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?

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.

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.

Hair loss after Breast Cancer Endocrine Therapy

QUESTION



QUESTION: Many of us on breast cancer drugs like Letrazole/Zoladex end up with hair loss.  In my case, it occurred after a few months and was associated with an itchy scalp and diffuse shedding of 200+ hairs a day.  Some have become very fine.

If one stops these drugs, how long does it generally take for them to clear out of the system and stop affecting the hair?

ANSWER

Thanks for the excellent and very important question. These types of questions and their answers are important for both patients and their doctors. These issues continue to be very much overlooked in the present day and so your question has broad relevance.

I’ll review the subject broadly and then return to your question.

Endocrine Therapy for Breast Cancer.

The breast cancer drugs you are referring to are broadly classified as ‘endocrine therapy.’ These drugs include three main categories: 1) the selective estrogen receptor modulators (SERMs), 2) aromatase inhibitors (AI) and 3) GnRH agonists. These drugs have shown benefits in the adjuvant and therapeutic setting for premenopausal or postmenopausal women with early-stage or advanced breast cancer. These drugs may be taken in some cases for 5-10 years to reduce the risk of recurrence.

SERMs. The selective estrogen receptor modulators include tamoxifen, raloxifene, and toremifene. These act as competitive inhibitors of estrogen binding to estrogen receptors. From this group, tamoxifen has been the most widely used for adjuvant endocrine therapy and is still the the gold standard for premenopausal patients at risk of recurrence.

AI. By contrast,aromatase inhibitors, including letrozole, anastrozole, and exemestane. These drugs inhibit the enzyme aromatase and thereby suppress plasma estrogen levels. These drugs are now considered the preferred option for adjuvant endocrine therapy in postmenopausal patients. They all appear to be comparable in efficacy and have similar AE profiles that include hot flashes, mood disorders, osteopenia, and arthralgias.

GnRH agonists. Gonadotropin releasing hormone agonists (GnRH) are used for premenopausal women with hormone receptor–positive breast cancer Drugs like leuprolide are prescribed to suppress estrogen production by the ovary and may be combined with other endocrine therapies or chemotherapies.

Breast cancer endocrine therapy induced alopecia (BC-EIA)

Hair loss is also a potential side effect of the medications used as ‘endocrine therapy’ discussed above including the SERMs, AI, and GnRH agonist. The type of hair loss that can occur in patients using these drugs is broadly referred to as “breast cancer endocrine therapy induced alopecia (BC-EIA)”

These changes come about because of the effects of hormone changes on the hair follicle - particularly the reduction in blood levels of estrogen (or estrogen related signals that are sent into cells) that accompanies use of these drugs. The hair follicle has a highly responsive endocrine organ. It produces hormones itself and responses quickly to changes in hormones in the body.

In 2013, the a meta-analysis of 13 415 patients in 35 clinical trials revealed an overall incidence of hair loss of 4.4%. The highest incidence in this study was with with the highest incidence in tamoxifen-treated patients (25%). In 2015, Moscetti and colleagues published data showing that about 8 % of 236 women using aromatase inhibitors stopped treatment on account of their hair loss.

HAIR LOSS IN PATIENTS USING ENDOCRINE THERAPY
The short answer to your question is that there can be more than one type of hair loss associated with these types of hormone blocking drugs. The main types of hair loss that are associated with these drugs include 1) acute telogen effluvium and 2) androgenetic alopecia.



Possibility 1: The Hair Loss is From a Drug Induced Telogen Effluvium

Telogen effluvium refer to a type of hair loss whereby the affected patient notices increased daily hair shedding. Instead of finding a few hairs in the shower or sink, the individual finds dozens and dozens or even hundreds. The key point here is that the shedding rate is increased over what is normal. Telogen effluvium from a drug typically occurs 2-3 months after the drug was started and can continue in some cases if the drug is continued. if a decision is made to stop the drug, the shedding can last 6-9 months after the drug is stopped.

