and benefits.   

Much of the concern around use of finasteride in pre-menopausal women stems from the significant harm that would come to any fetus that was born to to a mother who used finasteride during pregnancy. These risks and real - and serious. Finasteride is given the highest category of risk during pregnancy - so called "category X." Women who are pregnant or who could become pregnant must never use finasteride.

The other concern that some physicians have pertains to cancer risk. To date, we actually don't have any good evidence to suggest that finasteride increases a woman's risk of cancer. In fact, reasonably well conducted studies in men would suggest that breast cancer risk is not increased. Good studies have not been done in women. However, women with strong histories of estrogen dependent cancers (breast, ovarian, gynaecological cancers) should also review use of finasteride with their doctors.  In some cases, use may not be appropriate.  I'll discuss other side effects below. 

 

Does Finasteride Help Genetic Hair Loss in Women?

So does it help women with genetic hair loss? Studies from nearly two decades ago said no. A study by Dr vera Price and colleagues in 2000 suggested a 1 mg dose in post menopausal women did not help androgenetic alopecia.  But just 2 years later, in 2002, Shum and colleagues presented 4 women (2 pre and 2 post menopausal) who did respond to a higher dose of finasteride - this time 2.5 mg finasteride. All 4 women had hyperandrogenism (one or more of elevated hormones, hair on the face, infertility issues). This refueled interest in the role of finasteride for women. 

In 2006, Dr Iorizzo and colleagues from Bologna, Italy published a study which further renewed interest in the use of finasteride for the treatment of female pattern hair loss. Iorizzo and colleagues looked at the benefit of finasteride at a dose of 2.5 mg in 37 women diagnosed with female pattern hair loss. All women in the study were also using a birth control pill to prevent pregnancy.  After 12 months of follow up, 62 % of women using finasteride had an improvement in hair density. 13 patients (30 %) hair loss had stabilized -   it did not get worse but  did not improve. Only 1 of 37 patients experienced a worsening of their hair density.
 

What are the side effects of finasteride in women?

I'm often asked about the range of side effects that are possible for women who use finasteride. Side effects of finasteride in women include, but are not limited to: harm to a fetus (finasteride can not be used in pregnancy), fatigue, weight gain, depression, anxiety, decreased libido, sexual dysfunction, hair shedding, breast tenderness, breast enlargement.  Other side effects can occur but are less common. These include changes in platelet counts and muscle injury (myopathy).

Reference

Iorizzo M1, Vincenzi C, Voudouris S, Piraccini BM, Tosti A. Finasteride treatment of female pattern hair loss. Arch Dermatol. 2006.

Shum et al. Hair loss in women with hyperandrogenism: Four cases responding to finasteride. Journal of the American Academy of Dermatology 2002; 47: 733-9

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

Preventing Androgenetic Alopecia: Is it possible?

Preventing AGA in Men and Women

I'm often asked if one can prevent genetic hair loss. The typical scenario is a patient whose parent or sibling is bald or balding and wants to know if they can reduce their chances of developing a similar pattern of hair loss. Can one prevent balding outright? In the present day, that answer is no. However, there are things that can be done to reduce the magnitude and speed of progression of the hair loss.

Genetic Hair Loss is strongly ... genetic. It's the genes inside the hair follicles that influence how the hair loss will or will not unfold. We'll take a look at factors that can affect genetic hair loss to a slight degree in a moment, but first let's turn our attention to studies of identical twins. 

Studies of identical twins are very important in answering questions like "does what I eat affect my rate of balding?" or ,,,, "does being stressed affect how fast I bald?"

Identical twins carry the same genetic profile. By studying the appearance of identical twins at various points throughout their lives, we can get a better sense of how important factors like genetics and the environment actually are. If genes are the "key factor" in how balding progresses then, identical twins should look ‘identical’ in terms of their hair density at various points in their lives. In contrast, if environmental factors like smoking, drinking, stress, weight loss and ultraviolet radiation are important, identical twins might not have the same hair density because their environment is different. 

The 1992 Hayakawa Study

Interesting research studies in 1992 showed that genetics is by far the most important factor and the environment only has a minor role. 92 % of identical twins were found to have "no significant" differences in their hair density at later points in their lives. However,  8% of identical twins had a slight difference. Interestingly, no twin had a striking difference! In other words, there was never a situation where one identical twin was bald and another had full hair. These studies support the notion that one’s genetics is by far the most important factor in the balding process - but there is a slight role for how outside 'environmental factors' shape genetic hair loss.

