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Aggressive telogen effluvium in males: A common misdiagnosis of androgenetic alopecia

Question

I am a 23 year old male and have been diagnosed with fairly aggressive case of telogen effluvium. It started at age 21 and does not seem to be improving. I have been using biotin supplements recently but they too don’t seem to be helping. I am healthy and take no medications or drugs. What are your recommendations to stop the shedding?

Answer



Thanks for the great question. I think the most important consideration for you is whether, in fact, you have been given the correct diagnosis. I would need to see photos and know everything about your story and recent blood test results to tell you what diagnosis you have. However, androgenetic alopecia (male balding) needs to be considered in your case. In fact, I would state it even more boldly: in a situation like this with a 2 year history of hair loss in a 23 year old male, we need to prove that you don’t have androgenetic alopecia before moving any further. Once we deal with that, we can move on.

Far too many cases I see that are diagnosed as being telogen effluvium are misdiagnoses. Does telogen effluvium exist? Of course! In fact it is a common cause of shedding in patients with hair loss. Is 2 years of telogen effluvium common in a 23 year old healthy male? No, it most certainly is not.


Telogen effluvium happens from a variety of reasons. These include low iron levels, thyroid problems, stress, medications and illness. In most cases, they are temporary and once the trigger is identified and stopped or fixed- hair grows back. In your case we need to look for a trigger but the reality is that after two years of shedding in a healthy male, there may not be one. It’s still important to search.

Most cases of aggressive telogen effluvium in young males are in fact cases of aggressive androgenetic alopecia instead. It is commonly forgotten that androgenetic alopecia in males can be associated with shedding. In young males with strong genetics that is driving the balding process, shedding can be quite significant.

A male with shedding needs of course to have a full evaluation. One needs to know your history in precise detail. Underlying health conditions, medications, recreational drugs, sexual transmitted diseases, diet, eating disorders and psychological issues all need to be considered.

Young males with shedding need blood tests for CBC, iron (ferritin), thyroid (TSH) and vitamin D (25 hydroxyvitamin D). A hormonal profile is not useful for most males. Other tests could be relevant on a case by case basis including zinc, ANA, ESR and tests for sexually transmitted diseases but usually these are unnecessary.

If there is any doubt that exists, a scalp biopsy can be helpful in proving or disproving whether a patient has androgenetic alopecia - especially when so called “horizontal sections” are used by the pathology lab. Horizontal sections allow the pathologist to determine accurately something called the terminal to vellus (T:V) ratio. A terminal to vellus ratio of less than 4:1 indicates a high likelihood of androgenetic alopecia.

In summary, for a young male a diagnosis of “aggressive telogen effluvium” one must be absolutely certain that a diagnosis of androgenetic alopecia is not being missed.

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Minoxidil Itching: What are the important considerations and actions?

Question:

Is it possible that patients using minoxidil get itching because of the minoxidil and that this itching in turn causes more hair loss. I have tried both foam as well as liquid form, but still get itching. Can you tell me a prescription for minoxidil compounded in glycerin, water and ethanol.

Do you have any suggestions?

Answer

Thanks for the excellent question. Itching is often experienced by users of minoxidil. An accurate diagnosis of the precise cause of the itching is important for anyone because there are actually many causes of itching in minoxidil users. The top three considerations for you and your physicians to sort out are 1) Is minoxidil worsening an underlying seborrheic dermatitis? 2) Am I allergic or irritated by minoxidil? 3) Do I actually have another itching diagnosis that has been missed?

1) Is minoxidil worsening an underlying seborrheic dermatitis?


We’ll begin by talking about seborrheic dermatitis. This is a common condition and minoxidil can make it worse for some users. For patients with itching associated with minoxidil use, one needs a full review by their physician. I often advise patients to shampoo daily and add a few anti-dandruff shampoos to their routines. Ketconazole shampoo on Monday, Zinc pyrithione shampoo Tuesday and selenium sulphide Wednesday and then repeat. These should be applied for 60 seconds each application. Often the itching improves dramatically with these shampoos.

2) Am I allergic or irritated by minoxidil?


If there is a concern about allergy, I advise patients to apply the minoxidil twice daily to the inner forearm for 1-2 weeks and observe if an irritation or true allergy develops. This is called a “repeat open application test” (ROAT). Photos should be take daily and shown to a physician. A dermatologist can guide if a true allergic contact dermatitis has developed. Some patients are allergic or highly irritated by the ingredients in the formulation (such as propylene glycol in the liquid form) but some a truly allergic to minoxidil. A dermatologist can perform a standard patch test if doubt still exists after the patient performs and analyzes the ROAT.

It irritation to propylene glycol is suspected, minoxidil can be made up (compounded) in 20 % glycerin, 20 % water and 60 % ethanol. The fact that the patient in this question is still itchy with the PG free “foam” formulation makes it less likely the glycerin compounded formulation is actually going to help. As an alternative 2 % minoxidil can be used as it often has less PG.