Telogen effluvium is not common with tamoxifen. In fact, a 2014 study by Kanti et al did not show any changes in telogen hairs in 17 women using tamoxifen who were followed for 28 weeks. Although uncommon, tamoxifen related hair cycle changes are certainly possible and tamoxifen may have a growth inhibitory effects in some situations. Clearly a pure telogen effluvium is not like to be common but it can occur. A 2010 study by Bhatia et al showed that tamoxifen loaded liposomal topical formulation actually arrested hair growth in mice.

The aromatase inhibitors can also trigger a telogen effluvium. For example, Litt’s Drug Eruption Manual lists telogen effluvium from letrozole as occurring in less than 5 % of users.

Leuprolide, the GnRH agonist sometimes used in premenopausal women with breast cancer, may also cause a telogen effluvium. Litt’s Drug Eruption Manual lists telogen effluvium from Leuprolide as occurring in less than 5 % of users.

Possibility 2: The Hair Loss is From Patterned Alopecia (Androgenetic Alopecia)

The most important concept really understand is the development of androgenetic alopecia in women using endocrine therapy for breast cancer.

It’s becoming increasingly recognized that many of the hormone blocking drugs used to treat breast cancer can cause a type of hair loss that very much resembles male and female pattern balding (also called androgenetic alopecia and also called female pattern hair loss, FPHL). This type of hair loss is associated with an actual thinning of the hair strands and generally occurs in specific areas of the scalp. Women with FPHL notice that their hair is thinner and finer and this change typically affects the central scalp and crown area. The sides and the back can be affected as well but these areas are usually less affected than then middle and top of the scalp.

The drugs used as ‘endocrine therapy’ for breast cancer can cause a type of hair loss that very much resembles FPHL. It may be that women with breast cancer with underlying susceptibilities to FPHL (based on their family history or genetics) are more likely to develop this type of hair loss when they are prescribed endocrine therapy.

This type of hair loss is important to identify because it has a different course than the telogen effluvium discussed above. FPHL that develops from endocrine therapy does not improve over time if the drug is continued. Even with stopping of the drug, the hair density may not revert back to the original density. With stopping, however, the rate of hair loss may slow down or even stop.

Let me introduce you to a few important studies.

STUDY 1: Park et al 2014

In 2014, a group in Korea reported five cases of pattern alopecia in female patients who are undergoing anticancer hormonal based therapy (with aromatase inhibitors or selective estrogen receptor modulators) for the prevention of recurrence of breast cancer after surgery. This type of patterned alopecia developed after the full recovery of global hair loss of the entire scalp due to previous cytotoxic chemotherapy. The authors proposed that the androgen-estrogen imbalance caused by the drugs was thought to be the reason for the onset of pattern alopecia in the patients.

STUDY 2: Freites-Martinez A, et al 2018

in 2018, Freitas-Martinez and colleagues performed a retrospective cohort study of 112 patients with BC-ETIA. Alopecia was attributed to aromatase inhibitors in 75 patients (67%) and tamoxifen in 37 (33%). Severity was grade 1 in 96 of 104 patients (92%), and the pattern was similar to androgenetic alopecia.

STUDY 3: Gallicchio L et al. 2013

Gallicchio’s study showed that hair thinning was common with aromatase inhibitors and the chances of developing hair loss was not dependent on the age of the patient nor whether they had received chemotherapy in the past. The study was a survey-based study including a total of 851 female patients with breast cancer receiving aromatase inhibitors. 34% reported hair loss or hair thinning during their last month of therapy, and these hair changes were independent of previous chemotherapy and age.

