Tuesday, 17 October 2017

PCOS and Hair Loss, Part 2: Medical Treatments

Image by Kelly Martin, Wikimedia Commons

For several years this blog has had an ongoing series about different aspects of PCOS (Polycystic Ovarian Syndrome) and its treatments. Today we continue talking about a tough subject: PCOS and hair loss (alopecia).

In our past PCOS series, we have discussed the definition and symptoms of PCOS, how it presents, its testing and diagnosis, and its possible causes. We've also discussed the increased risk for endometrial cancer among those with PCOS.

Now we are discussing common treatment protocols for PCOS, and the pros and cons of each. We've already discussed insulin-sensitizing medications like metformin, the TZDs, and inositol. Then we discussed glucose-lowering medications for those who have developed overt diabetes.

We have also discussed anti-androgenic medications and progesterone supplements for menstrual irregularity. In addition, we did a 3-part series on birth control pills for PCOS.

Now we are talking about one of the least-discussed symptoms of PCOS, Alopecia Androgenetica (AGA, also called female-pattern hair loss or FPHL).

In Part One, we discussed what alopecia is, how it's diagnosed, and what might cause it. Today in Part Two, we'll discuss some of the medical treatments available for it. Finally, in Part Three, we'll discuss some of the cosmetic treatments that women with hair loss utilize, based on suggestions found on hair loss forums and PCOS boards.

If you have personal experience or expertise in any of these areas, please share in the comments section. You are welcome to do so anonymously if you prefer. Please be respectful.
Disclaimer: I am not a medical health-care professional. This information is not medical advice about a health condition or treatment. Consult your healthcare provider before making any decisions about your care plan.
What causes thinning hair in PCOS?

No one knows exactly what causes Androgenetic Alopecia in women with PCOS. Likely there is a genetic predisposition from family members, combined with excess androgen levels or an increased sensitivity to even modest levels of androgens. Dihydro-Testosterone (DHT) seems to be the androgen most commonly linked to alopecia.

The Wikipedia entry on Alopecia describes the process this way:
In genetically prone scalps (i.e., those experiencing male or female pattern baldness), DHT initiates a process of follicular miniaturization, in which the hair follicle begins to deteriorate. As a consequence, the hair’s growth phase (anagen) is shortened, and young, unpigmented vellus hair is prevented from growing and maturing into the deeply rooted and pigmented terminal hair that makes up 90 percent of the hair on the head. In time, hair becomes thinner, and its overall volume is reduced so that it resembles fragile vellus hair or "peach fuzz" until, finally, the follicle goes dormant and ceases producing hair completely.
The Cochrane Database describes androgenetic alopecia in the following way:
It is characterised by progressive shortening of the duration of the growth phase of the hair with successive hair cycles, and progressive follicular miniaturisation with conversion of terminal to vellus hair follicles (terminal hairs are thicker and longer, while vellus hairs are soft, fine, and short). 
Not every woman with AGA has high levels of androgens. As one website points out:
The role of androgens in female pattern hair loss is not fully established. Scalp hair loss is undoubtedly a feature of hyperandrogenism in women but many women with female pattern hair loss do not have higher levels of circulating androgens. However, they have been found to have higher levels of 5α-reductase (an enzyme that catalyzes the irreversible reduction of testosterone to dihydrotestosterone), more androgen receptors, and lower levels of cytochrome P450 (which converts testosterone to estrogen).
So you don't have to have high levels of testosterone in order to experience Androgenetic Alopecia:
Testosterone converts to DHT with the aid of the enzyme Type II 5-alpha reductase, which is held in a hair follicle's oil glands. Scientists now believe that it's not the amount of circulating testosterone that's the problem but the level of DHT binding to receptors in scalp follicles. DHT shrinks hair follicles, making it impossible for healthy hair to survive. 
The bottom line is that no one truly understands why hair loss happens in PCOS, nor why only some women are affected and not others. However, most traditional medical treatments are based around a few key concepts, including hypothyroidism, nutritional deficiencies, insulin resistance, inhibition of androgens, and increasing blood flow to the scalp.

Hypothyroidism

Doctors usually start with ruling out co-morbidities. Since many women with PCOS have subclinical hypothyroidism (often auto-immune in nature), poor thyroid function may be one potential cause of alopecia in PCOS.

Controversy surrounds what lab readings should indicate a diagnosis of hypothyroidism. Many endocrinologists balk at treating people with "borderline" TSH readings, because many people with borderline readings are not symptomatic and do not seem to benefit from treatment. However, those who are borderline but symptomatic often report significant improvements through treatment.

If you have symptoms of hypothyroidism, be sure to educate yourself thoroughly on these controversies and remember that there is significant disagreement among medical professionals as to when and how to deal with it. Treatments may differ quite strongly from one provider to another. Don't be afraid to get a second opinion. You may need to see a care provider who is more open to "alternative" treatments in order to get borderline readings taken seriously.

Anecdotally, women with borderline hypothyroidism often find that their hair loss slows down considerably when they get their thyroid levels optimized. Treatment usually involves taking thyroid replacement hormones. Traditional treatment involves T4 treatment, but some find medications utilizing both T3 and T4 to work best for them. Read more here and here for debates about thyroid medications and testing.

Nutritional Deficiencies

Nutritional deficiencies may also play a role in hair loss in some cases, especially in women with hypothyroidism.

Low Ferritin Levels

Research suggests that iron-deficiency anemia is associated with hair loss. Even when hemoglobin and hematocrit levels are normal, it is still possible to have low ferritin levels (a measure of stored iron). It is important to have multiple types of iron levels tested.

Many people with hypothyroidism have higher rates of iron-deficiency anemia (low ferritin levels). Why is not clear. People with hypothyroidism tend to have low stomach acid, which decreases their absorption of iron. Some people report improvement by increasing stomach acid or taking special digestive enzymes (Betain, Pepsin) or probiotics to help increase their absorption of iron. Others report improvement when they eliminate gluten from their diets or optimize their hypothyroid medications.

A hypothyroidism-low ferritin connection is also likely because many women with hypothyroidism have very heavy periods, especially as they approach perimenopause, and this can cause low ferritin. Many of these women need regular supplementation with iron until after they go into menopause. A recent pregnancy (or series of pregnancies) or incidents involving significant blood loss can also result in low iron stores.

It's important to have other possible causes investigated too. For example, a low ferritin level could indicate chronic intestinal bleeding from colo-rectal cancer.  A colonoscopy should be considered for chronically low ferritin levels, especially in older adults or those with symptoms like blood in the stool.