3) Do I actually have another itching diagnosis that has been missed?


In situations like this, one always needs to keep an open mind that another itching diagnosis is present too or instead. This is not a common scenario but one can imagine a patient with lichen planopilaris (LPP) who was misdiagnosed as having AGA. Minoxidil can make active LPP worse.

In summary, there are many reasons to be itchy from minoxidil. Only in more severe cases does it cause hair loss. A methodical approach often reveals the cause and best options to reduce itching. Readers may also be interested in my previous article

I’m Itchy from Minoxidil: What Should I do?

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Finasteride Use and Breast Cancer in Women

Question:

I read your recent article discussing the risk of breast cancer in spironolactone users. Do women using finasteride place themselves at increased risk of breast cancer?

ANSWER:

Thanks for the question. We received quite a few inquiries last week when I posted this question:

Does Using Spironolactone Increase the Risk of Breast Cancer?

This week, I’d like to address the evidence for another group of antiandrogens known as the 5 alpha reductase inhibitors. This includes finasteride and dutasteride. To date, there is no good evidence to support the notion that use of oral anti-androgens such as finasteride or spironolactone are associated with an increased risk of breast cancer in women either in the general population or in women at increased risk of breast cancer. For finasteride, studies in women have never been done and we rely entirely on studies in males at low risk. For women, only a few studies have looked at breast cancer risks in spironolactone users. These studies have not suggested an increased risk of cancer in spironolactone users who are at low risk for breast cancer. 

 We do not have data on the risk of breast cancer in users of anti-androgens at highest risk. If the patient or her treating physicians feels that her risk of breast cancer may be higher than current estimates then the drug might not be used given that we have no information about the risks in these high risk groups.  I will first address what is known at present about the risk of breast cancer from finasteride and then address how a patient may come to get a better estimate of risk.  References for all the studies discussed are provided at the end.

 

Finasteride and Breast Cancer Risk: No studies in Women

For finasteride-related risk, the best means we have in the present day of addressing this question is by looking at the risk of breast cancer in men using finasteride and extrapolating the data the best we can to estimate the potential risk in female users.  We do not have studies in women. Male breast cancer is a rare condition with a lifetime risk of 0.1 %. In men, its behavior is similar to breast carcinoma in postmenopausal women.  So while studying male breast cancer and extrapolating the information to female breast cancer is not ideal, it is the best method we have in the present day.

There have been case reports and clinical trial results that suggested that treatment with 5ARIs may be associated with male breast cancer. Most studies to date however, suggest that it is not. All data needs to be taken into context with all available data to date. It should be noted that a warning label has been placed on finasteride packaging in many countries until this issue is further evaluated. An evidence review by the United Kingdom’s (UK) national drug agency resulted in a finasteride drug warning label for breast cancer in the UK and Canada and initiation of an FDA safety probe for all 5ARIs in 2010.

 

It is impossible to ascertain risk of cancer from the original short duration clinical trials. In other words, one is not going to get a sense of the risk of breast cancer by looking up a journal article about a 1 or 2 year study with finasteride. It’s far too short of a period. This is because such typical clinical trials are neither large enough nor have long enough follow-up to identify male breast cancer cases in men who use finasteride. The best type of studies we have at present are observational studies where men with breast cancer are compared to men without breast cancer. Such “case-control studies” are an invaluable tool to assess this important question. I will review many such case control studies below. 

 

A. 2016-2018 PUBLISHED STUDIES ON FINASTERIDE AND BREAST CANCER IN MEN

 

Meijer and colleagues recently assessed the possible relationship between finasteride and breast cancer by combining nationwide registers in 4 countries (Denmark, Finland, Norway, and Sweden) to assess the potential association between finasteride and male breast cancer.  A cohort of all males with dispensed finasteride (1,365,088 person years) was followed up for up to 15 years for breast cancer, and compared to a cohort of males not receiving finasteride.  An increased risk of male breast cancer was found among finasteride users (IRR = 1.44, 95% confidence interval [95% CI] = 1.11-1.88) compared to nonusers.  The analyses suggested possible ascertainment bias and did not support a clear relationship between dispensed finasteride and male breast cancer.  

Hagberg et al conducted a cohort study with nested case–control analyses using the UK Clinical Practice Research Datalink. 5ARI users did not have an increased risk of breast cancer compared to unexposed men (OR=1.52, 95% CI 0.61–3.80).