Possibility 3: The Hair Loss is From A Different Reason Altogether

In patients who have hair loss after breast cancer treatment, one must consider a number of possibilities and keep an open mind. A number of possible reasons for hair loss after breast cancer include:

1) hair loss in the form of a telogen effluvium from the stress associated with illness

2) hair loss in the form of a telogen effluvium from one or more surgeries and the anesthetics involved in those surgeries

3) hair loss from chemotherapy, either a temporary or permanent form

4) hair loss from another issue such as a thyroid disorder, poor diet, cancer associated weight loss, or another medication used as part of treatment.

Treatment of Breast cancer endocrine therapy induced alopecia (BC-EIA)

The ideal treatment protocol for BC-ETIA remains to be determined. Hair loss with these endocrine therapies is known to have a significant effect on quality of life and this makes it imperative to develop strategies to address the hair loss.

Stopping the drug is not always an option as doing so may put the patient and highly increased risk of breast cancer recurrence. Such discussions about stopping require a thorough review by the oncologist and dermatologist.

Minoxidil may be one option for treating BC-ETIA. Freitas-Martinez and colleagues showed in 2018 that after treatment with topical minoxidil, moderate or significant improvement in alopecia was observed in 37 of 46 patients (80%). Low level laser may also be an options but this remains to be fully evaluated. Traditional anti-androgen options for addressing androgenetic alopecia in women such finasteride and spironolactone are usually not recommended for women who have been diagnosed with breat cancer.

Summary

Your question is and excellent one and I would encourage you to speak with your doctors about these issues I have raised here. Letrozole is an aromatase inhibitor and Zoladex is a GnRH type analogue. Both of these, as reviewed above, are part of what is termed endocrine therapy. While I can’t comment on whether what you have described truly fits the definition of breast cancer endocrine therapy induced alopecia (BC-EIA), certainly your description would suggest this.

Together with your physicians you can decide whether to continue these treatments or change treatments and whether to now begin specific hair loss treatments such as minoxidil. The data to date would suggest a reasonably good chance of improvement with minoxidil. In some patients minoxidil is combined with low level laser in attempt to further stimulate growth.

We don’t yet know if women with hair loss from one type of endocrine therapy are more or less susceptible to hair loss from another type of therapy. For example, we don’t yet know if women with hair loss from an aromatase inhibitor like Letrozole are less likely to have hair loss if they switch to tamoxifen. It would seem reasonable to conclude that the effects on the hair could be different.

Even with stopping a drug that may have caused BC-EIA hair may or may not improve. Some reduced shedding may occur if a culprit drug was stopped. But the pathways that were triggered often remain triggered to some degree which means the thinning does not revert back to normal in most people. With treatment of course, there can be an improvement.

Thank you again for the question.

Reference

Bhatia A, et al. Tamoxifen-loaded liposomal topical formulation arrests hair growth in mice. Br J Dermatol. 2010

Freites-Martinez A, et al. Endocrine Therapy-Induced Alopecia in Patients With Breast Cancer. JAMA Dermatol. 2018 Jun 1;154(6):670-675. doi: 10.1001/jamadermatol.2018.045

Gallicchio L et al. Aromatase inhibitor therapy and hair loss among breast cancer survivors. Breast Cancer Res Treat. 2013;142(2):435-443.

Kanti V, et al. Analysis of quantitative changes in hair growth during treatment with chemotherapy or tamoxifen in patients with breast cancer: a cohort study. Br J Dermatol. 2014.

Moscetti L, et al. Adjuvant aromatase inhibitor therapy in early breast cancer: what factors lead patients to discontinue treatment? Tumori. 2015;101(5):469-473.

Park J, et al. Pattern Alopecia during Hormonal Anticancer Therapy in Patients with Breast Cancer. Ann Dermatol. 2014.

Sagger V et al. Alopecia with endocrine therapies in patients with cancer. Oncologist. 2013;18(10):1126-1134.

How often can I have steroid injections?

QUESTION

QUESTION: How often can scalp steroid injections be done? I have alopecia areata and receive injections into the areas of hair loss every 4-6 weeks. Can I get these injections more often? Is my current frequency considered normal or excessive?

