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New treatment could reverse hair loss caused by an autoimmune skin disease

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Researchers at MIT, Brigham and Women’s Hospital, and Harvard Medical School have developed a potential new treatment for alopecia areata, an autoimmune disorder that causes hair loss and affects people of all ages, including children.

For most patients with this type of hair loss, there is no effective treatment. The team developed a microneedle patch that can be painlessly applied to the scalp and releases drugs that help to rebalance the immune response at the site, halting the autoimmune attack.

In a study of mice, the researchers found that this treatment allowed hair to regrow and dramatically reduced inflammation at the treatment site, while avoiding systemic immune effects elsewhere in the body. This strategy could also be adapted to treat other autoimmune skin diseases such as vitiligo, atopic dermatitis, and psoriasis, the researchers say.

“This innovative approach marks a paradigm shift. Rather than suppressing the immune system, we’re now focusing on regulating it precisely at the site of antigen encounter to generate immune tolerance,” says Natalie Artzi, a principal research scientist in MIT’s Institute for Medical Engineering and Science, an associate professor of medicine at Harvard Medical School and Brigham and Women’s Hospital, and an associate faculty member at the Wyss Institute of Harvard University.

Artzi and Jamil R. Azzi, an associate professor of medicine at Harvard Medical School and Brigham and Women’s Hospital, are the senior authors of the new study , which appears in the journal Advanced Materials . Nour Younis, a Brigham and Women’s postdoc, and Nuria Puigmal, a Brigham and Women’s postdoc and former MIT research affiliate, are the lead authors of the paper.

The researchers are now working on launching a company to further develop the technology, led by Puigmal, who was recently awarded a Harvard Business School Blavatnik Fellowship.

Direct delivery

Alopecia areata, which affects more than 6 million Americans, occurs when the body’s own T cells attack hair follicles, leading the hair to fall out. The only treatment available to most patients — injections of immunosuppressant steroids into the scalp — is painful and patients often can’t tolerate it.

Some patients with alopecia areata and other autoimmune skin diseases can also be treated with immunosuppressant drugs that are given orally, but these drugs lead to widespread suppression of the immune system, which can have adverse side effects.

“This approach silences the entire immune system, offering relief from inflammation symptoms but leading to frequent recurrences. Moreover, it increases susceptibility to infections, cardiovascular diseases, and cancer,” Artzi says.

A few years ago, at a working group meeting in Washington, Artzi happened to be seated next to Azzi (the seating was alphabetical), an immunologist and transplant physican who was seeking new ways to deliver drugs directly to the skin to treat skin-related diseases.

Their conversation led to a new collaboration, and the two labs joined forces to work on a microneedle patch to deliver drugs to the skin. In 2021, they reported that such a patch can be used to prevent rejection following skin transplant. In the new study, they began applying this approach to autoimmune skin disorders.

“The skin is the only organ in our body that we can see and touch, and yet when it comes to drug delivery to the skin, we revert to systemic administration. We saw great potential in utilizing the microneedle patch to reprogram the immune system locally,” Azzi says.

The microneedle patches used in this study are made from hyaluronic acid crosslinked with polyethylene glycol (PEG), both of which are biocompatible and commonly used in medical applications. With this delivery method, drugs can pass through the tough outer layer of the epidermis, which can’t be penetrated by creams applied to the skin.

“This polymer formulation allows us to create highly durable needles capable of effectively penetrating the skin. Additionally, it gives us the flexibility to incorporate any desired drug,” Artzi says. For this study, the researchers loaded the patches with a combination of the cytokines IL-2 and CCL-22. Together, these immune molecules help to recruit regulatory T cells, which proliferate and help to tamp down inflammation. These cells also help the immune system learn to recognize that hair follicles are not foreign antigens, so that it will stop attacking them.

Hair regrowth

The researchers found that mice treated with this patch every other day for three weeks had many more regulatory T cells present at the site, along with a reduction in inflammation. Hair was able to regrow at those sites, and this growth was maintained for several weeks after the treatment ended. In these mice, there were no changes in the levels of regulatory T cells in the spleen or lymph nodes, suggesting that the treatment affected only the site where the patch was applied.