Iron supplements can cause constipation; herbal supplements like Floradix may be easier on the system. Take iron supplements with Vitamin C or acidic foods like orange juice or apple cider vinegar to increase its absorption. Avoid calcium foods, tea, coffee, and antacids within a few hours of your iron supplement. If you take a thyroid medication in the morning, take your iron supplement in the evening.

However, don't supplement with iron unless you have documented that you have low iron levels. Too much iron in the blood can be toxic. If you do end up taking iron supplements, keep them strictly out of the reach of children because iron ingestion is one of the most common sources of poisoning in children.

Some advocates say that if ferritin levels can be raised and maintained above about 70, some hair regrowth can occur. Anecdotally, this seems to work well for some women but not for others. But since low ferritin levels and hypothyroidism affect your health in so many other ways too, it's important to treat these conditions whether or not it results in regrowth of hair.

Low Vitamin D Levels

Women with PCOS often have chronically low levels of Vitamin D too, which may also be associated with Female Pattern Hair Loss as well as Alopecia Areata. Symptoms of low Vitamin D levels can include frequent illness, fatigue, muscle aches, depression, and impaired wound healing.

Low Vitamin D levels are associated with decreased insulin sensitivity, increased Body Mass Index (BMI), hyperparathyroidism, and with markers for Metabolic Syndrome. Supplementation with Vitamin D may improve insulin levels, parathyroid levels, and possibly blood sugar in some women with PCOS, but evidence is somewhat contradictory.

It's important to have your Vitamin D levels tested to be sure treatment is even needed, to be sure your calcium levels are not already high (as they often are with hyperparathyroidism), and to have some idea of how aggressive you need to be with supplementation.

Unfortunately, people with higher BMIs and people of color are often not very responsive to Vitamin D supplementation. It may take higher-than-normal doses and long-term supplementation to raise Vitamin D levels for those groups, or for those with a chronic deficiency. Some evidence suggests that a combination of Calcium plus Vitamin D supplementation might have the best effects.

meta-analysis of Vitamin D and PCOS studies suggests dosages of 1000 IU (International Units) to suppress parathyroid levels, and 4000 IU to improve Vitamin D levels in high BMI people. Other sources suggest no more than 2000 IUs without frequent monitoring but points out that treatment recommendations depend on initial lab results. Mega-dosing should be avoided as it easy for vitamin levels to get out of balance.

It is unclear whether Vitamin D supplementation would help with hair loss but since it helps in so many other ways and since low D levels are also associated with hypertension and cardiac disease, women with PCOS should have their Vitamin D levels tested periodically, get reasonable levels of sunshine, and consider supplementation when needed.

Other Nutrient Deficiencies

Sometimes women with hypothyroidism have other significant nutrient deficiencies. For example, there have been case reports of women whose hair loss improved only after treatment for both hypothyroidism and zinc deficiencies. If in doubt, have your nutrient levels tested.

A good, well-rounded diet with plenty of colorful fruits and vegetables ("eat the rainbow") is always a good idea for minimizing the possibility of nutrient deficiencies. However, it is possible to develop deficiencies even with good nutrition. Some people just don't absorb nutrients as well as others. An impaired gut biome may be one reason for this, so some people believe in using probiotics. Food sensitivities to things like gluten may also impair nutrient absorption; anecdotally some people find great improvement by eliminating gluten or other foods. Experiment and see what works for you.

It should also be noted that many women with PCOS are encouraged to consider radical weight loss procedures like gastric bypass or other procedures. However, these surgeries can cause severe nutritional deficiencies over time, and these nutritional deficiencies can also play a role in hair loss after weight loss surgery. Possible deficits of iron, ferritin, zinc, D, and B12 should be investigated. Taking your vitamins religiously is a vital part of your care after weight loss surgery.

Insulin Resistance Treatment

Some research has found that women with strong insulin resistance have higher levels of alopecia. Because PCOS is so often associated with hyperinsulinism, reducing insulin levels is a cornerstone of PCOS treatment. Research is very clear that insulin-sensitizing medications and behaviors improve PCOS outcomes. It is less clear is whether they have any effect on AGA hair loss.

Lifestyle

Most experts recommend that the first course of treatment for PCOS always be lifestyle modification. For many doctors this means intentional weight loss, but given the poor long-term success rates of weight loss, the potential risks of weight cycling, and the substantial risk for yo-yoing up the scale, many women chose to focus on lifestyle while de-emphasizing the scale. They use lab work and how they respond to nutrition and exercise to measure success rather than a measuring tape or BMI.

Increasing exercise is one of the most important methods of lowering insulin resistance. Frequency and regularity of exercise is more important than intensity. Find the type of exercise you enjoy most and make it a regular part of your life.

As noted, a healthy diet high in fruits and vegetables is always a good idea. Moderating carb intake and emphasizing complex carbs over simple carbs is sensible and doesn't have to be extreme. Taking several small meals throughout the day instead of larger, more carb-intensive meals is helpful. Be sure to always have some protein with your carbs to avoid insulin spikes and blood sugar instability.

Some women with PCOS find their best results by following a paleo or extremely low-carb lifestyle. Others prefer to eliminate so-called "inflammatory" foods such as gluten, grains, and dairy. Also popular these days is so-called "slow foods" eating, using mostly natural, non-processed, home-cooked organic foods.

However, be careful of Food Fascism. Dietary rigidity can easily turn into an eating disorder, and too many restrictions often result in over-consumption or even binge eating. Be suspicious of the latest diet trend; look for an approach that can be done in a common-sense, reasonable way that can be sustained over time. More realistic results may be had through moderation of certain carbs or foods rather than complete banishing of them. Moderation tends to be the key to long-term, sustainable lifestyles, but each person must find the nutritional approach that works best for her.

Many women also try to eliminate additional toxins in their environment from things like plastics, antibiotics and hormones in meats, chemicals in their yards, etc. Getting enough sleep and ensuring you don't have sleep apnea (or are adequately treated for it) can also help blood sugar and insulin levels.

All of these things are simply common sense but bear mentioning as a first step in treating the underlying causes and symptoms of PCOS. In that way, they might theoretically help AGA hair loss, but in real life, most PCOS women do not report long-term hair regrowth through nutrition or lifestyle. Still, reasonably done, they are unlikely to hurt and might help some.