ANSWER

Thanks for the question. Let's first review a few things about steroid injections and then circle back to your question.

Steroid injections are used to reduce inflammation and are useful in a variety of hair loss conditions including alopecia areata, lichen planopilaris, frontal fibrosing alopecia, discoid lupus, traction alopecia, central centrifugal cicatricial alopecia and Pseudopelade of Brocq as well as a few others too.

The typical dose injected ranges from 2.5 mg of steroid per mL (ie 2.5 mg triamcinolone acetonide for every 1 mL of saline used) to a maximum of 10 mg per mL. Lower concentrations reduce the chance for “atrophy” (indentations in the scalp) and so many physicians opt for lower concentrations.

Generally speaking, steroid injections are performed as close as every 4 weeks apart. There is no maximum spacing and some patients benefit from injections every 4-6 months and others come into clinic whenever their condition flares.  Injections more often than every 4 weeks are not typical.

 

20 mg every 4 weeks

A limited number of studies suggest that keeping the total dose to no more than 20 mg every 4 weeks has quite a good safety profile. This means a physician can use 8 mL of steroid solution every 4 weeks if they decide to use the 2.5 mg per mL solution. If the physician decides to use a higher concentration such as 5 mg per mL, he or she only has 4 mL available to inject. If one uses 10 mg per mL (which some physicians do), one only has 2 mL.

Some studies have suggested that injecting greater volumes of steroid solution at low concentrations works better than injecting smaller volumes of steroid solution at high concentration. For many patients, I even chose 1.5 or 2 mg per mL solutions and see how it works. Use of a 1.5 mg per mL solutions allows 15 mL of fluid to inject in the scalp (that’s 5 syringes!) ... and this goes alot further than trying to figure out where to inject 2 mL of a 10 mg per mL solution. Clearly, if low concentrations aren’t working, one needs to use higher concentrations at the next visit.

In summary, steroid injections can be performed as close as 4 weeks apart but one is not obligated to continue them at this interval. Limiting the concentration, total dose and frequency of injections helps to reduce side effects. In addition to “atrophy” discussed above, side effects can rarely include fatigue, irregular menstrual cycles in women, blood sugar changes and mood changes. These are not common. Longer term side effects to monitor include osteopenia, cataracts, weight gain and changes in blood pressure. These are quite rare with proper dosing and monitoring.

Reference

Chu TW, et al. Benefit of different concentrations of intralesional triamcinolone acetonide in alopecia areata: An intrasubject pilot study. Randomized controlled trial. J Am Acad Dermatol. 2015.

Are JAK Inhibitors Recommended for Patients with Alopecia Areata?

Question

QUESTION: I’ve heard alot about the new JAK inhibitors for alopecia areata. Do you recommend them to patients?

ANSWER

Thanks for the question. JAK inhibitors are a groups of medications that inhibit a pathway inside cells known as the janus kinase pathway. There are actually an increasing number of JAK inhibitors being studied for human disease. The best studied by far are tofacitinib (Xeljanz) and ruxolitinib (Jakafi/Jakavi). Tofacitinib is FDA approved for the treatment of rheumatoid arthritis. Ruxolitinib is FDA approved for the treatment of myelofibrosis.

There is little doubt that the JAK inhibitors are among the more consistently effective of the 26-28 medications to date that we use for alopecia areata. However, the current high cost of the drug limits their widespead use. Furthermore they are not first line for most people meaning that they are not the first treatment to consider. The first line treatment for patient with several patches of alopecia areata remains topical steroids and/or steroid injections - not a JAK inhibitor.

Nevertheless, JAK inhibitors are finding their way into the treatment algorithms for alopecia areata. Patients not responding to topical steroids or steroid injections may consider options such as diphencyprone (DPCP), anthralin, methotrexate and prednisone. However JAK inhibitors are positioning themselves as reasonable evidence-based second or third line options.