In another set of experiments, the researchers grafted human skin onto mice with a humanized immune system. In these mice, the microneedle treatment also induced proliferation of regulatory T cells and a reduction in inflammation.

The researchers designed the microneedle patches so that after releasing their drug payload, they can also collect samples that could be used to monitor the progress of the treatment. Hyaluronic acid causes the needles to swell about tenfold after entering the skin, which allows them to absorb interstitial fluid containing biomolecules and immune cells from the skin.

Following patch removal, researchers can analyze samples to measure levels of regulatory T cells and inflammation markers. This could prove valuable for monitoring future patients who may undergo this treatment.

The researchers now plan to further develop this approach for treating alopecia, and to expand into other autoimmune skin diseases.

The research was funded by the Ignite Fund and Shark Tank Fund awards from the Department of Medicine at Brigham and Women’s Hospital.

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MIT researchers have developed microneedle patches that are capable of restoring hair growth in alopecia areata patients, reports Ernie Mundell for HealthDay . The team’s approach includes a, “patch containing myriad microneedles that is applied to the scalp,” writes Mundell. “It releases drugs to reset the immune system so it stops attacking follicles.” 

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Cure for hair loss? Breakthrough study may pave the way for new treatment

A single molecule may hold the key to battling male- and female-pattern hair loss, recent research suggests.

In mouse experiments, scientists showed that the molecule, dubbed SCUBE3, could spark hair growth in dormant mouse follicles, and even in human ones that had been grafted onto mice. The research was described in a study published in Developmental Cell.

Hair follicles in people who are bald still have the machinery to sprout new strands, study co-author Maksim Plikus, Ph.D., professor of developmental and cell biology at the University of California, Irvine, told TODAY.

All follicles have stem cells at their base that work together to produce strands of hair, Plikus said. In people who are bald or have thinning hair , some of those stem cells don’t seem to be working, he added.

“When it comes to growing hairs, follicle stem cells need to become activated,” Plikus said. “Once activated, they divide into daughter cells that mature and come together to form a strand.”

“Most people when they lose their hair wonder if the follicles are gone,” Plikus said. “They are there, but they are dormant. The reason they are inactive is that they are not hearing signaling molecules.”

That's where SCUBE3 comes in: The molecule carries the message that tells the follicles to activate. Plikus and his colleagues showed in their experiments that when mice were given microinjections of SCUBE3, their hair grew in thick . Even human follicles that were transplanted into the mouse skin turned on when exposed to SCUBE3. The findings suggest that, in people with thinning hair, there isn’t enough SCUBE3 present.

Plikus compares a head covered with dormant follicles to a huge factory filled with 3D printers that are idling and ready to print, but are waiting for someone to push their start buttons.

It’s likely, Plikus said, that it would take very small amounts of SCUBE3 to activate dormant human hair follicles. Moreover, he suspects that treatments would need to be given only two or three times a year.

While the research on SCUBE3 is promising, getting from mouse experiments to a human treatment for baldness isn’t guaranteed, and even if SCUBE3 turns out to grow hair in people, it takes a long time to take a treatment through all of the clinical trials needed to get Food and Drug Administration approval, Plikus said.

“Right now, we are very excited about it,” Dr. Brian Abittan, director of skin and hair rejuvenation at the Mount Sinai Health System, told TODAY. “With this SCUBE3 molecule, we’re hoping to have a more precise understanding of the signaling that controls hair growth. It would be great to have another pathway to treatments.”

But, Abittan said, this is still in the preclinical stage of development.

There is still a long way to go before this could become a baldness treatment, Rui Yi, Ph.D., professor of pathology and dermatology at Northwestern University's Feinberg School of Medicine, told TODAY. “There is a big difference between a human and a mouse. Mice have short hair that grows just long enough to cover their bodies.”

Before doing a clinical trial, the researchers probably will need to do more safety testing, Yi said.