Insulin-Sensitizing Medications

Although lifestyle can help, most women with PCOS find they need help to lower their insulin levels further. There are a number of medications available which can help lower insulin levels and improve blood sugar. We have covered these extensively on this blog before so we won't go into them in detail here. The most common choices include:
Although there is extensive research on the effect of these medications on the metabolic and hirsutism symptoms of PCOS, there is very little research on their effect on hair loss. Still, because they are so effective at reducing other problems associated with PCOS, they should be considered a basic part of PCOS care, whether or not they help hair loss.

Anti-Androgen Treatments for Alopecia

Many women with PCOS have elevated levels of testosterone, and this can translate to increased levels of DHT. As noted, even those without elevated testosterone levels may have a predisposition to increased conversion of existing testosterone to DHT. In genetically predisposed women, this may lead to hair thinning. Therefore, anti-androgens are seen as a cornerstone of traditional medical treatment for hair loss.

Most women's hair loss websites promote a double-pronged approach to Androgenetic Alopecia. First, they suggest using anti-androgen medications to slow down or stop the hair loss, and then they suggest using a hair regrowth product like minoxidil.

Most sites note that it can take quite a while to tell whether or not a medication is helping alopecia. 12-24 months is a considered a minimum trial period for anti-androgens. If you try these medications, be sure to give them a long enough try before you make any conclusions about their usefulness to you.

Anti-Androgen Medications

We've already discussed anti-androgen medications in a previous post on this blog, but let's review them again here briefly. The primary anti-androgens used for alopecia include:
  • spironolactone
  • cyproterone acetate
  • finasteride
  • dustasteride
Anti-androgen medications work in several ways:
Anti-androgens can be used to block the effects of androgen in the pilosebaceous unit or in the hair follicle. Anti-androgen therapy works through competitive antagonism of the androgen receptor (spironolactone, cyproterone acetate, flutamide) or inhibition of 5α-reductase (finasteride) to prevent the conversion of T to its more potent form, 5α-dihydrotestosterone.
It's important to note that any hair loss benefits last only as long as the anti-androgen is taken. That means the patient must remain on the medication for life or face reversal of the benefits.

Spironolactone (Aldactone)

Spironolactone combined with an oral contraceptive is one of the most common treatments for Female Pattern Hair Loss.

Spironolactone is a synthetic steroid which acts as an androgen receptor antagonist, and can be used to combat hirsutism (excess body hair) in women with PCOS. Because it is a postassium-sparing diuretic, it has the bonus effect of treating hypertension (high blood pressure), which is also common in women with PCOS.

Spironolactone may help stop or slow down hair loss in women. It is not as successful at restoring hair that has stopped growing, but some women find that it can slow down the loss.

There is some limited research to suggest that it can result in at least some hair slowing or regrowth in about 40% of women with PCOS. Other research reports positive results in about 75% of women with FPHL. One study discusses its use in women with FPHL:
Spironolactone has been used for 30 years as a potassium-sparing diuretic. Spironolactone is a synthetic steroid structurally related to aldosterone. Since the serendipitous discovery 20 years ago that spironolactone given to a woman for polycystic ovary syndrome (PCOS) and associated hypertension also improved hirsutism, it has been used as a primary medical treatment for hirsutism. Spironolactone both reduces adrenal androgen production and exerts competitive blockade on androgen receptors in target tissues. Spironolactone has been used off-label in FPHL for over 20 years. It has been shown to arrest hair loss progression with a long-term safety profile. A significant percentage of women also achieve partial hair regrowth.
Side effects can include vomiting, diarrhea, dizziness upon changing position, menstrual spotting, breast tenderness, and electrolyte imbalances. Potassium levels, electrolytes, and kidney function must be monitored while on this drug. Because spironolactone can cause birth defects, it must be used with a highly effective form of birth control or in women who absolutely cannot conceive.

Cyproterone acetate (Androcur, Cyprostat)

Cyproterone acetate (sometimes abbreviated as CPA) is an anti-androgen drug available outside the United States. According to Wikipedia:
Cyproterone acetate is a synthetic steroidal anti-androgen drug. It has additional progestogen and anti-gonadotropic properties. Its primary action is to suppress the activity of the androgen hormones such as testosterone and its more potent metabolite dihydrotestosterone (DHT) in the body, effects which it mediates via competitive antagonism of the androgen receptor and inhibition of enzymes in the androgen biosynthesis pathway. The main therapeutic indications of cyproterone acetate are prostate cancer, benign prostatic hyperplasia, priapism, hypersexuality (e.g., as a form of chemical castration), and other conditions in which androgen action maintains the disease process. In addition, it can also be used to treat acne and hirsutism in females, and is a common component in hormone therapy for transsexual women. 
In addition to its antiandrogen properties, cyproterone acetate has weak progestogen activity (i.e., it acts like progesterone). Accordingly, it can be used to treat hot flashes, and is also a component of some combined oral contraceptive pills such as Dianette in the United Kingdom and Diane-35 in other countries such as Canada. It is called Dixi-35 in Chile. No form of cyproterone acetate is available in the United States.
CPA is a powerful anti-androgen. Side effects can include depression, B12 deficiency, sexual dysfunction, liver damage, weight gain, breast tenderness, blood clotting issues, fatigue, and irritability. In women, it is often prescribed with a birth control pill, and this combination has been shown to be a significant risk factor for blood clots.

Although it is prescribed in other countries for treatment of AGA hair loss, its efficacy for that purpose is unclear. Although it has some effect on hair growth, it does not seem to work any better than spironolactone. Its risk for birth defects and blood clots may make it an undesirable trade-off for hair loss treatment.

Flutamide

Flutamide is another anti-androgen medication. It is usually used to reduce androgens in men with prostate cancer. It is also fairly effective in treating hirsutism in PCOS. According to one review article:
Flutamide is an oral anti-androgen that acts by competitively inhibiting the uptake of androgen and its nuclear binding in target tissues.
According to this same review, there is some limited research indicating it can be useful against hair loss in women in a dose of 250 mg. It was effective even in women who were resistant to other anti-androgen medications.

However, flutamide carries a significant risk for liver toxicity, and liver function must be carefully monitored if this medication is used. It can also result in significant gastrointestinal upset. Presumably, it also carries the same risk for birth defects as other anti-androgens and should be used only with extremely effective contraception or in post-menopausal women.

