Male and female pattern hair loss

[Music] Welcome to the Australian Prescriber podcast. An independent, no-nonsense podcast for busy health professionals.

I'm Dhineli Perera, your host for this episode, and it's a pleasure to be chatting to Dr Laxmi Iyengar and Dr Jane Li today about the perennial problem of male and female pattern hair loss. Dr Laxmi is a dermatology research fellow at the Skin Health Institute, GP and adjunct lecturer at Monash University. Dr Jane Li is a consultant dermatologist at the Skin Health Institute, St. Vincent's Hospital in Melbourne as well as Eastern Health. Together they'll help to demystify this age-old topic. Welcome to the program, Laxmi and Jane.

LI: Thank you.

JL: Thank you. It's a pleasure to be here.

Dr. Laxmi, perhaps you can start us off and tell us what AGA [androgenetic alopecia] is and why is it a difficult condition to manage?

LI: So AGA is otherwise known as androgenetic alopecia and it's also commonly known as patterned hair loss or male and female pattern hair loss. And it is thought to be genetically mediated and driven by the action of androgens. And the hormone that's usually implicated is known as dihydrotestosterone, which is a product of testosterone metabolism and it's an extremely common condition. So about 80% of males by the age of 80 suffer from hair loss and female pattern hair loss can actually affect some younger women as well. About 12% of women before the age of 30 and 40% of women by the age of 50.

And it is a difficult condition to manage, as you mentioned, because it is generally only partially reversible and treatments are designed either to promote new hair growth or arrest further hair loss. And it's also confusing for patients because there are an array of treatments in the market, they're quite expensive and they all have varying levels of evidence. It is quite confusing and patients really need to be appropriately counselled by clinicians from the outset, especially about expectations and also about the rationale of how the various treatments work as well.

So there's a lot that needs to be really clarified for patients.

LI: Absolutely.

What is the difference between the 2 forms of alopecia you mentioned in the article?

LI: Yeah, that's a really important question. So alopecias are broadly categorised into 2 categories. There's the scarring and the non-scarring alopecias, and this is really an essential skill for a clinician to be able to distinguish between. Now, the key finding in a scarring alopecia is loss of the follicular openings and that is best determined by using a dermatoscope on the scalp, which is also known as trichoscopy. Sometimes with the scarring alopecias you can see some scaling and folliculitis as well as loss of the follicular openings. And scarring alopecias warrant urgent referral to a dermatologist so patients can access more specialised treatment, and this is because scarring alopecias can result in permanent hair loss and the scalp is replaced with scar tissue. Thankfully, androgenetic alopecia is actually a form of non-scarring alopecia, so that means that the follicular openings are still preserved, so it is at least partially reversible.

Laxmi, could you tell us a little bit more then about AGA and how it manifests in men and women? Does it manifest the same way?

LI: No, it actually manifests differently. Both males and females with androgenetic alopecia will report generalised hair thinning, but female patients may report progressive hair shedding and they may also comment loss of their ponytail volume. The other finding in females tends to be the widening of the middle partition of the crown, and this is often known as a Christmas tree pattern by clinicians. A male, in contrast, may state that they have bitemporal hairline recession and also they commonly report loss of hair over the scalp vertex as well as the generalised hair thinning. So the presentation of androgenetic alopecia is actually quite distinct between men and women.

Right. It's important to know those 2 distinctions when trying to diagnose that. Jane, reading your paper, it sounds like trichoscopy, which Laxmi's just mentioned, is that particularly important diagnostic tool. Could you tell us a bit more about it, what it is and how do prescribers access it?

JL: Yeah, well, before we talk about trichoscopy, we might briefly explain dermoscopy, which is essentially the use of a handheld device known as a dermatoscope, to examine the skin with magnification and also light. So trichoscopy is using the same tool, a dermatoscope, to examine the hair and the scalp. There's really small differences, for example, on the scalp we tend not to use a liquid interface, but otherwise it's quite similar. It's a very accessible type of test. You just need a dermatoscope and a scalp to examine. So a dermatoscope has magnification of about 10 times, it's non-invasive, and with practice, you can identify specific patterns and signs to point you towards or against various differential diagnoses. So for example, in androgenetic alopecia, the main finding on trichoscopy is miniaturisation of the hairs. You can see hair shafts with varying diameters in the thinning areas and, as Laxmi already mentioned, importantly the hair follicles, the follicular ostia, the openings are preserved. So if they're lost, especially if they're lost in great numbers, that would point to a scarring hair loss condition, not androgenetic alopecia.