Limiting Genetic Hair Loss: Optimizing Environmental Factors  

The Hayakawa studies taught us that there is a bit of room to optimize how fast genetic hair loss occurs. Overall, these factors have a minor role but still have some role. These factors include the following.

1) Be a non smoker.

It's clear that smoking can influence genetic hair loss by speeding up how fast it progresses. An important study examing the relationship between smoking and hair loss was a 2007 study by the Taiwanese group of Dr. Su and Dr Chen.  These researchers examined 740 patients between the ages of 40 and 91 over a 2 month period.  They found that smokers generally had worse androgenetic alopecia compared to non-smokers. In fact, smokers had nearly a two-fold increased risk of having moderate or severe genetic hair loss compared to non-smokers. In addition, the early development of male balding was more likely in smokers. The exact reasons is not clear but it has been proposed that smoking is damaging to the tiny blood vessels and the there are toxic substances in cigarette smoke that damage the cells in the hair follicles. It's also possible that smoking causes inflammation which speeds up the process of genetic hair loss. 

2) Keep a healthy weight. 

It does appear that obesity increases one's risk of developing worsening androgenetic alopecia. A 2011 study looked at the risk factors for male balding in policeman in Taiwan. Interestingly, young male policemen who were obese had much higher rates of male balding than thinner policemen. In 2014, researchers from Taiwan explored whether there was a relationship between obesity the severity of male balding. They studied 142 men (average at 31 years) with male balding who were not using hair loss medications.   The study showed that men with more severe  hair loss tended to be more overweight than men with less severe hair loss.  In fact, men who were overweight or obese had an approximately 3.5 fold greater risk for severe hair loss than men with more normal weights. In addition, young overweight or obese men had a nearly 5 fold increased risk of severe hair loss. The exact reasons are unclear. However, obesity leads to altered metabolism, insulin resistance and worsening inflammation that could affect balding. 

 

3) Limit anabolic steroid use.

Anabolic steroids can worsen genetic hair loss in those that are predisposed. These steroids increase the pool of androgens that all act to facilitate miniaturization.

4) Reduce ultraviolet radiation to the scalp.

An interesting study from researchers in Taiwan offers further clues that sunlight just 'might' contribute in some way to male balding.  The researchers compared balding patterns in 758 policemen  and 740 men in the general polulation.  Interestingly, policemen aged 40 to 59 had a two fold increased risk of having male balding. In addition, there was a statistically significant association between male balding and sunlight exposure. More research is needed understand if and how ultraviolet radiation affects the process of male balding. Reference

 

Conclusion

It's not always possible to prevent genetic hair loss. However, it may be possible to reduce the speed of its progression by limiting hair shedding and limiting toxic (i.e. smoking, obesity, UV radiation) and hormonal effects (i.e. anabolic steroids) on the hair follicle.

Reference

Hayakawa K, et al. Intrapair differences of physical aging and longevity in identical twins. Acta Genet Med Gemellol (Roma). 1992.

Su LH and Chen T H-H. Association of Androgenetic Alopecia with Smoking and Its Prevalance Among Asian Men. Archives of Dermatology 2007 143; 1401-1406.

Mosley JG and Gibbs AC. Premature grey hair and hair loss among smokers: a new opportunity for heatlh education? British Medical Journal 1996; 313: 1616.

Severi G et al Androgenetic alopecia in men 40-69 years: prevalence and risk factors.British Journal of Dermatology 2003; 149: 1207-1213

Chao-Chun Y et al. Higher body mass index is associated with greater severity of alopecia in men with male-pattern androgenetic alopecia in Taiwan: A cross-sectional study.  J Am Acad Dermatol 2014; 70; 297-302.

Su LH et al. Androgenetic alopecia in policemen: higher prevalence and different risk factors relative to the general population (KCIS no. 23). Arch Dermatol Res. 2011 Dec;303(10):753-61

Spironolactone for Female Androgenetic Alopecia (AGA)

Spironolactone for Female Genetic Hair Loss

Spironolactone has been used off label in the treatment of androgenetic alopecia (also known as female pattern hair loss, FPHL) for approximately two decades.  The medication acts to reduce the effects of androgens in several ways.   It reduces adrenal androgen production and exerts competitive blockade on androgen receptors. 