Finasteride 

Finasteride (Propecia) is a type II 5-alpha reductase inhibitor. It inhibits the enzyme that converts testosterone into dihydrotestosterone (DHT), thereby slowing down its effects on hair follicles and perhaps even reversing hair loss.

It is an oral pill, taken once per day. Side effects can include headaches, nausea, sexual dysfunction, depression, and hot flashes. It can also cause birth defects if pregnancy inadvertently occurs. Its use for male pattern hair loss is approved by the FDA, but its use in women is not approved in the U.S.A. However, it is not unusual for it to be prescribed off-label for women too.

Finasteride works modestly well on hair loss in men. A research review of finasteride use in women shows that there is some data to support its efficacy. However, most of this evidence is based on uncontrolled trials and anecdotal case reports; controlled trials do not seem to show the same effect. A 2016 Cochrane Review found that finasteride worked no better than placebo in the studies reviewed. However, a 2017 research review found that while low doses (1 mg) of finasteride provided no benefit, higher doses (2.5 mg or 5 mg daily) did provide some hair regrowth. More research is needed.

Even without strong quality evidence of efficacy, many care providers are willing to prescribe this medication on the off-chance that it will help; prolonged use may be necessary (at least 1 year, possibly more) before knowing whether or not it works for any one person.

Because of its strong potential for birth defects, finasteride is used only in women without childbearing potential. Some care providers will prescribe it for women of childbearing age in conjunction with highly effective contraceptive methods like the Pill. However, even highly effective methods like the Pill can fail under real-world conditions, so many doctors will not prescribe finasteride to women before natural or surgical menopause.

Dutasteride

Dutasteride is another 5-alpha-reductase inhibitor, but it is reportedly more potent than finasteride. Most research has been done on men, although some positive results have been reported in women's hair loss. It is not approved for FPHL in the U.S.A.

Side effects in women may include headache, G.I. issues, dizziness, change in sexual function, and acne. Like finasteride, it may also lead to an increase in estrogen levels and thus possibly increase the risk for breast cancer. Again, because of the very strong potential for birth defects, most doctors will not prescribe it to women with child-bearing potential.

Other Medications for Alopecia

There are other medications besides anti-androgens that can be considered for alopecia. These include oral contraceptives, minoxidil, prostaglandin analogues, and ketoconazole.

Combination Oral Contraceptives

Certain combination oral contraceptives (using both estrogen and progestin) have strong anti-androgen effects. As a result, they are often the first-line treatment for PCOS and for hirsutism in general. They can also be somewhat effective for androgenic hair loss in some women

However, the strength of anti-androgenic effect in oral contraceptives varies. Some birth control pills (second generation, especially those involving levonorgestrel) have strong androgenic effects, which can make symptoms worse in women with PCOS.

Many of the later oral contraceptives (third- and fourth-generation) have a stronger anti-androgenic effect. These can be used on their own or in combination with other anti-androgenic drugs (usually spironolactone) to treat hirsutism, alopecia, and acne.

Unfortunately, the oral contraceptives with the strongest anti-androgenic effects tend to have the strongest risk of blood clots, particularly for women of size and/or women with PCOS. Each woman's unique medical history and risk factors must be considered very carefully before use of these oral contraceptives. You can read more about these risks herehere, and here.

Rogaine (Minoxidil)

Minoxidil is a hair growth stimulator. It was originally a blood pressure medication. It worked by dilating small blood vessels in the body, but was found to have the side effect of hair growth, probably by enhancing cell proliferation. One dermatology website notes:
A Cochrane systematic review published in 2012 concluded that minoxidil solution was effective for FPHL. 
Minoxidil works modestly for some people, but many people don't find it that effective. If it does work to regrow your hair, most often the hair that grows is very fine. That can help reduce the shininess of seeing scalp underneath hair, but is not a return to your normal hair.

Minoxidil comes in different strengths, 2% and 5%. Both are now available over the counter. Side effects are more common with the stronger version and can include:
  • Fast or irregular heartbeat; 
  • Weight gain (rapid) of more than 5 pounds (2 pounds in children)
  • Chest pain; shortness of breath
  • Bloating; flushing or redness of skin; swelling of feet or lower legs
  • Numbness or tingling of hands, feet, or face
  • Skin rash and itching
  • Hair growth in undesired areas
Some users report that minoxidil is heavy in texture (almost greasy) and tends to make hair "clump" together. As a result, it may make the thinning look worse. Because of this, many people stop using it after a while. They reason there's little good in using a product to help regrow the hair if it makes your thinning hair look worse at first. On the other hand, some are able to combine minoxidil with a cosmetic product to help cover up any problems until regrowth appears.
Those who have used minoxidil report that it can take a long time to show effect. They are often told that they must try it for at least 6 months to know if there is any effect. Some dermatologists also prescribe a topical retinoid alongside minoxidil in order to increase efficacy.

Prostaglandin Analogues 

Prostaglandins are lipid-derivative compounds in your body that have a hormone-like effect, and which may show some usefulness in treating hair loss. Like minoxidil and anti-androgens, though, the benefit would only last as long as you take the medication.

PGD2 prostaglandins bind to the GPR44 receptor on the skin and this blocks hair growth, causing balding. The prostaglandin analogue medications would turn off this action, stopping the hair loss process. However, while prostaglandin D2 analogues may have a role to play in stopping AGA hair loss, it may take a combination of two different drugs to regrow lost hair:
Prostaglandins have been demonstrated to have the ability in modulating hair follicle cycle; in particular, PGD2 inhibits hair growth while PGE2/F2a promote growth. Due to the progressive nature of AGA, the treatment should be started early and continued indefinitely, since the benefit will not be maintained upon ceasing therapy.
Some have speculated that decreasing omega-6 fatty acid foods and increasing omega-3 foods in the diet will have the same effect, but this is unproven.

Latanoprost and Bimatoprost are two possible prostaglandin analogues of the PGE2/F2 variety. Bimatoprost (trade name Latisse) was originally a glaucoma drug for reducing pressure in the eyes, but was found to increase eyelash hairs. It is now marketed to the general public in the U.S. for increasing eyelash growth and can be helpful in people with alopecia areata. At least one study found its application on the scalp resulted in increased hair density, but the study was extremely small, short, and limited in scope.

Setipiprant is another prostaglandin drug in the pipeline. It is a PGD2 inhibitor primarily used for adults with asthma and allergies. It is currently undergoing clinical trials for various uses.