Linda Carroll is a Peabody Award-winning journalist who is a contributing health and medicine writer for NBC News and TODAY. She is co-author of three books: “The Concussion Crisis: Anatomy of a Silent Epidemic”, “Out of the Clouds: The Unlikely Horseman and the Unwanted Colt Who Conquered the Sport of Kings” and “Duel for the Crown: Affirmed, Alydar, and Racing’s Greatest Rivalry”.  

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Fda approves second yale-researched treatment for alopecia areata.

A side by side comparison of the same patient before and after treatment.

Just a year after the U.S. Food and Drug Administration (FDA) approved the first treatment for severe alopecia areata, the federal agency has approved a second treatment for the disfiguring skin disease — both the result of pioneering research by the same Yale dermatologist.

On June 23, the FDA announced its approval for the use of ritlecitinib — a Janus kinase (JAK) inhibitor — to treat alopecia areata in both adolescents and adults. The medicine, taken orally, goes by the product name Litfulo.

Alopecia areata is an autoimmune disease characterized by sudden, often disfiguring, loss of hair. It is the second most common cause of hair loss, affecting up to 7 million people in the United States.

Dr. Brett King , an associate professor of dermatology at Yale School of Medicine, worked with pharmaceutical company Pfizer to conduct a series of clinical trials with ritlecitinib. He worked with Eli Lilly and Company on clinical trials for the earlier medicine — baricitinib (which goes by the product name Olumiant), approved as a treatment for patients with severe alopecia areata in June 2022 .

King’s groundbreaking work with JAK inhibitors, which were originally designed to treat rheumatoid arthritis and myelofibrosis (a rare blood cancer), has shown significant potential to treat an array of intractable skin diseases, including eczema, erosive lichen planus, vitiligo, granuloma annulare, and sarcoidosis.

King spoke with Yale News about this latest FDA approval.

How does FDA approval for ritlecitinib change the treatment landscape for people with alopecia areata?

Brett King: Ritlecitinib [Litfulo] changes the treatment landscape for people with alopecia areata enormously. Last year, history was made when baricitinib [Olumiant] was FDA approved for the treatment of adults with severe alopecia areata. But alopecia areata affects people of all ages and, indeed, it commonly affects children of all ages. Ritlecitinib is approved in patients ages 12 years and older.

Childhood and adolescence are such vulnerable times, and children and adolescents have so much to do and learn and become during these years. It is challenging enough to be a kid, but when alopecia areata happens and suddenly one has big bald spots or is completely bald and missing eyebrows, the normal trajectory of that kid’s life, and the family’s life, too, can be derailed. Kids withdraw from sports and other social activities, and even from school. Extreme sadness and anxiety are common. It is awful. There is a way out of the darkness, however, and that is to regrow the hair that was lost, to restore the person as they had been prior to alopecia areata.

Normalcy is so important for everybody, but especially when we are developing. So it is easy to understand what a monumental breakthrough it is to have a medicine, ritlecitinib, approved for adolescents. Ritlecitinib restores normalcy and will make life better — literally will change life — for so many people.

When can patients in the U.S. expect ritlecitinib to be available for use?

King: Hopefully in the days or weeks ahead.

You have been at the center of two FDA approvals for major treatments of alopecia areata in two years. Has that sunk in yet — and how does that make you feel?

King: These new medicines for alopecia areata are historic, and I feel super fortunate to be a part of their development. Being a doctor is amazing because I get to share in the lives of others, hopefully making those lives better. It happens one person at a time, though. To have played a central role in the development of treatments for alopecia areata and other diseases — treatments that doctors around the world will give to thousands and thousands (or even millions) of people to make their lives better — is really incredible. We are all a part of something bigger than ourselves, and for me this experience highlights that as well as the possibility that we can change the world.

What are you working on next?

King: The next horizon is approval of these and other treatments for younger patients. Remember, alopecia areata is not uncommon in pre-adolescents. Also, JAK inhibitors do not work for everybody with alopecia areata, and so work needs to be done both to understand why that is and to develop treatments other than JAK inhibitors. The goal is for everybody to be able to have effective treatment. We have come so, so far but we still have a ways to go. It’s exciting.