Although there are yet to be any randomized placebo controlled trials examining the benefits of Spironolactone in FPHL,  case reports, series, and an open-label trial support its benefit. In a small case study, 200 mg spironolactone reduced hair loss by 50%–62.9% and also increased the total number of anagen hairs.  Perhaps the most important study to date was an an open-label study of 80 women with biopsy-proven FPHL who either received spironolactone (200 mg daily) or cyproterone acetate (either 50 mg daily or 100 mg for 10 days per month if premeno- pausal) for at least 12 months. This study showed that 44% of patients experienced visible hair growth (improvement), 44 % had their hair loss stopped. Only 12 % had reduced hair density. Another key finding of this particular study was that benefits did not depend on whether women had high androgens or normal androgens.  Other studies have shown that adding minoxidil to a spironolactone based treatment plan can be additive and some patients will achieve even further benefits. 

Readers may find these links helpful. The pertain to other articles written by Dr. Donovan on Spironolactone:

Spironolactone for FPHL - A UCLA Study

Irregular Periods from Spironolactone

Spironolactone for FPHL

Hormone Levels and Spironolactone Use: Does it matter?

Should one start Spironolactone with Minoxidil?

 REFERENCE

Sinclair R et al. Treatment of female pattern hair loss with oral anti androgens. Br J Dermatol 2005

Is topical finasteride completely free of side effects?

Topical finasteride is lower risk

Finasteride is a medication which blocks an enzyme known as 5 alpha reductase. It reduces DHT levels. Some of the side effects that are possible come from this reduction in DHT in the blood stream.  These include mood changes, sexual dysfunction, weight gain. In effort to reduce the risk of side effects there are increasing efforts around the world to create topical finasteride. Some of it is made up by compounding pharmacies. In some countries, it is commercially available (as in MorrF in India (Intas Pharmaceuticals).  

Topical Finasteride Gets Absorbed and Reduces Serum DHT

It's important for any user of topical finasteride to be aware that there is some small degree of absorption of finasteride into the blood stream even with topical finasteride. Studies have shown that the amount is low but one needs to keep in mind that if an individual is extremely sensitive to small fluctuations in serum DHT, this could still be relevant. 

Studies have suggested that with some formulations of topical finasteride about 1/10th to 1/20th of the amount gets absorbed into the blood compared tot he amount if the pills were used.  Studies have shown that topical finasteride still reduces serum DHT. Instead of reducing DHT by 70 % (as in the case of the pills), DHT is still reduced 25 %. Of course the degree of reduction is not the same as oral finasteride but nevertheless topical finasteride does reduce serum DHT.

 

Conclusion

I am not of the opinion that topical finasteride thas zero side effects. However, I am of the opinion that the chances of side effects are very low and significantly lower that oral finasteride. However, we still don't know if topical finasteride works quite as well as oral finasteride. Those "good" studies have not been done despite the rapid increase in world wide use of topical finasteride.  One must always keep in mind that there is no such thing as "standard" topical finasteride. Some pharmacies compound finasteride that can easily get into the blood stream and yet others use other chemicals in the formulation that make it more difficult for the finasteride to enter the blood stream. A variety of chemical constituents, including so called "liposomes", make it more difficult for finasteride to enter the blood all the while providing benefit in the scalp (and to the hair loss).  I always tell my patients that the topical finasteride they buy at their pharmacy may not be the same as another person buys at their pharmacy. We need to stop referring to this group of medications by the general term topical finasteride and referring to it by the specific formulation (i.e. 1% liposomal finasteride, or 0.1 % finasteride in soy phosphatidylcholine, ethanol, water). There is no such thing as standard topical fiansteride.

Gynecomastia in Finasteride Users: The Basics

What is Gynecomastia?

Gynecomastia refers to the enlargement of breast tissue in men.  It's extremely common and throughout life, a majority of men will be affected. For some, it will occur during infancy or puberty and resolve. For others it will start in puberty and persist and for others it will occur in older ages.