There was a lot of buzz about prostaglandin analogues around 2012; may people thought they were going to be THE new hair loss treatment. However, this buzz has dropped off considerably; if these drugs really worked as well as hoped, the buzz would undoubtedly still be there. Still, that doesn't mean that there is no future for them. Rather, there is a strong need for more research into them, their efficacy for hair loss, and their possible side effects. You can read more about prostaglandin analogues here, here, and here.

Ketoconazole

Ketoconazole is an ingredient used in an anti-dandruff shampoo, usually called Nizoral. It is a strong anti-fungal, which is why it can help some cases of dandruff. It also helps reduce itching, and since many people who are losing their hair experience increased scalp itching, they may appreciate its anti-itch effects.

Ketoconazole, used in a stronger prescription strength, has also been reported as a treatment for baldness. Used topically (as a cream) or orally, it is thought to curb the production of testosterone and have anti-inflammatory action. It is also considered an androgen receptor antagonist, competing with DHT at the androgen receptor sites in the scalp. In this way, it is thought to help hair loss.

Some limited research supports the idea that it may help to slow down hair loss. However, some critics suggest that perhaps its anti-fungal properties merely clear away sebum and unclog the hair follicles, as it were, improving their blood supply and making it easier for them to function again.

Some hair loss forums recommend using Nizoral shampoo (available in the 1% version over the counter, or in the 2% version by prescription) every few days to calm down the scalp and allow it to heal so that other products (like minoxidil) can work better. Whether this is truly helpful or not is anyone's guess.

Although oral ketoconazole has been available for many years, the FDA has recently issued a warning about its potential for liver toxicity and adrenal damage. Except for very rare indications, it recommends against oral prescriptions of ketoconazole. However, the shampoo does not seem to be included in these warnings.

You can read more about ketoconazole here or here.

Alternative Treatments for AGA

Of course, these medications are not the only option for treating Female Pattern Hair Loss. There are several other procedures that are used in hair loss. Many women with PCOS also use various herbs, foods, vitamins, and essential oils.

However, there is not a lot of research to show which of these treatments are effective and which are not, whether any have drug interactions with other substances, or what the side effects of these supplements might be. Therefore, be cautious in using these approaches, especially in combining them with each other or with other medications.

Other Hair Loss Treatments

There are other treatments for hair loss available. Some of the most common include hair transplants, Platelet-Rich Plasma Therapy (PRP), Low-Level Laser Light Therapy (LLLT), and Tricomin Therapy Spray.


Hair Transplants

One option many people know about is hair transplantation. Basically, the doctor takes hair plugs from around the bottom part of your scalp (slightly above the neck area, the area least likely to thin) and moves them to the thinnest areas. If they take well, then you have increased naturally growing hair in the thin areas.

The problem is that this does not stop the thinning process around them from continuing and as a result, these hair plugs will only stand out more strongly with time. Furthermore the process is quite costly and invasive.

The consensus seems to be that hair transplants can offer more fullness for a while, but are a poor long-term choice for managing androgenetic hair loss in women.  
Platelet-Rich Plasma Therapy (PRP)

Platelet-Rich Plasma therapy takes blood from the patient, uses centrifuges to separate out the platelets and various growth factors, adds back some plasma, and then sprays on or injects the mixture directly into the thinning areas of the scalp. This helps with tissue regeneration and increasing blood flow and is starting to be used to promote wound healing in several medical fields outside of hair loss.

One research paper describes PRP this way:
Platelet-rich plasma (PRP) is autologous concentration of platelets contained in small volume of plasma which accelerates the rejuvenation of skin and hair follicles (HFs) due to presence of various growth factors and cellular adhesion molecules.
Some research (and some anecdotal stories) seem to suggest some hair regrowth is possible with this treatment, increasing the density and thickness of hair in treated areas, but not all research has found it effective. Furthermore, existing research has been criticized for being too small to be meaningful, lacking controls, and for using highly inconsistent standards for treatment protocols and measuring efficacy. More research is needed on the benefits and risks of this approach for women with PCOS hair loss. 

Low-Level Laser Light Therapy (LLLT)

Another possible treatment includes Low-Level Laser Light therapy (LLLT). In this, a hat, hood, comb, or other device is equipped with red-light lasers that have just enough power to penetrate the scalp. There are a couple of devices that have FDA approval in the U.S. They project low-level infrared radiation into the scalp. Treatments are done 2-3x per week over an extended period of time.

LLLT tends to work best on people whose pattern balding is not yet very advanced. It works by stimulating blood flow in the scalp in order to shift more follicles into anagen phase (growing phase instead of resting or shedding phase) and prolonging that growth phase. It does seem to promote some degree of hair growth, but the question is how long this hair growth lasts since sooner or later those follicles are going to go into a shedding or resting phase. You can read more about how LLLT works here and here.

LLLT is somewhat controversial among dermatologists. Some believe it has little use in treating hair loss, while others see some benefit. Some studies have shown modest benefits, including in women with AGA, but the quality of the research is questionable; most trials have a high risk of bias, are too short to be meaningful, or have other methodological problems. At best, LLLT may produce some short-term hair re-growth but it seems unlikely to have long-lasting results. Better-quality research is needed.

Tricomin Therapy Spray

Tricomin sprays use copper peptides to stimulate new hair growth. It is supposed to shorten the "resting" (telogen) phase of the follicles so more follicles are in the active phase at once. Copper also inhibits the production of DHT.

Tricomin spray is topically applied to the scalp. It is sometimes used in conjunction with minoxidil or oral finasteride in men. Evidence for its utility is mostly anecdotal. You can read more about Tricomin Therapy Spray and other products here.

Various Nutritional and Herbal Supplements

Despite uncertainty over efficacy and side effects, many women with PCOS are willing to experiment with herbs, supplements, and essential oils in hopes of lessening their hair loss. You can read a more complete list of these here or here, but beware the possible conflicts of interest in these sites, as many sell or have links to companies promoting these products. Caveat Emptor!

Commonly recommended supplements for lessening hair loss in PCOS include Saw Palmetto extract, NAC, MSM, methyl vanillate, biotin, and many miscellaneous herbs and other supplements.

Saw Palmetto Extract 

Saw Palmetto (Serenoa Repens) is a common herb that acts as a testosterone suppressant, so there is less testosterone to turn into DHT. It may act similarly to Propecia in that it blocks the enzyme 5-alpha reductase that helps the body turn testosterone into DHT. It may also block receptor sites on cell membranes which allow the absorption of DHT. It has been called "Nature's Propecia."