• New Alopecia Areata treatment aims to help adults and adolescents
• FDA approves alopecia areata treatment with roots at Yale
• New trials for alopecia areata treatment are a success

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• Published: 12 September 2023

Hair loss treatments take aim at the immune system

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Nature Biotechnology volume  41 ,  pages 1179–1181 ( 2023 ) Cite this article

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Drugs commonly used in rheumatology, the JAK inhibitors, are opening up treatment options for people with autoimmune-driven hair loss, and new mechanistic knowledge is also helping scientists tackle androgenic alopecia, the commonest cause of baldness.

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Can we finally reverse balding with these new experimental treatments?

Male pattern baldness could soon be a thing of the past, with new hair loss treatments beginning to show tantalising results

By Joshua Howgego

26 September 2023

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I’LL level with you: a part of me didn’t want to write this story. When I first realised that I was losing my hair, I found it important to mention it often in conversation. I was so embarrassed about it that I was trying some sort of reverse psychology. But I soon realised that if there was one thing less attractive than my balding head, it was how much I was talking about it. I am joking, of course: there is nothing wrong with being bald. Still, for me, the prospect is terrifying. My hair is a big part of my identity, so to lose it is crushing.

I’m not alone. By the age of 50, between 30 and 50 per cent of men have begun to experience male pattern baldness . Despite there being plenty of handsome hairless men out there – I’m looking at you, Thierry Henry – studies suggest that people tend to perceive bald men as less attractive and less friendly . And we don’t need science to tell us that this can be deeply upsetting.

So although I have dialled down the discussion of my growing bald patch, I have been quietly digging into the science of hair loss – and what I found is worth shouting about. It is common knowledge that some treatments can slow hair loss. What is less known is that as we are coming to understand the reasons why male pattern baldness causes people to lose their hair, we are finding new strategies to restore it. There may soon be a way to not just slow balding, but reverse it.

In a field…

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Studies Uncover New Approaches to Combat Hair Loss in Men and Women

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Two recent studies highlight novel ways to combat pattern hair loss in men and women using small molecules such as JAK inhibitors that reawaken dormant hair follicles, as well as stem cell therapies aimed at growing new follicles. 

In the first study, researchers led by Angela Christiano, PhD , the Richard & Mildred Rhodebeck Professor of Dermatology at Columbia University Vagelos College of Physicians and Surgeons, discovered previously unknown cells that keep mouse hair follicles in a resting state and show that inhibiting the activity of these cells can reawaken dormant follicles.

In a second study, Christiano’s team created a way to grow human hair in a dish , which could open up hair restoration surgery to more people, including women, and improve the way pharmaceutical companies search for new hair-growth drugs.

Study Discovers Cells That Put Hair Follicles to Sleep

Cross section of a hair follicle. Image: Angela Christiano / Columbia University Irving Medical Center.

In male and female pattern baldness, many hair follicles still exist but are dormant. The search for new drugs that reawaken follicles and induce hair growth has been limited by the field’s focus on finding drugs that work along the same pathways as finasteride and minoxidil, the only two drugs currently available for men with male pattern baldness. 

Christiano and her colleagues previously discovered a new pathway, called JAK-STAT, that is active inside the stem cells of resting hair follicles and keeps them in a dormant state. They previously demonstrated that JAK inhibitors applied to mouse skin are a potent way to reawaken resting hair follicles in mice. 

In their latest study, the researchers wanted to get a detailed picture of the natural processes that keep follicles dormant, so they looked for factors that controlled the JAK pathway activity in the hair follicle. 

New Cells Called Trichophages

The search revealed a previously unknown immune-related cell type that produces a substance known as Oncostatin M that keeps the follicles in a state of dormancy. “Rare subsets of immune cells were previously difficult to identify in whole skin, but this work was facilitated by our ability to sequence individual cells and pinpoint the ones making Oncostatin M,” says Etienne Wang, PhD, first author of the study. These cells are most similar to macrophages, which are scavenger cells of the immune system, and the team found them in close association with resting hair follicles.

The researchers named these cells trichophages, after the Greek word tricho for hair.

Targeting the trichophages can also turn on the hair cycle. By using small molecule inhibitors and antibodies to block Csf1R, a receptor on the trichophages, the researchers could block the flow of Oncostatin M and restart the hair cycle. 