Gynecomastia by Age

Gyneomastia is common in newborns. Due to estrogens from the mother, 60-90% of male babies have enlarged swollen breast tissue. It resolves in a matter of weeks for most. For young male adolescents, gynecomastia is embarrassing but common. It can start at age 10-12 but typically it starts around 13 or 14 years of age.  About 50 % of male adolescents may be affected.  The breast swelling goes away on its own in 6 months to 2-3 years. In 20 % of affected teens, the swelling persists into adulthood. In men, gynecomastia is present in men 20-40, but particularly peaks in incidence after age 50. In the 50 plus age group, about 25-30 % of men are affected.  The number may rises to well over 50 % in 60 + age groups.

What causes gynecomastia?

Gynecomastia is caused by a variety of factors including genetics, drugs and physiological causes. Regardless of the precise cause, it is though that some hormonal imbalance (especially favouring estrogen and increasing the estrogen to androgen ratio) triggers breast tissue enlargement.  The actual level of hormones in the blood stream is typically normal and it's the ratio of these drugs at the actual level of the breast tissue itself that is important. Drugs cause about 10-25 % of cases. Pubertal gynecomastia that persists into adulthood is responsible for another 25 % of cases. The causes is generally unknown in about 25 % of cases as well.  But the list of potential causes is long and a full review is needed for anyone with concerns about gynecomastia. A variety of genetic syndromes (i.e. Klinefelter syndrome), metabolic problems, cancers all reduce the bodies production of testosterone and increase the estrogen to androgen ratio.

 

Drugs causing Gynecomastia

For hair specialists, it's well know that finasteride is among the causes of gyneocmastia. About 4 to 10 out of every 1000 men using finasteride will develop gynecomastia on account of the drug. But a variety of other medications and products can cause gynecomastia including:

1. Anti-androgens. (Finasteride Dutasteride). This anti-androgens is commonly used for treating male pattern balding. 

2. Anti-androgens. (Spironolactone). This anti-androgens is typically used for women with hair loss but not typically for men. 

3. Ketoconazole (anti-fungal). Generally speaking the risks is greatest with oral ketocoanzole rather than topical products. Oral ketoconazole is rarely used nowadays in North American due to safer anti-fungal agents. 

4. Heart burn medications (H2-receptor blockers). Drugs used to treat ulcers and heart burn including Cimetidine has the greatest evidence as a drug of this class being implicated. The others less so.

5. Tea tree oil and lavender oils. These essential oils have been reported to increase the risk of gynecomastia in children. Tee tree and lavender are found in soaps, shampoos and lotions. 

6. Other drugs. A variety of other drugs may also be implicated. A 2012 review classified drugs into two main groups including those 'definitely associated with gynecomastia" and those "probably associated with gynecomastia." The first group (drugs definitely associated with the onset of gynecomastia) inlcuded spironolactone, cimetidine, ketoconazole, hGH, estrogens, hCG, anti-androgens, GnRH analogs and 5-α reductase inhibitors.  The second group of drugs "probably associated with gynecomastia" include risperidone, verapamil, nifedipine, omeprazole, alkylating agents, HIV medications (efavirenz), anabolic steroids, alcohol and opioids.

Finasteride Induced Gynecomastia

Finasteride is FDA approved for treating male balding at a dose of 1 mg daily. It is among the medications known to cause  gynecomastia. The risk is likely about 4 to 10 out of every 1,000 users. Finasteride induced gynecomastia is often one-sided but can be both sides. This is especially true at lower doses like 1 mg compared to 5 mg. Finasteride induced gynecomastia can start as early as a 1-2 weeks after staring the drug but is typically a few months delay. It can also be 1-2 years before the phenomenon is appreciated. Pain is not uncommon in men with finasteride induced gynecomastia - and this pain/tenderness can occur prior to any actual enlargement. The 1 mg dose is less likely than the 5 mg dose to cause breast enlargement in men. Finasteride induced gynecomastia can reverse completely in many individuals provided the drug is completely stopped in the early stages when the breast enlargement is noted. If the drug is not stopped, it can enter a irreversible stage (where only surgical treatment will provide treatment). Finasteride induced gynecomastia is more likely in obese indivdiuals and with advanced age. Most of the time blood tests and various hormonal tests are normal in men with finasteride - induced gynecomastia. 

 

Treatment: How is gynecomastia treated?

The treatment of gynecomastia depends on the precise causes. For most adolescents, a conservative (watch and wait) approach is usually taken as the condition usually resolves in most cases. Only 20 % of adolescent cases of gynecomastia persist into adulthood.  Medical treatments are usually not effective. However, in some hormonal abnormalities, medications such as aromatase inhibitors can be used.  Usually surgery is needed to remove the excess tissue if that is what is so desired by the patient.