 

B. 2013-2015 PUBLISHED STUDIESON FINASTERIDE AND BREAST CANCER IN MEN

In 2014, Duijnhoven and colleagues in the Netherlands performed acase-control study with data from the United Kingdom Clinical Practice Research Datalink database among all men aged 45 years and older. Cases of men diagnosed with breast cancer were matched to up 10 controls. There were 398 cases were identified and matched to 3,930 controls. The “ever use” of 5-ARIs was associated with an adjusted odds ratio for breast cancer of 1.08 (95 % CI 0.62-1.87) compared to non-users. Increasing cumulative duration of treatment showed no increasing risks. The conclusion here in Duijnhoven’s study was that there was no evidence of an association between short- or long-term treatment with 5-ARIs and the risk for breast cancer in older men.

In 2013, Bird and colleagues in the United States published a cased control study of men age 40 to 85 years old. Here there were 339 breast cancer cases matched to 6,780 controls. There were no statistically significant associations observed between 5α-reductase inhibitors and breast cancer regardless of exposure assessment. Their conclusion was that the lack of an association in our study suggests that the development of breast cancer should not influence the prescribing of 5α-reductase inhibitor therapy.

 

C. 2003-2012 PUBLISHED STUDIESON FINASTERIDE AND BREAST CANCER IN MEN

In the 2003 PCPT study, Thompson and colleagues published data on 18882 men aged 55 years or older who were randomized to treatment with 5 mg/day finasteride (n = 9423) or placebo (n = 9459) for 7 years. One case of breast cancer was reported as an adverse experience in each treatment group during the study.  In this very large long-term study, an increased incidence of breast cancer in the finasteride group compared to placebo was not observed.

The main study that drew attention to a potential relationship between finasteride and breast cancer was a 2003 study by McConnell. In this study, 3047 patients were randomized to a double-blind, multi-center, placebo-controlled clinical trial for 4-6 years. The 4 different patient groups were administered different drugs: placebo; 8 mg doxazosin; 5 mg finasteride and a combination of 8 mg doxazosin and 5 mg finasteride. Three cases of breast cancer occurred in the finasteride-treated group and 1 case of breast cancer occurred in the combination group. No predisposing factors were identified. Duration of treatment ranged from 1.8 years to 5 years. The occurrence of 4 cases of breast cancer in 3047 patients was considered high considering the normal incidence in the general population of 1 case in 100,000 man-years. Treatment with finasteride appeared in this study to confer 200-fold risk for breast cancer in comparison to patients not receiving the drug.

 

D. 1996-2002 PUBLISHED STUDIES ON FINASTERIDE AND BREAST CANCER IN MEN

 

In 1996, Prescription Event Monitoring (PEM) Study was published. This study was conducted by Drug Safety Research Unit (DSRU) and involved a total of 14,772 patients (mostly male) under observation of General Practitioners from 1992–1994. There were 2 reported breast carcinomas. For one of the events, the time to onset from commencement of finasteride treatment was recorded as 5 months, the other was unknown. The PEM study in 1996 concluded overall that that finasteride is acceptably safe when used in accordance with the current prescribing information.However, it is not possible from this study to evaluate the cases of breast cancer and their causal relationship with finasteride, as enough data is not available regarding the 2 events of breast carcinoma.

 

In 1998, McConnell and colleagues published the Proscar long term efficacy and safety study (PLESS). There were 3040 patients were followed up for a period of 4 years. The patients were randomized in approximately equal proportions to receive either 5 mg finasteride or placebo for up to 4 years. In this study, there were no cases of male breast cancer reported in finasteride-treated subjects, and 2 cases were reported in placebo-treated subjects.

Summary and Conclusion

The evidence to date does not point to an association between finasteride or dutasteride use and breast cancer in women at low risk. It is absolutely critical to keep in mind that the studies I have mentioned above above were conducted in men with low risk of breast cancer and not in women (and not in women who have high baseline risks of breast cancer and not in women who already have breast cancer). Also most of the studies have looked at finasteride rather than dutasteride but of course some of the studies looked collectively at both types of alpha reductase inhibitors. This is important to keep in mind. Many physicians continue to avoid avoid prescribing any type of anti androgen to patients with a history of breast cancer (or at highest risk of breast cancer) given that no such studies have been done. However, for most women, there is no evidence to suggest that their use of finasteride or dutasteride increases their risk of developing breast cancer.

REFERENCES

 

1.    Hagberg KW, et al. Risk of gynecomastia and breast cancer associated with the use of 5-alpha reductase inhibitors for benign prostatic hyperplasia. Clin Epidemiol. 2017.

2.     Wiebe JP, et al. Progesterone-induced stimulation of mammary tumorigenesis is due to the progesterone metabolite, 5α-dihydroprogesterone (5αP) and can be suppressed by the 5α-reductase inhibitor, finasteride. J Steroid Biochem Mol Biol. 2015.

3.     Meijer M, et al.  Finasteride treatment and male breast cancer: a register-based cohort study in four Nordic countries. Cancer Med. 2018.