Reawakening Dormant Hair Follicles with New Drugs

“Our previous studies implicated JAK-STAT signaling as one potential new therapeutic pathway for hair loss disorders by targeting hair follicle stem cells with JAK inhibitors,” Christiano says. (A biotech company recently reported results of a small phase 2 trial of a topical JAK-STAT inhibitor based on these studies.) “Here, we show that blocking the source of the JAK activating signal outside the hair follicle is another way to target this mechanism.”

Most drug development has focused on treatments for male pattern hair loss, and the majority of clinical trials are conducted exclusively in men.  

“These new pathways may lead to new treatments for both men and women suffering from hair loss, since they appear to be acting independently of male hormone pathways,” Christiano says. “Especially if treatments are used topically, that could avoid the related side effects seen with finasteride and minoxidil.”

Growing New Hair Follicles in a Dish

In a second study, aimed at using stem cells for hair growth, the Columbia researchers have created a way to grow human hair in a dish, which could open up hair restoration surgery to more people, including women, and improve the way pharmaceutical companies search for new hair growth drugs.

It is the first time that human hair follicles have been entirely generated in a dish, without the need for implantation into skin.

Using 3D-Printing to Stop Hair Loss

For years it’s been possible to grow mouse or rat hairs in the lab by culturing cells taken from the base of existing follicles. 

“Cells from rats and mice grow beautiful hairs,” Christiano says. “But for reasons we don’t totally understand, human cells are resistant.”

To break the resistance of human hair cells, Christiano has been trying to create conditions that mimic the 3D environment human hair cells normally inhabit. The lab first tried creating little spheres of cells inside hanging drops of liquid. But when the spheres were implanted in mice, the results were unpredictable: The cells from some people created new hair while others didn’t.

3D Printing Creates Patterned Hair Follicles

In the new study, Christiano’s team exploited the unique capability of 3D printers to create a more natural microenvironment for hair follicle growth. 

The researchers used 3D printing to create plastic molds with long, thin extensions only half a millimeter wide. “Previous fabrication techniques have been unable to create such thin projections, so this work was greatly facilitated by innovations in 3D printing technology,” says Erbil Abaci, PhD, first author of this study. 

After human skin was engineered to grow around the mold, hair follicle cells from human volunteers were placed into the deep wells and topped by cells that produce keratin. The cells were fed a cocktail of growth factors spiked with ingredients, including JAK inhibitors, that the lab has found stimulates hair growth. 

After three weeks, human hair follicles appeared and started creating hair.

Hair Farms Could Expand Availability of Hair Restoration

Though the method needs to be optimized, engineered human hair follicles created in this way could generate an unlimited source of new hair follicles for patients undergoing robotic hair restoration surgery.

Hair restoration surgery requires the transfer of approximately 2,000 hair follicles from the back of the head to the front and top. It is usually reserved for male patients whose hair loss has stabilized and who have enough hair to donate.

“What we've shown is that we can basically create a hair farm: a grid of hairs that are patterned correctly and engineered so they can be transplanted back into that same patient's scalp,” Christiano says. 

“That expands the availability of hair restoration to all patients—including the 30 million women in the United States who experience hair thinning and young men whose hairlines are still receding. Hair restoration surgery would no longer be limited by the number of donor hairs.”

The engineered follicles also could be used by the pharmaceutical industry to screen for new hair growth drugs. Currently, high throughput screening for new hair drugs has been hampered by the inability to grow human hair follicles in a lab dish. No drugs have been found by screening; the only two approved for the treatment of pattern hair loss—finasteride and minoxidil—were initially investigated as treatments for other conditions.  

The team hopes that cultured hair farms will open up the ability to perform high throughput drug screens to identify new pathways that influence hair growth.

The first study, titled “ A Subset of TREM2+ Dermal Macrophages Secretes Oncostatin M to Maintain Hair Follicle Stem Cell Quiescence and Inhibit Hair Growth ,” was published in Cell Stem Cell.