REFERENCES

Rodriguez et al.  Risk of gynaecomastia associated with cimetidine, omeprazole, and other antiulcer drugs. BMJ. 1994 Feb 19; 308(6927): 503–506. 

Bera F, et al. [Impotence and gynecomastia secondary to hyperprolactinemia induced by ranitidine].Therapie. 1994 Jul-Aug.

Deepinder F, et al. Drug-induced gynecomastia: an evidence-based review. Review article. Expert Opin Drug Saf. 2012.

Fentiman IS, et al. Managing Male Mammary Maladies. Eur J Breast Health. 2018.

Soliman AT, et al.  Management of Adolescent Gynecomastia: An Update.Acta Biomed. 2017

Using Finasteride with Pre-existing Gynecomastia

Does finasteride make gynecomastia worse?

I'm often asked if finasteride could make gynecomastia worse if one has gynecomastia to begin with.  The short answer is that it could. There are a large number of  anecdotal reports of finasteride worsening pre-existing gynecomastia. The challenge in giving good hard facts to the question is that a good clinical trial has not been done in men who have gynecomastia and start finasteride. 

Most studies have looked at the risk of gynecomastia in men starting finasteride who don’t have gynecomastia to begin with. Most men with gynecomastia to begin with are excluded from these trials so we don’t have good data on how gynecomastia worsens in finasteride users. Finasteride raises estrogen levels and it would make sense from a mechanistic and pathophysiological point of view that that small increase in estrogen could trigger hyperplasia of breast tissue in susceptible men. I encourage all males with concerns about gynecomastia to discuss these issues with their physicians. Serial photography of breast tissue is essential although frequently not done.

Birth Control Pills, Hormones and Hair Loss: Important Considerations

Birth Control Pills affect Androgens

Oral contraceptives have many effects on the hair.  For some  women, oral contraceptives can cause hair shedding when started or stopped by triggering a telogen effluvium. Fortunately for most, this shedding is temporary.  Oral contraceptives can also benefit the hair in many women with androgenetic alopecia by reducing the levels of androgens (male type hormones) in the blood.

Where do androgens come from? 

There are three important sources of androgens in women.  About 50 % of testosterone in the blood comes from the conversion of hormones such as androstenedione and dehydroepiandrosterone (DHEA) and its sulphate dehydroepiandrosterone sulphate (DHEA-S). About 25 % of testosterone comes form the adrenal gland and 25 % from the ovary. 

About 65 % of testosterone that circulates in the blood stream gets bound and inactivated by sex-hormone-binding globulin (SHBG). Most of the remaining 30–35% is bound by albumin. Only 0.5–3% represents freely circulating T ("free T"). Despite the low amount, free T is important as it is active and able to cause a range of clinical phenomena such as hair loss acne and increased hair growth on the face (hirsutism).

Effects of Oral Contraceptives Pills on Androgens

Oral contraceptives (birth control pills), particular the combined oral contraceptives (COCs) are known the levels of androgens in the blood including testosterone, androstenedione and DHEAS. For example, blood levels of testosterone decrease by as much as 50 %. This occurs from the ability of oral contraceptive pills to a) reduce androgen synthesis in the ovary b) reduce androgen synthesis in the adrenal gland and c) increase sex hormone binding globulin in the liver. 

Because of their effects on androgens, birth control pills are options for women with certain types of hair loss, including androgenetic alopecia associated with normal hormone levels, and androgenetic alopecia associated with polycystic ovarian syndrome (PCOS).  Birth control pills are not appropriate for everyone with these hair loss conditions and anyone considering these medications should carefully review risks and benefits with a physician.

Female Pattern Hair Loss

Major and Minor Criteria

Female androgenetic alopecia is common. By the age of 50, well over 1/3 of women will have androgenetic alopecia (AGA)- also known as female pattern hair loss (FPHL). This type of hair loss causes thinning in the frontal and mid scalp. The sides and back may also be affected but generally to lesser degrees than the front for most women. Traditionally, the diagnosis of androgenetic alopecia has been made based on the finding of reduced density in the frontal scalp compared to the back of the scalp and the clear demonstration via dermoscopy that there is a variation in the diameter if more than 20% of hair follicles. This is known as anisotrichosis.