So what is the hair pull test then?

JL: The hair pull test is a bedside test that's done by the clinician. It's used to check the activity and severity of hair shedding. This generally involves holding about 50 to 60 hairs between index finger and thumb. You start near the scalp and you slowly and gently pull on those hairs by sliding your fingers down the hair shaft. So it's not a tug, it's not a yank, it's a gentle pull. So positive pull is when you get more than 2 hairs removed, per pull and we generally pull from a few defined areas. So the vertex, the parietal scalp, the occipital scalp, and in androgenetic alopecia, the hair pull test should actually be negative, but it may be positive if other conditions are also present. And importantly, I generally do not encourage patients to try the hair pull test at home on themselves.

I wouldn't trust myself to do that. I think that's good advice. My next question was to Laxmi, what are some of the differential diagnoses for AGA? What would be the top 3 identifiers for scarring alopecia?

LI: So for scarring alopecia, the important differentials to keep in mind are lichen planopilaris, which typically is associated with scaling and perifollicular redness of the scalp. So if you're using a dermatoscope, you'll be able to identify some of these features together with the loss of the follicular openings, of course. Frontal fibrosing alopecia, which is quite distinct where there's a band-like recession of the frontal scalp hairs, and also discoid lupus erythematosus, which is associated with systemic lupus, can also be associated with hair loss. For androgenetic alopecia, that's a form of non-scarring hair loss. So other more common differentials to keep in mind are things like telogen effluvium.

So this typically happens when patients present with abrupt hair loss and that's typically seen after pregnancy or a major psychological stressor, for example, where patients will come in and report that they've suddenly lost a whole chunk of their hair. Alopecia areata is also another common condition that can present, and again, it has a very distinct pattern where patients will present with well-defined bald patches on their head. And the hair pull test in alopecia areata is generally positive. In children in particular, it's important to keep tinea capitis as the differential in mind, which is a fungal infection of the scalp. There's also trichotillomania, which is hair pulling associated with psychiatric disorders, which can be associated with anxiety and depression. So it's important to bear this in mind if this applies to your patient.

Okay. Jane, could you talk us through how you might discuss treatment expectations with a patient? I’d imagine that really making sure they understand that it's not always curative is particularly important.

JL: Yes, I agree that setting expectations is super important. So I tend to frame androgenetic alopecia as a chronic condition in that it's a long-term ongoing process that we can manage, ameliorate, stabilise, improve, but not cure. So with medical therapy, eventually about 60% are satisfied with the results, especially if they start early. But for patients, even patients who have undergone a hair transplant, they are counselled to continue concurrent medical therapy as well to slow down the risk of recurrence. We generally personalise treatment plans to the patient, taking in mind their goals, their financial status, comorbidities, but most treatments require at least 6 months of active therapy before any response is seen.

And often we need combination therapy to get a response. Also, many patients worry they don't even want to start treatment because they worry that if they stop their medication someday that the hair growth they have managed to get will all be lost. And so on this point, I think there's good news and bad news. So the bad news is that yes, generally the increased hair growth that you get on therapy does tend to be lost, but the good news is it does so really slowly and gradually over 6 to 12 months and then the person sort of resets and resumes their previous natural course of hair loss, but because they have actually been on treatment for some time, they're better off than if they had done nothing at all.

So before we launch into treatments themselves, Laxmi, I wanted to ask why combination therapy is thought to be more effective than monotherapy? Have there been comparative trials?