Other authors: Etienne C.E. Wang (Columbia University Irving Medical Center and National Skin Center, Singapore), Zhenpeng Dai (CUIMC), Anthony W. Ferrante (CUIMC), and Charles G. Drake (CUIMC).

The research was supported by the National Skin Center of Singapore, the National Medical Research Council of Singapore, the Locks of Love Foundation, and the National Institutes of Health (S10OD020056, P30AR069632, and P50AR070588).

Dr. Christiano is a consultant and shareholder for Aclaris Therapeutics Inc., a consultant for Dermira Inc., and recipient of grant funding from Pfizer Inc. Dr. Drake has served as a paid consultant for Agenus, Bayer, BMS, F-Star, Janssen, Merck, Pfizer, Pierre Fabre, Roche/Genentech, and Shattuck Labs. He has ownership interest in Compugen, Harpoon, Kleo, Potenza, Tizona, and Werewolf.

Columbia University has licensed intellectual property related to these studies to Aclaris Therapeutics Inc. 

The second study, titled “ Tissue engineering of human hair follicles using a biomimetic developmental approach ,” was published in Nature Communications. 

Other authors: Hasan Erbil Abaci, Abigail Coffman, Yanne Doucet, James Chen, Joanna Jacków, Etienne Wang, Zongyou Guo, Jung U. Shin (all from Columbia University Vagelos College of Physicians and Surgeons) and Colin A. Jahoda (Durham University, Durham, U.K.).

The research was supported by the NIH (National Center for Advancing Translational Sciences grant UH2EB017103; National Institute of Arthritis and Musculoskeletal and Skin Diseases grants K01AR072131 and P30AR069632); New York State Stem Cell Science (SDH C029550); an Ines Mandl Research Foundation Fellowship; and a CUIMC Precision Medicine Research Fellowship (with funds from NIH grant  UL1TR001873 ).

Dr. Christiano and Dr. Jahoda are founders of Rapunzel Bioscience Inc., which focuses on developing regenerative therapies for skin and hair disorders. The remaining authors declare no competing interests.

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An updated etiology of hair loss and the new cosmeceutical paradigm in therapy: clearing ‘the big eight strikes’.

1. Introduction

1.1. reversible autoimmune: alopecia areata, 1.2. androgenetic: androgenetic alopecia (aga: pattern hair loss), 1.2.1. dihydrotestosterone (dht), 1.2.2. molecular mechanisms of dht, 1.2.3. finasteride as a 5α-reductase inhibitor, 1.2.4. beyond dht, 1.3. scarring: cicatricial/fibrosing alopecia, 1.4. fungal/bacterial alopecia: follicular decalvans and tinea capitis, 1.5. stress/trauma (chemical, psychological, and physical), 2. the big eight strikes, in simple terms, 2.1. imbalance of androgens (dht, testosterone, and shbg) in cases of androgenetic alopecia, 2.2. imbalance of prostaglandins (pgf 2 -α, pgd 2 ), 2.3. overactive sebum production and sugar metabolism, 2.4. bacterial and fungal overgrowth, 2.5. micro-inflammation, 2.6. micro-scarring and collagen, 2.7. inefficient circulation and metabolism, 2.7.1. circulation, 2.7.2. metabolism, 2.8. nutrient deficiency, 3. clearing the big eight strikes with cosmeceuticals to improve hair, 3.1. strike 1: imbalance of androgens, 3.2. strike 2: imbalance of prostaglandins, 3.3. strike 3: sebum and sugar metabolism, 3.4. strike 4: bacterial and fungal overgrowth, 3.5. strike 5: micro-inflammation, 3.6. strike 6: micro-scarring and collagen, 3.7. strike 7: inefficient circulation and metabolism, 3.8. strike 8: nutrient deficiency, 4. critical examination of a selection of exemplary cosmeceuticals in the market, 4.1. redensyl tm ingredients, 4.2. capixyl tm ingredients, 4.3. anasenzyl ® ingredients, 4.4. procapil ® ingredients, 4.5. anagain tm ingredients, 4.6. concentration, clinical efficacy, and combining the proprietary blends, 5. conclusions.