In 2009, Dr Rudnicka and colleagues proposed a series of major and minor criteria for diagnosing FPHL.

FPHL MAJOR CRITERIA

(1) ratio of more than four empty follicles in four images (at 70-fold magnification) in the frontal area

(2) lower average thickness in the frontal area compared to the occiput

(3) more than 10% of thin hairs (<0.03 mm in diameter) in the frontal area.

 

FPHL MINOR CRITERIA

(1) increased frontal to occipital ratio of single-hair pilosebaceous units

(2) vellus hairs

(3) peripilar signs.

Remarkably, the presence of two major criteria or of one major and two minor criteria allow diagnosis FPHL with 98% specificity.

 

Reference

Rakowska A et al. Int J Trichol. 2009;1:123–30.

Hair Transplants in Young Men

Are hair transplants an option under 25?

Hair transplantation is rarely a good option in men under 25 and it's generally never an option for men in the early 20s (i.e. before age 23). I completely understand that hair transplants are performed around the world in young men age 18-22. However, I don't think it's a good idea.

 

Why hair transplants in young men is not advisable

In an effort to look better and do something positive, many men rush into hair transplants. Not a day goes by that I don't see it or hear it.  There are a number of things that all young men should keep in mind.

 

1. Hair loss does not stop - it continues forever

Too many young men forget that hair loss will continue forever. If a patient is developing genetic hair loss at a young age, one thing is for sure: they will continue to slowly bald unless medication treatment is considered.  Having a hair transplant does not stop the balding process - it only delays the appearance.

2. Males who start balding in the early 20s are likely to develop advanced balding patterns in their 30s and 40s. 

It is critically important to understand that once genetic hair loss starts, it will continue forever. If balding starts at a young age, there is a very high chance that male will develop more significant hair loss in the 30s, 40s or 50s.  

3. Males who have hair transplants in the early 20s must be prepared for more surgeries throughout their lifetime

If a hair transplant is performed in the frontal hairline at too young of an age, the hairs that are moved into the frontal hairline may last a long time. However, the hairs 'behind' this frontal area could potentially disappear as normal balding continues along its course. At hair transplant performed at too young of an age often leads to placement of place hairs in an area which could look unnatural in the future. A good example would be the placement of too low of a hairline or a hairline with not enough curve to it.  In order for the patient to continue to look good and not have a 'gap' develop between the transplanted hairs and the continually receding hairline, the patient must return to the surgery centre from time to time for more transplants. In other words, if needs to be prepared for a lifetime of hair transplants. Therefore, a hair transplant is not a one time thing.

4. It's nearly impossible to predict prior to the mid 20s how many donor hairs a patient actually has. 

If humans had an infinite number of hairs in the “donor” area to move through hair transplants, I would be more likely to advise that more young men move forward and have hair transplants. However, hair in the donor area at the back of the scalp is present in limited supply. A young male with balding may have anywhere from 0 hairs to move (if they have diffuse unpatterned alopecia or DUPA) to up to 8000 folllicular units to move in his lifetime. It may not be clear until the mid to late 20s whether the number is closer to zero or closer to 8000.

Before the mid 20s, one needs to keep in mind that it is just a 'guess' as to how best to use hair transplant grafts from the back of the scalp.  As one ages, it becomes much clearer as to where it is best to place these grafts.  

Conclusion

It's rarely a good idea for a young man to have a hair transplant before the mid 20s. There are exceptions whereby a hair transplant in a 23 or 24 year old can be life altering - but these are rare exceptions. In most cases, I recommend these young patients strongly consider non surgical treatments to try to stop their hair loss before considering hair transplantation.

Treatment of Androgenetic Alopecia During Pregnancy

Treating AGA in Pregnancy:

Most treatments for AGA are either not safe or not recommended during pregnancy. This includes minoxidil, anti androgens, various supplements, over the counter products and topical agents. The cardinal rule of treating any conditions during pregnancy or using any treatment during pregnancy is simple: ask a physician. 

Low Level Laser: Generally Safe for Most

 Low level laser treatments (LLLT) are the only safe treatments during pregnancy for women with AGA. This applies to most of the standard at home devices. Everything else needs stopping and some treatments need stopping well in advance. For some women, treatments during pregnancy are not necessary because it is possible due to hormonal surges during pregnancy stopping treatment may potentially not have a huge effect while pregnant and one can start many treatment again after giving birth. However, it should be noted that some women do experience hair loss during pregnancy as well.