LI: Yeah, there have been a number of comparative clinical trials actually, and I urge listeners to read our paper. There are a lot of references that'll shed light on some of these clinical trials showing that combination of treatments tend to be more effective. That's because you really need a multipronged approach to tackle hair loss because treatments are designed to either stimulate hair growth or prevent further hair loss. And really you need to do both. You need to stimulate hair growth and prevent further hair loss to maximise the response.

Okay, great to know. So it's not a one-stop shop?

LI: No.

Jane, let's start with minoxidil. So this one's an over-the-counter medication, it's topical and there are tablets that are compounded product. These products have been around for a long time and yet they aren't flying off the shelves. What's the catch? What are the adverse effects or treatment challenges that we need to advise our patients about?

JL: We might start with topical minoxidil. Sometimes patients might encounter the different ranges of topical minoxidil available as well as other hair treatments and be a bit confused and so might need some guidance in that regard. Also, it is quite pricey depending on the brand name they might go with. And responses with topical minoxidil are generally modest, variable and slow. It's something that requires dedication and commitment because you might not see a proper response for at least 12 months and asking someone to apply a topical agent twice a day every day for months and months on end is a very big ask in today's busy world.

Having said that, a topical form is generally well tolerated and the main side effects are things like allergic or irritant contact dermatitis, which can cause symptoms like stinging, itch and dandruff. The other side effect is if it works too well, people can get excessive unwanted hair growth known as hypertrichosis. As for the systemic minoxidil, if you do the topical minoxidil properly, they adhere really well. It is comparable to low-dose oral minoxidil, but the systemic forms can cause other side effects like they can lower blood pressure, cause postural hypertension, rarely fluid retention, so potential for more side effects and certainly would avoid prescribing them at all, if there's a history of cardiac disease.

Do they take as long to kick in as the topical formulation or do they work a bit faster?

JL: It's a good question. I think you're right. Generally the oral systemic formulations are thought to have a faster rate onset.

Because yeah, you're right, 12 months is a long game to try and convince anyone to do, especially without that reward happening quickly. So Laxmi, I note that spironolactone is a treatment option for women, but not men. Why is this the case and why is contraception encouraged?

LI: Spironolactone, it's actually a mineralocorticoid receptor antagonist, which means that it actually has antiandrogenic properties, which is why it's not really used for men. It does prevent hair loss effectively though in majority of patients, and it does result in hair growth that is noticeable typically after 6 months of use. Because there is a risk of feminisation of the male fetus, generally contraception is encouraged in premenopausal women, and it's generally, if possible, co-prescribed in women and it is encouraged.

Okay. That's important to know, especially again, for those younger women that might be using that treatment. And then Jane, the 5-alpha-reductase inhibitors have a different mechanism, again, different to what we've talked about so far. I guess this supports the combination therapy argument even better, right? So I note that the time to observed benefit is longer for these agents or how long are we talking?

JL: Yes, so again, 5-alpha-reductase inhibitors are similar to spironolactone in that they act on a hormonal pathway. Just to briefly explain, the 5-alpha-reductase is an enzyme that converts testosterone to dihydrotestosterone and inhibiting it. So dihydrotestosterone is the main hormone implicated in androgenic alopecia. There's 2 isoforms and in brief, finasteride inhibits the type II isoform. That's the main form that's expressed in skin and dutasteride inhibits type I and type II. The onset of action does generally fall between 6 and 12 months. It depends again on the patient. Some patients might notice an improvement earlier, but some may require the full 12 months to see any response. And certainly with [this] class of medications, there are adverse effects that we don't see with minoxidil relating to say sexual dysfunction, things like low libido, erectile dysfunction, gynaecomastia, which is growth of breast tissue in a male, and potentially mood change.

Generally these side effects if they do occur, they're quite rare, are reversible with discontinuation of the medication. But even more rarely there are reports of symptoms persisting. Also, 5-alpha-reductase inhibitors are contraindicated in women of childbearing potential for the same reason that spironolactone is contraindicated in that feminisation of the male fetus may occur. Another important point is that the 5-alpha-reductase inhibitors reduce PSA, so that's the prostate serum antigen which is used to screen for prostate cancer. So if patients are taking one of these medications for androgenetic alopecia, clinicians need to be aware so that they adjust any measured PSA concentrations that they're measuring for screening.