Most commonly used in older men as a treatment for an enlarged prostate, its use has expanded into the hair loss field because of its blocking actions on 5-alpha reductase. It is typically taken in doses of 200-320 mg daily for at least six weeks. Side effects can include gastrointestinal disturbances, nausea, dizziness, headaches, faintness, and liver problems. It may increase blood pressure and cardiovascular issues, and may have some blood-thinning effects so it should not be taken in conjunction with other blood thinners.

Saw Palmetto is available over the counter or from herbalists. It should be taken with food in order to lessen G.I. issues. The berries of the plant are dried and turned into an extract, used in tablets or capsules. Only the tablets and capsules have been investigated; teas made from the dried berries are unlikely to be useful because the active components reportedly aren't water soluble.

There is not a lot of research on the efficacy of Saw Palmetto Extract. Some research suggests it is mildly effective, but not nearly as effective as finasteride.

Saw Palmetto must not be taken during pregnancy or while trying to conceive; like the anti-androgen drugs, it may cause serious birth defects. It should not be used while nursing because of a lack of information about its bioavailability in breastmilk. It should not be taken with hormonal birth control, as it may reduce the birth control's efficacy. 

N-acetyl Cysteine (NAC) 

N-acetyl Cysteine (NAC) is often recommended in alternative approaches to PCOS. NAC is thought to reduce testosterone and insulin resistance.

NAC for PCOS has mostly been investigated for its effect on fertility, hormonal imbalances, menstrual regularity, and insulin sensitivity. It has shown mostly good effects in these areas. It has compared favorably with metformin in some studies. That's impressive for a so-called "alternative" supplement.

Anecdotally, women with PCOS report that NAC is particularly useful for hirsutism (unwanted facial and body hair). However, while some PCOS sites also recommend NAC for scalp hair loss, there doesn't seem to be a lot of actual research investigating whether it is effective for this purpose. It is just presumed to be effective because of its effect on testosterone levels. Actual research into its use for PCOS-related AGA is needed.

MSM

Methylsulfonylmethane, commonly abbreviated as MSM, is a sulfur-based chemical often used for pain or swelling in the joints (arthritis). People using it for this purpose reported improvement in their nails and hair, and so it became popular for treatment of hair loss. An experiment on mice also seemed to show some improvement in hair regrowth.

MSM is thought to be important for hair growth by producing the protein keratin and by strengthening hair follicles. It comes in tablets, capsules, creams, and powders. There is very little evidence of its utility in treating hair loss in humans. 

Methyl Vanillate

Methyl Vanillate is a plant-derived medication that is delivered topically via a spray. Some small studies have found it to be helpful but the small size of the studies and lack of controls mean the results are not very powerful.

Biotin

Biotin is a B vitamin (B7) that is routinely recommended by many hair loss resources because it is thought to help with hair growth. However, there is little research that supports its routine use in most hair loss patients.

Case reports have found that in those with brittle nails or severe symptoms of a biotin deficiency, biotin supplements may indeed be useful in treating hair loss.

However, several research reviews have found that it is more of a trendy treatment than one supported by clear evidence of efficacy in most people with hair loss. Most experts agree it would not be useful unless there is clear evidence of a biotin deficiency.

Various Other Supplements

There are many other alternative supplements often recommended to women with PCOS and AGA. These commonly include:
  • Green Tea Extract - Contains an anti-oxidant which also helps block the enzyme 5-alpha reductase
  • Spearmint Tea - Spearmint herb tea has reportedly been shown to lower testosterone levels and balance hormones when taken regularly (about 16 oz. daily) 
  • AvocadoFood which reportedly blocks testosterone from turning into DHT
  • Tea Tree Oil - Essential oil that inhibits fungal infection and stimulates the scalp
  • Various B Vitamins - Thought to help with hair growth, especially B12 if low
On many PCOS support forums, women combine many MANY supplements to treat their various symptoms. Of course they have the right to pick and choose their own treatment protocols. Personally, though, I'm quite leery of combining therapies without knowing more about how they interact. The more supplements you take, the more potential for bad interactions. Even completely natural supplements or vitamins can be harmful in too high a dosage or in combination with certain medications. So if you plan to use supplements, try to add only one at a time, and watch carefully for potential side effects.

Summary of AGA Treatment Options

Alopecia Androgenetica is a relatively uncommon symptom of PCOS. Far more women with PCOS experience hirsutism instead, and most women with PCOS will never develop hair loss.

However, up to 1/3 of women with PCOS will develop some degree of alopecia, some to very significant levels, and it can be one of the most devastating symptoms of PCOS. 

Women with PCOS hair loss often say they learn to deal with other PCOS symptoms, but AGA remains particularly challenging. In a world that measures a woman by her "feminine" appearance, losing the hair on the head can be incredibly traumatic.

If you have PCOS and hair loss, start by investigating possible causes of hair loss like hypothyroidism or nutritional deficiencies, since these can be common in PCOS. Remember, your hair loss may be caused by a combination of factors rather than only one. Investigate them all. Consult a dermatologist so your hair loss can be properly evaluated.

Once other problems have been ruled out, most dermatologists will recommend a hair regrowth topical treatment combined with an anti-androgen, as long as strong steps are taken to prevent childbearing potential. Most often, the combination proposed is spironolactone and minoxidil:
Hormonal treatment, i.e. oral medications that block the effects of androgens (e.g. spironolactone, cyproterone, finasteride and flutamide) is also often tried. 
A combination of low dose oral minoxidil (0.25 mg daily) and spironolactone (25 mg daily) has been shown to significantly improve hair growth, reduce shedding and improve hair density. 
Once started, treatment needs to continue for at least six months before the benefits can be assessed, and it is important not to stop treatment without discussing it with your doctor first. Long term treatment is usually necessary to sustain the benefits.
These treatments work modestly well as long as you keep doing them. Unfortunately, they are not good choices for women of childbearing age who are sexually active. They are particularly not useful to women with PCOS who are planning to have children, are pregnant, or are breastfeeding.

Of the commonly recommended hair loss medications, only minoxidil and finasteride are officially approved  in the U.S.A. for use in AGA hair loss (and finasteride is not approved for women). However, a recent review suggests that "these medications offer mediocre results, lack of a permanent cure, and potential complications."