Topical JAK inhibitors are also finding a role in the  treatment of alopecia. 2 % Tofactiinib liposomal cream and 0.6 % ruxolitinib have both shown promise. These are compounded from the pill form at a compounding pharmacy. These agents are also quite expensive and require some skill and experience from the perspective of the pharmacist in how best to make up. 

In summary, I rarely recommend a JAK inhibitor as a “first line” option to a patient who has newly diagnosed alopecia areata. However for those with refractory or progressive disease, it most certainly becomes an option to consider.

You may find these previous articles of mine helpful as well:

Tofacitinib for AA: How fast does regrowth occur?

The Topical JAK Inhibitors for AA: Update on Progress

How long do we need to use tofacitininib in AA?

Topical Tofacitininib for Alopecia Areata: How much does it help?

How does the safety of tofacitinib compare to other drugs?

Why do patients stop tofacitinib?

Tofacitinib (Xeljanz) for Children and Teens

Xeljanz in Children: How young is too young?

The JAK Inhibitors for AA: More Data

A look at Inflammatory Markers in AA Treated with Tofacitinib

What blood tests do we need to monitor for patients using tofacitinib?

Ruxolitinib for AA

Topical ruxolitinib promotes eyebrow regrow

Are responses to stress altered in users of tofacitinib?

Nail alopecia areata helped by tofacitinib

Will antidepressants exacerbate my hair loss?

Question

QUESTION: Will antidepressants exacerbate my hair loss? Is is possible to get the treatment I need without making things worse, without inciting another TE?

Answer

Thanks for submitting this question. This is an important question and a common concern among many people. It's actually quite an involved question. We'll begin with the basics and then move into some important points for consideration.  The main point that individuals should be aware of is that the risk of shedding with antidepressants is a lot lower than most would think. It doesn't mean there's no risk, but it is far more likely that a person will NOT get shedding from their anti-depressant than actually experience shedding. 

Antidepressants are the third most common prescription medication in North America (behind cardiovascular drugs and anti-cholesterol drugs). Recent surveys estimate that one out of every six North Americans use some sort of psychiatric medication. About 12 % of these drugs are antidepressants.  Studies by the  National Center for Health Statistics (NCHS) have showed that the rate of antidepressant use in the United States among teens and adults increased by almost 400% between 1988–1994 and 2005–2008. Nearly 1 in 10 individuals in the United States use antidepressants. The age group with the highest use was women 40-50 where nearly 1 in 4 women between 40 and 50 taken antidepressants. Statistics in other countries around the world indicate that antidepressant use is on the rise. Antidepressant use in the UK is similar to the United States where 1 in 11 individuals used antidepressants last year. Citalopram (Celexa) and Sertraline (Zoloft) were the most commonly prescribed antidepressants in the United States. 

There are several classes of anti-depressants including selective serotonin reuptake inhibitors (SSRI's), serotonin and norepinephrine reuptake inhibitors (SNRI's), tricyclic antidepressants (TCA's), Wellbutrin and monoamine oxidase inhibitors (MAOI's).

Let's take a look at what is known about the risk of shedding (telogen effluvium) with these medications. 

Selective serotonin reuptake inhibitors (SSRIs)

Common SSRI's include fluoxetine (Prozac), citalopram (Celexa), sertraline (Zoloft), paroxetine (Paxil) and escitalopram (Lexapro). Litt's Drug eruption Manual estimates that shedding with SSRI's occurs in less than 1 in every 100 users. 

Serotonin and norepinephrine reuptake inhibitors (SNRIs)

Venlafaxine (Effexor) and duloxetine (Cymbalta) are common SNRI-based anti-depressants.  Litt's Drug eruption Manual estimates that shedding with SNRI's occurs in less than 1 in every 100 users. 

Wellbutrin

Wellbutrin is an anti-depressant that affects dopamine. Litt's Drug eruption Manual estimates that shedding with Wellbutrin occurs in less than 1 in every 100 users. 