That's a great point. And one that probably flies under the radar I would imagine. It would require quite a good medication history to nut that out too. So Laxmi, when it comes to topical finasteride, that's the newer kid on the block. Could you tell us a little bit about that and what information is available?

LI: Phase 3 trials so far have shown some really promising results with topical finasteride. It's actually not TGA [Therapeutic Goods Administration] approved in Australia yet. And the results so far have been quite controversial because some have noted that those sexual side effects that Jane was just talking about with oral finasteride use have also been noted with topical finasteride. The reason why this is controversial is because if there is an effective oral option available, then I guess what would be the benefit of switching to topical finasteride if you are still getting those sexual side effects? In saying that it may be prescribed by some dermatologists and it may be available through compounding pharmacies if a patient sees a dermatologist who does prescribe this.

Okay, very good to know that their differences aren't huge. So Jane, when it comes to supplementation, there were quite a few mentioned in your article, what are the commonly purchased supplements and what is the evidence supporting their use?

JL: The 2 that I think have the strongest evidence base are the pumpkin seed oil and saw palmetto, usually used in combination. These compounds have been reported to exhibit antiandrogenic properties so similar in mechanism of action to say the 5-alpha-reductase inhibitors and spironolactone. But having said that, the effect is still quite modest, the evidence is certainly weaker than with prescribed medication. And so we don't generally see these commonly prescribed by clinicians.

Right. So would patients often take them themselves like maybe doing their own research online, is that where we see it used more in practice?

JL: Yeah, interestingly, I think patients actually have rarely heard of these particular 2 supplements. Often they may go for the more nutritional supplements like zinc and the combination supplements that have been labelled ‘hair and skin’. But I think those have to be taken a little bit more carefully because some formulations may contain biotin or other vitamins where high levels may affect say diagnostic testing or may actually cause side effects.

Good to know. So Laxmi, there is a huge list, a gamut of alternative treatment options mentioned in the paper. Could you describe maybe 2 for us?

LI: Sure. Like you say, there are a whole range of alternative treatment options and these all lack a strong evidence base and they've had really variable responses in clinical trials. The common ones that patients have heard about and want to know more about are, for example, the injection of platelet-rich plasma. And that's believed to have a therapeutic effect on hair loss because by injecting the platelet-rich plasma, it's thought that there is release of growth factors into the scalp which bind to receptors in the hair follicle and stimulate hair growth. If I have to pick one more that patients have talked about, I would say low-level laser therapy. These are devices that emit a low-power, monochromatic red light, and that's been shown to promote hair growth as a result of increased blood flow to the hair follicle. That's the belief. But all of these alternate treatments lack an evidence base, so you might not find many clinicians supporting these treatments.

Right. So I guess proceed with caution would be the take-home message for that.

LI: Correct, absolutely.

And so then finally, Jane, how long should GPs persist with treatment for AGA before escalation to a dermatologist?

JL: Escalating to a dermatologist should really be considered if we're not clear on the diagnosis, if patients have not responded after 6 months of active pharmacological treatment. If patients have psychological distress or if there are symptoms like pain or discomfort that don't quite fit with straightforward androgenetic alopecia. And to circle back to the trichoscopy, if we've identified loss of follicular ostia and a scarring alopecia is suspected, that is considered a hair emergency, I'll be escalating referrals sooner rather than later.

Excellent. Well thank you so much, Laxmi and Jane, but that's unfortunately all the time we've got for this episode.

JL: Thanks, Dhineli.

[Music]

Laxmi and Jane's article, Male and female pattern hair loss, is available on the Australian Prescriber website. The views of the hosts and guests on the podcast are their own and may not represent Australian Prescriber or Therapeutic Guidelines. Jane Li received an advisory payment from Bristol Myers Squibb in relation to deucravacitinib for psoriasis and received an honorarium from Cerave for delivering an educational presentation on eczema and seborrhoeic dermatitis. Laxmi has no conflicts of interest to declare. I'm Dhineli Perera and thanks for joining us on the Australian Prescriber podcast.