Of course, there are any number of alternative treatments touted for hair loss, based around the same goals of decreasing androgens, fixing nutritional deficiencies, decreasing insulin resistance, and increasing blood flow to the scalp. Some people swear by these treatments, but there is limited research on their efficacy and safety. Remember that there is a high degree of quackery and profiteering in this field and take any recommendations for them with a BIG grain of salt.

Most women with FPHL who decide to fight their hair loss use a combination of treatments. They might address insulin resistance via exercise, moderation of carb intake, and medications; androgen excess through spironolactone, finasteride, or supplements; hair regrowth through topical medications like minoxidil; possible nutrient deficits through nutritional supplements if labs indicate the need; and scalp blood flow through PRP or LLLT. They might address all of these areas, a few of them, or only one or two. Every woman is different in what risks and side effects she is willing to tolerate.

The future holds several possible treatments for Female Pattern Hair Loss, but far more research needs to be done before they become standard of care. One panel of experts evaluated investigational and future treatments for AGA and concluded:
We propose that topically applied medications, or intra-dermal injected or implanted materials, are preferable treatment modalities, minimizing side effect risks as compared to systemically applied treatments. 
Evidence in support of new treatments is limited. However, we suggest therapeutics which reverse the androgen-driven inhibition of hair follicle signaling pathways, such as prostaglandin analogs and antagonists, platelet-rich plasma (PRP), promotion of skin angiogenesis and perfusion, introduction of progenitor cells for hair regeneration, and more effective ways of transplanting hair, are the likely near future direction of androgenetic alopecia treatment development.
Whatever treatment you choose, be realistic. Don't expect a cure. Keep in mind that none of these hair loss treatments are very effective. At best, some may slow down hair loss or generate modest temporary regrowth, but they are unlikely to stop or fully reverse hair loss, and none restore a full head of hair.

As a result, many women with hair loss turn to cosmetic solutions, which can be effective in disguising or covering up hair loss. More on that in the next post in the series.


References

General Information on Alopecia
PCOS and Prevalence of Alopecia Androgenetica

J Family Reprod Health. 2016 Dec;10(4):184-190.Clinical and Biochemical Characteristics in PCOS Women With Menstrual Abnormalities. Christodoulopoulou V, Trakakis E, Pergialiotis V, Peppa M, Chrelias C, Kassanos D, Papantoniou N. PMID: 28546817
...MATERIALS AND METHODS: We conducted a prospective observational study of patients 17-35 years of age with PCOS that attended the department of Gynecological Endocrinology of our hospital. RESULTS: A total of 309 women with PCOS participated in the study. In total, 72.2% suffered from menstrual cycle disorders...36% of the sample had androgenetic alopecia and 56.4% had acne....
Eur J Endocrinol. 2003 Nov;149(5):439-42. Prevalence of polycystic ovaries in women with androgenic alopecia. Cela E, Robertson C, Rush K, Kousta E, White DM, Wilson H, Lyons G, Kingsley P, McCarthy MI, Franks S. PMID: 14585091. Free full text can be found here.
...We...set out to determine the strength of the association between androgenic alopecia and PCO...SUBJECTS AND METHODS: We studied 89 women of mixed ethnic origin with androgenic alopecia and compared them to 73 control women...RESULTS: Women with alopecia had a higher prevalence of PCO and hirsutism than the control population (PCO: 67% vs 27%, P<0.00001; hirsutism: 21% vs 4%, P=0.003). Women with alopecia (with or without PCO) had higher testosterone, androstenedione and free androgen index than controls, even though few had frankly abnormal androgens. CONCLUSIONS: These findings confirm an association between androgenic alopecia and PCO, and other symptoms of hyperandrogenaemia. Thus most women who present with androgenic alopecia as their primary complaint also have PCO and have indices of abnormal androgen production....
FPHL: General Treatment Overviews

Cochrane Database Syst Rev. 2016 May 26;(5):CD007628. doi: 10.1002/14651858.CD007628.pub4.
Interventions for female pattern hair loss. van Zuuren EJ, Fedorowicz Z, Schoones J. PMID: 27225981
...MAIN RESULTS: We included 47 trials, with 5290 participants, of which 25 trials were new to this update. Only five trials were at 'low risk of bias', 26 were at 'unclear risk', and 16 were at 'high risk of bias'.The included trials evaluated a wide range of interventions, and 17 studies evaluated minoxidil...AUTHORS' CONCLUSIONS: Although there was a predominance of included studies at unclear to high risk of bias, there was evidence to support the efficacy and safety of topical minoxidil in the treatment of FPHL (mainly moderate to low quality evidence). Furthermore, there was no difference in effect between the minoxidil 2% and 5% with the quality of evidence rated moderate to low for most outcomes. Finasteride was no more effective than placebo (low quality evidence). There were inconsistent results in the studies that evaluated laser devices (moderate to low quality evidence), but there was an improvement in total hair count measured from baseline.Further randomised controlled trials of other widely-used treatments, such as spironolactone, finasteride (different dosages), dutasteride, cyproterone acetate, and laser-based therapy are needed. 
Dermatol Clin. 2013 Jan;31(1):119-27. doi: 10.1016/j.det.2012.08.005. Epub 2012 Oct 11. Hair: what is new in diagnosis and management? Female pattern hair loss update: diagnosis and treatment. Atanaskova Mesinkovska N, Bergfeld WF. PMID: 23159181
Female pattern hair loss (FPHL) is the most common cause of alopecia in women. FPHL is characterized histologically with increased numbers of miniaturized, velluslike hair follicles. The goal of treatment of FPHL is to arrest hair loss progression and stimulate hair regrowth. The treatments for FPHL can be divided into androgen-dependent and androgen-independent. There is an important adjuvant role for nutritional supplements, light therapy, and hair transplants. All treatments work best when initiated early. Combinations of treatments tend to be more efficacious.
Int J Womens Health. 2013 Aug 29;5:541-556. Female pattern alopecia: current perspectives. Levy LL, Emer JJ. PMID: 24039457
Hair loss is a commonly encountered problem in clinical practice, with...women exhibiting diffuse hair thinning over the crown (increased part width) and sparing of the frontal hairline (Ludwig classification). Female pattern hair loss has a strikingly overwhelming psychological effect; thus, successful treatments are necessary. Difficulty lies in successful treatment interventions, as only two medications - minoxidil and finasteride - are approved for the treatment of androgenetic alopecia, and these medications offer mediocre results, lack of a permanent cure, and potential complications. Hair transplantation is the only current successful permanent option, and it requires surgical procedures. Several other medical options, such as antiandrogens (eg, spironolactone, oral contraceptives, cyproterone, flutamide, dutasteride), prostaglandin analogs (eg, bimatoprost, latanoprost), and ketoconazole are reported to be beneficial. Laser and light therapies have also become popular despite the lack of a profound benefit. Management of expectations is crucial, and the aim of therapy, given the current therapeutic options, is to slow or stop disease progression with contentment despite patient expectations of permanent hair regrowth. This article reviews current perspectives on therapeutic options for female pattern hair loss.
Anti-Androgen Medications for Androgenetic Alopecia

Brough, KR and Torgerson, RR. Hormonal Therapy in Female Pattern Hair Loss. International Journal of Women's Dermatology. 2017 Mar;3(1):53-57. Free full text here.