Tricyclic antidepressants (TCAs)

Tricyclic antidepressants include a wide variety of drugs. Some preferentially inhibit the reuptake of serotonin (such as clomipramine, imipramine). Others preferentially inhibit the reuptake of norepinephrine (such desipramine and nortriptyline). Others yet are fairly balanced reuptake inhibitors of serotonin and norepinephrine (such as amitriptyline).  Litt's Drug eruption Manual estimates that shedding with TCA's occurs in less than 1 in every 100 users. 

Monoamine oxidase inhibitors (MAOIs)

MAOI's used in depression include Isocarboxazid (Marlin), Phenelzine (Nardil), Selegiline (Emsam), Tranylcypromine (Parnate). The exact incidence of telogen effluvium with these drugs is unclear, but MAOI's are generally thought to have the lowest shedding risk of all antidepressants (well under 1:100). 

Shedding with Antidepressants - Key Considerations

When a patient comes in to see me with worries that their antidepressant is causing hair loss, there are several things that need to be consider. I'll address each in turn

Possibility 1. The antidepressant is truly causing a "telogen effluvium" type hair loss

Typically, if an anti-depressant is truly implicated in a person's hair loss, the shedding starts in 4-8 weeks after starting the anti-depressant. It's a diffuse type shedding, meaning that the shedding occurs all over the scalp equally. Patients who experience shedding 6-8 months after starting the antidepressant or notice more hair loss in one area of the scalp than another probably do not have antidepressant related hair loss. Some other cause is implicated. 

Possibility 2. A telogen effluvium is present but it's not due to the antidepressant

One must always rule out other causes of excessive hair shedding in anyone who feels they are losing more hair on a daily basis.  Causes of shedding include high stress, low iron, thyroid problems, medications, dieting and internal illness. A patient who has depression from a thread problem may be shedding from the thyroid issue rather than the antidepressant they were started on.  A patient who has depression from lupus may be shedding from the autoimmune disease itself rather than the antidepressant they were started on. A careful history is essential. It is also mandatory that anyone with depression have blood tests as part of their work up for depression. All patients with depression should have already had blood tests. Similarly, it is mandatory that anyone with excessive hair shedding also have blood tests as part of their work up for excessive shedding. Many of the tests for excessive shedding are similar to the tests they may have had as part of their depression evaluation. The relevant hair related tests include hemoglobin, thyroid studies (TSH), ferritin (iron storage). Other tests may also be relevant depending on the person's specific history.  

Possibility 3. The patient has a hair condition that is different than telogen effluvium but is a close mimicker

A variety of conditions can mimic (i.e. closely resemble) "telogen effluvium" including androgenetic alopecia and diffuse alopecia areata. These need to be carefully ruled out by a dermatologist. Similarly, other scalp issues which can be worsened by depression such as seborrheic dermatitis can increase the amount of daily shedding a person experiences. 

Summary

Anti-depressants can most certainly cause hair loss. However, when a patient says to me "I think my anti-depressant is causing my hair loss" - more often than not it's actually due to another cause. Individuals with depression who have experienced previous episodes of telogen effluvium should speak with their physicians about whether the risks and benefits of both antidepressants and hair shedding. Individuals who are considering antidepressants can weigh the less than 1 % chance of developing hair shedding from the drug against the potential life altering benefits of being treated properly for depression. 

Reference

1) Litt ‘s Drug Eruption Reference Manual 14th edition 2008

2) Moore TJ, et al. Adult Utilization of Psychiatric Drugs and Differences by Sex, Age, and Race.JAMA Intern Med. 2017.

3) Laura A. Pratt et al.  Antidepressant Use in Persons Aged 12 and Over: United States, 2005–2008. NCHS Data Brief No. 76, October 2011.  https://www.cdc.gov/nchs/data/databriefs/db76.htm (accessed Jul 2 2018)