4.     Duijnhoven RG, et al. Long-term use of 5α-reductase inhibitors and the risk of male breast cancer. Cancer Causes Control. 2014.

5.    Bird ST, et al. Male breast cancer and 5α-reductase inhibitors finasteride and dutasteride.

J Urol. 2013.

6.    McConnell JD, Bruskewitz R, Walsh P, Andriole G, Lieber M, Holtgrewe HL, et al. The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia. N Engl J Med. 1998;338:557–63.  

 

7.    McConnell JD, Roehrborn CG, Bautista OM, Andriole GL, Jr, Dixon CM, Kusek JW, et al. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Eng J Med. 2003;349:2387–98 

8.    Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG, et al. The Influence of finasteride on the development of prostate cancer. N Engl J Med. 2003;349:215–24.

9.    Wilton L, Pearce G, Edet E, Freemantle S, Stephens sMD, Mann RD. The safety of finasteride used in benign prostatic hypertrophy: a non-interventional observational cohort study in 14,772 patients. Br J Urol. 1996;78:379–84.  

10.  Mackenzie IS, et al. Spironolactone use and risk of incident cancers: a retrospective, matched cohort study. Br J Clin Pharmacol. 2017.

11. Biggar RJ, et al. Spironolactone use and the risk of breast and gynecologic cancers. Cancer Epidemiol. 2013.

12.  Mackenzie IS, et al. Spironolactone and risk of incident breast cancer in women older than 55 years: retrospective, matched cohort study. BMJ. 2012.

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Does using spironolactone increase the risk of breast cancer?

Question

I have been prescribed spironolactone for female pattern hair loss but have heard confusing information about whether or not the drug increases the risk of breast cancer. Do women using spironolactone have an increased risk of breast cancer?

Answer

Thanks for the great question. I’ll answer this with some depth but I’ll begin by saying that the most recent well conducted studies do not support an association between breast cancer and the use of spironolactone in women at low risk for the disease.

Concerns about the possibility of an increased risk of cancer from spironolactone date back to 1975. Studies at the time showed that rats ingesting spironolactone (at 25–250 times the exposure dose in humans) for 2 years developed several types of tumors including benign adenomas of the thyroid and testes, malignant mammary tumors, and growths on the liver.

To date, there is no good evidence to support the notion that women using spironolactone are at increased risk for breast cancer. In the most recent 2017 study, McKenzie studied the risk of cancer among users of Spironolactone. The participants were 74 272 patients exposed to spironolactone between 1986 and 2013 using the Clinical Practice Research Datalink from the UK. In this study, there was no increased risk of cancer in spironolactone users. 

In 2013, Biggar published data specifically looking at the risk of breast cancer in female spironolactone users. The researchers used anationwide prescription drug registry between 1995 and 2010 and identified use of spironolactone in a cohort of Danish women (≥20 years old).  After studying 2.3 million women (28.5 million person-years), the authors concluded that with respect to breast, uterus, ovarian and cervical cancer, there is no evidence of increased risk with spironolactone or furosemide use.

In 2012, McKenzie published a study a retrospective cohort study evaluating whether exposure to spironolactone treatment affects the risk of incident breast cancer in women over 55 years of age. The study involved 1,290,625 female patients, older than 55 years and with no history of breast cancer, from 557 general practices with a total follow-up time of 8.4 million patient years.  Although the vast majority of women were using doses under 100 mg, 17.2 % of women in the study were using 100 mg doses and 3.6 % were using 200 mg doses. The data suggested that the use of spironolactone did not increase the risk of breast cancer.

 

Summary and Conclusion

The evidence to date does not point to an association between spironolactone and breast cancer in women at low risk. These studies above were conducted in women with low risk of breast cancer and not in women at highest risk and not in women who already have breast cancer. This is important to keep in mind. Many physicians continue to avoid avoid prescribing spironolactone to patients with a history of breast cancer (or at highest risk of breast cancer) given that no such studies have been done. However, for most women, there is no evidence to suggest that their use of spironolactone increases their risk of developing breast cancer.

References

Barker DJP. The epidemiological evidence relating to spironolactone and malignant disease in man. J Drug Dev. 1978;1(Suppl 1. 2):22–25.

Biggar RJ, et al. Spironolactone use and the risk of breast and gynecologic cancers.Cancer

Epidemiol. 2013.

Danielson DAN, Jick H, Hunter JR, et al. Nonestrogenic drugs and breast cancer. Am J Epidemiol. 1982;116:329–332. 

Mackenzie IS, et al. Spironolactone use and risk of incident cancers: a retrospective, matched

cohort study. Br J Clin Pharmacol. 2017.

Mackenzie IS, et al. Spironolactone and risk of incident breast cancer in women older than 55

years: retrospective, matched cohort study. BMJ. 2012.

 

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