WHICH HAIR LOSS MEDICATIONS ARE SAFE TO USE WHILE BREASTFEEDING?

Although I often ask my patients to discontinue most hair loss medications during pregnancy, the question frequently arises as to whether some medications can be restarted while moms are breastfeeding.  Breastfeeding has many benefits for babies.  For some drugs, the answer is yes. For others, the answer is no.

In 2001, the American Academy of Pediatrics published a helpful guide as to the safety of medications during breastfeeding. It's important to always check with your physician before starting any medication during breastfeeding. However, the following medications (used in hair loss) are felt to be safe for women who are breastfeeding.  For a full list of medications which are safe during breastfeeding, click here.

I generally do not recommend restarting treatments until month 1 after delivery if the baby is breastfed although many studies and reports show no harm in use if minoxidil and antiandrogens by women who are breastfeeding.

Focal Atrichia in AGA

Focal atrichia: What does it mean? 

Focal atrichia refers to small circular areas on the scalp that are devoid of hair. These areas are typically slightly larger than a pencil eraser. 

Focal atrichia is seen in both male and female androgenetic alopecia and more common in more advanced stages. They may contain a few tiny vellus hairs if one looks closely but eventually these tiny hairs disappear over time. Hair regrowth does not occur in these areas.

Studies by Olsen and Whiting (see references below) showed that focal atrichia was present in 44% of women with female pattern hair loss, including 67% of late onset vs 15% of early onset, compared to 3/146 (2%) of those with other hair disorders. Hu and colleagues showed that focal atrichia in men with balding was associated with more advanced stages.
 

Reference

Olsen EA, et al. Focal Atrichia: A Diagnostic Clue in Female Pattern Hair Loss. J Am Acad Dermatol. 2017.

Hu R, et al. Trichoscopic findings of androgenetic alopecia and their association with disease severity. J Dermatol. 2015.

Does Finasteride Help All Causes of Hair Loss?

Finasteride: FDA approved for Male Balding

Finasteride is FDA approved for androgenetic alopecia in males but may also help hair loss from other conditions.

Finasteride for Male Balding

Finasteride was approved in 1997 for male balding at a dose of 1 mg. This approval came 5 years after finasteride was approved for treating prostate enlargement at a dose of 5 mg. Although generics are now available, the finasteride pills was initially marketed only as Propecia. For males with balding, it helps all areas that are thinning with the crown helped somewhat more than the front. Young males under 40 seems to get more benefit in the frontal areas of hair loss than men over 40.  Side effects of finasteride should always be reviewed before starting. 

Finasteride Side Effects - Donovan Hair Clinic

What conditions does finasteride help?

Finasteride is approve for male balding but may help several other conditions. These conditions include frontal fibrosing alopecia, some types of female patterned hair loss and very rare cases of lichen planopilaris including fibrosing alopecia in a pattern distribution (FAPD). Such uses are "off-label" and prescribed only in select cases.

What conditions does finasteride not help?

Finasteride does not help other types of hair loss. It does not appear to have benefit in alopecia areata, trichotillomania, telogen effluvium,  infectious causes of hair loss, and scarring alopecias such as folliculitis decalvans.  

Hair loss is not a guessing game.

Guessing is easiest for men's hair loss

If you had to "guess" the reason for someone's hair loss, you'd likely guess correctly if the patient was male and you chose male balding (androgenetic alopecia). By far that's the most common cause of balding in men.  Dozens of other causes are possible, but they are not common. 

Hair loss in women is more complex.

For women, there's a very good chance you'd be wrong if you guessed androgenetic alopecia as the sole cause. Female hair loss is far more complex - and hair shedding issues and even scarring conditions are not uncommon. Hair loss of course, is not a guessing game and a diagnosis can usually be made by the patient's history, examining the scalp and sometimes examining blood test results or (rarely) performing a scalp biopsy.

HOW ARE HAIR FOLLICLES ARRANGED?

Follicle arrangements

Hair follicles normally emerge from the scalp in groups of 1, 2 or 3 haired "bundles." They don't all emerge as single strands.