Dermatol Clin. 2010 Jul;28(3):611-8. Innovative use of spironolactone as an antiandrogen in the treatment of female pattern hair loss. Rathnayake D, Sinclair R.  PMID: 20510769
...Although androgens play a key role in the pathogenesis of male pattern hair loss (MPHL), the role of androgens in female pattern hair loss (FPHL) is less well established. Satisfactory treatment response to antiandrogen therapy supports the involvement of androgens in the pathogenesis of FPHL. Spironolactone has been used for 30 years as a potassium-sparing diuretic. Spironolactone is a synthetic steroid structurally related to aldosterone. Since the serendipitous discovery 20 years ago that spironolactone given to a woman for polycystic ovary syndrome (PCOS) and associated hypertension also improved hirsutism, it has been used as a primary medical treatment for hirsutism. Spironolactone both reduces adrenal androgen production and exerts competitive blockade on androgen receptors in target tissues. Spironolactone has been used off-label in FPHL for over 20 years. It has been shown to arrest hair loss progression with a long-term safety profile. A significant percentage of women also achieve partial hair regrowth. Spironolactone is not used in male androgenetic alopecia because of the risk of feminization.
Br J Dermatol. 2005 Mar;152(3):466-73. Treatment of female pattern hair loss with oral antiandrogens. Sinclair R, Wewerinke M, Jolley D.   PMID: 15787815 
...METHODS: For this single-centre, before-after, open intervention study, 80 women aged between 12 and 79 years, with FPHL and biopsy-confirmed hair follicle miniaturization [terminal/vellus (T/V) hair ratio < or = 4 : 1] were photographed at baseline and again after receiving a minimum of 12 months of oral antiandrogen therapy. Forty women received spironolactone 200 mg daily and 40 women received cyproterone acetate, either 50 mg daily or 100 mg for 10 days per month if premenopausal. Women using topical minoxidil were excluded...RESULTS: As there was no significant difference in the results or the trend between spironolactone and cyproterone acetate the results were combined. Thirty-five (44%) women had hair regrowth, 35 (44%) had no clear change in hair density before and after treatment, and 10 (12%) experienced continuing hair loss during the treatment period... CONCLUSION: Eighty-eight percent of women receiving oral antiandrogens could expect to see no progression of their FPHL or improvement....
Dermatol Online J. 2008 Mar 15;14(3):1. A review of hormonal therapy for female pattern (androgenic) alopecia. Scheinfeld N. PMID: 18627703
...Approximately 10 percent of pre-menopausal women show evidence of androgenetic alopecia. Age increases the incidence and 50-75 percent of women 65 years or older suffer from this condition. Only 2 percent topical mindoxidil is approved for treating female androgenetic alopecia. Reviews suggest that anti-hormonal therapy (e.g. cyproterone acetate, spironolactone) is helpful in treating female pattern alopecia in some women who have normal hormone levels. The use of hormonal therapies is most extensively studied in post-menopausal women. Several studies have suggested that cyproterone acetate with or without ethinyl estradiol and spironolactone can ameliorate female androgenetic alopecia in women with normal hormone levels, but larger controlled studies need to be done. Flutamide was found to be more effective than spironolactone or cyproterone in one study. Testosterone conversion inhibitors have been tried in post-menopausual women with normal hormone levels to treat alopecia. No study has shown that 1 mg of finasteride effectively treats female androgenetic alopecia but doses of 2.5 and 5 mg finasteride have helped some women in a few open studies. One case report notes the utility of dutasteride after finasteride failed. The role and place of anti-androgentic agents in female androgenetic alopecia in both pre and post-menopausal women remains to be fully defined. The need for effective agents is highlighted by the paucity of effective treatments and the substantial psychosocial impact of alopecia on women.
Ann Pharmacother. 2010 Jun;44(6):1090-7. doi: 10.1345/aph.1M591. Epub 2010 May 4. Finasteride treatment of hair loss in women. Stout SM, Stumpf JL. PMID: 20442354
OBJECTIVE: To review available evidence on the safety and efficacy of finasteride in the treatment of alopecia in women...Treatment successes with finasteride in women with female pattern hair loss, although an off-label indication, have been primarily described in uncontrolled studies and anecdotal reports. In 2 controlled clinical studies, finasteride showed no benefit over placebo or no treatment in female pattern hair loss. A finasteride regimen of 1 mg orally daily, as indicated in male pattern hair loss, may be recommended for those who fail or cannot tolerate minoxidil therapy. A 12-month trial is needed to assess stabilization of hair loss, and hair regrowth may take 2 years or longer. Although data are sparse, menopausal status, circulating androgen concentrations, and concomitant symptoms of hyperandrogenism do not appear to predict response to finasteride. Overall, finasteride is well tolerated; however, women of childbearing potential must adhere to reliable contraception while receiving finasteride, and treatment is contraindicated in pregnancy, due to known teratogenicity. CONCLUSIONS: Although objective evidence of efficacy is limited, finasteride may be considered for treatment of female pattern hair loss in patients who fail topical minoxidil treatment.
Australas J Dermatol. 2007 Feb;48(1):43-5. Treatment of female pattern hair loss with a combination of spironolactone and minoxidil. Hoedemaker C et al. PMID: 17222303
A 53-year-old woman with clinical evidence of female pattern hair loss and histological evidence of androgenetic alopecia was initially treated with the oral antiandrogen spironolactone 200 mg daily. Serial scalp photography documented hair regrowth at 12 months; however, the hair regrowth plateaued, and at 24 months there had been no further improvement in hair density. Twice daily therapy with topical minoxidil 5% solution was then introduced and further regrowth documented, confirming the additive effect of combination therapy.



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