During the process of genetic hair loss as well as during the process of scarring alopecias, the bundles of 2 and 3 haired follicular units start disappearing from the scalp and what is left is 1 and 2 haired follicular units.

DHT LEVELS AND FINASTERIDE

How do DHT levels change with one dose of finasteride?

Understanding how DHT levels change with finasteride is important in order to best counsel patients - especially those experiencing side effects. 

After taking 1 pills of finasteride, the drug itself is largely eliminated from the body in 1-2 days given that the half life of finasteride is about 4-6 hours (after five half lives a drug is significantly reduced in the body). However the same is not true of DHT levels. After a single dose of finasteride, DHT levels are reduced by 60 % (ie from 65 ng/dL to 25 ng/dL). However, the DHT levels don't rise back up quickly even though the drug is out of the body. Rather, DHT levels rise slowly increasingly just 15-20 % after the second day (ie from 25-30 ng/dL up to 30-35 ng/dL). Now back to the original question.

Of the two lines in the diagram, red or yellow, which best depicts how finasteride levels change with a single pill?

The answer is the yellow line! This concept is important since patients who are experiencing finasteride related side effects may still benefit from dosing every second or third day. It may not be quite as effective but as we can see from the graph, DHT levels are still being suppressed by this dosing schedule.
 

Reference

Vermeulen et al. Eur Urol 1991.

Is it okay to use more minoxidil?

Using more minoxidil is not advised

The dosings of medications have been carefully worked out to balance efficacy with safety. If a patient feels he or she needs more, they should speak to their physician or pharmacist regarding how to apply minoxidil efficiently. If one feels this dose does not work, they might consider a variety of off label means... but only under supervision. This could include using a bit more than 1 mL, or using oral minoxidil at low doses.

Side effects of using too much minoxidil

The side effects of overdosing on minoxidil include worsening headaches, dizzininess, low blood pressure, heart palpitations, heart rhythm disturbances, ankle swelling, hair growth on the body. Rarely patients end up in the emergency department every year because they feel so unwell after using too much minoxidil. 

Minoxidil is a drug and use must be respected.

Minoxidil: Does age really matter?

Minoxidil and age-related hair loss

Minoxidil is a topical medication used to treat many forms of hair loss including androgenetic alopecia (for which it is FDA approved). Minoxidil can be helpful for treating androgenetic alopecia at any age but becomes even more important to consider with advancing age. 

Senescent alopecia: A type of hair loss often forgotten

Hair thinning as one approaches the 60s and 70s is often less truly androgen driven. The diagnosis of senescent alopecia (SA) needs to be considered in these particular age groups and it can often respond to minoxidil. Senescent or age related alopecia is often forgotten by physicians. It mimics genetic hair loss almost perfectly so is easily misdiagnosed as genetic hair loss. The genes driving it are very different. The key point is that if one recognizes senescent alopecia could be a possibility - the use of treatments like minoxidil become more important rather than other traditional AGA-type treatments like finasteride.

Androgenetic alopecia tends to start somewhere between age 8 and age 50. Hair thinning that occurs later has a high likelihood of representing senescent alopecia. (Of course other types of hair loss may also occur after age 60 and genetic hair loss and senescent alopecia can overlap). A study by Karnik and colleagues in 2013 confirmed that these two conditions (AGA and SA) are truly unique. The authors studies 1200 genes in AGA and 1360 in SA and compared these to controls. Of these, 442 genes were unique to AGA, 602 genes were unique to SA and 758 genes were common to both AGA and SA. The genes that were unique to AGA included those that contribute to hair follicle development, morphology and cycling. In contrast to androgenetic alopecia, many of the genes expressed in senescent alopecia have a role in skin and epidermal development, keratinocyte proliferation, differentiation and cell cycle regulation. In addition, the authors showed that a number of transcription factors and growth factors are significantly decreased in SA. The concept of senescent alopecia is still open to some debate amongst experts. The studies by Karnik give credence to the unique position of these two conditions. But studies by Whiting suggested that it is not so simple as to say anyone with new thinning after age 60 has SA - many of these are also more in keeping with androgenetic alopecia. As one ages into the 70's, 80's and 90's - hair loss in the form of true senescent alopecia becomes more likely.

Reference

Karnik et al. Microarray analysis of androgenetic and senescent alopecia: comparison of gene expression shows two distinct profiles. J Dermatol Sci. 2013.