• Imbalance of androgens (DHT, testosterone, and SHBG) in cases of androgenetic alopecia: DHT triggers the expression of TGF-β1, which is reciprocal to the canonical Wnt signaling pathway.
• Imbalance of prostaglandins (PGF 2 -α, PGD 2 ): Depletion of NADPH redirects the biosynthesis of prostaglandins toward PGD 2 . This may be jointly caused by bacterial overgrowth of P. acnes and the polyol pathway.
• Overactive sebum production and sugar metabolism: Prostaglandins and the polyol pathway change the metabolism of sugar so that lipid is produced in favor of glycogen stores; this may be due to increased expression of AKR1B1, a substrate for prostaglandin synthesis, and a trigger of the polyol pathway; insulin-like growth factor 1 is under-expressed in the balding scalp, and this may be why the glycogen stores are depleted.
• Bacterial and fungal overgrowth: Scalps afflicted with hair loss generally have bacterial overgrowth or inflammatory infiltrates as byproducts of clearing microbes. The bacteria can be P. acnes or S. aureus (in cases of scarring alopecia). The fungus is M. furfur.
• Micro-inflammation: Inflammation in the balding scalp can be severe, such as in scarring alopecia, or it can be low-grade chronic, such as in AGA. The term micro-inflammation was coined because candidates are unaware of the inflammation in AGA; it is subtle.
• Micro-scarring and collagen: While therapies can halt the progression of fibrosis, it is difficult to reverse it. The best approach is via the use of biomimetic peptides that signal a restructuring of the dermis and promote a return of the stem cell niche.
• Inefficient circulation and metabolism (i.e., cholesterol and scalp tension): Circulation is two-fold. It involves the transport of nutrients to the scalp, and it is equally as important to transport waste out. The elimination of waste can be antagonized by the inactivity of metabolizing enzymes that are responsible for converting waste into soluble forms, such as the metabolism of cholesterol.
• Nutrient deficiency (or nutrient synthesis via metabolism, i.e., vitamin D): Nutrient deficiencies can be corrected with supplementation, but the benefit can also be experienced by supplementing an item in the absence of a deficiency of that item, such as by the addition of amino acids to the diet. Furthermore, a deficiency can be caused by a failure of local metabolic processes that create nutrients, such as vitamin D, which can be adequate in terms of dietary intake but is not being utilized by hair follicles in balding scalps.

Author Contributions

Institutional review board statement, informed consent statement, data availability statement, acknowledgments, conflicts of interest.

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Share and Cite

Sadgrove, N.; Batra, S.; Barreto, D.; Rapaport, J. An Updated Etiology of Hair Loss and the New Cosmeceutical Paradigm in Therapy: Clearing ‘the Big Eight Strikes’. Cosmetics 2023 , 10 , 106. https://doi.org/10.3390/cosmetics10040106

Sadgrove N, Batra S, Barreto D, Rapaport J. An Updated Etiology of Hair Loss and the New Cosmeceutical Paradigm in Therapy: Clearing ‘the Big Eight Strikes’. Cosmetics . 2023; 10(4):106. https://doi.org/10.3390/cosmetics10040106

Sadgrove, Nicholas, Sanjay Batra, David Barreto, and Jeffrey Rapaport. 2023. "An Updated Etiology of Hair Loss and the New Cosmeceutical Paradigm in Therapy: Clearing ‘the Big Eight Strikes’" Cosmetics 10, no. 4: 106. https://doi.org/10.3390/cosmetics10040106

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• People Tested

The 6 Best Hair Loss Treatments of 2024, Tested by People with Thinning Hair

Our top pick is the Advanced Trichology NutraM DHT Blocking Hair Serum

Jessie Quinn is a Los Angeles-based contributing shopping writer at PEOPLE with over 10 years of experience covering all things beauty, fashion, and lifestyle. At PEOPLE, she collaborates with the PEOPLE Tested team to share our top recommendations for everything from the best shapewear to the best dark spot correctors.

In This Article

• Our Top Picks
• What to Know

Behind The Scenes

Why trust people.

• What Is PEOPLE Tested?

People / Taylor Calta

If your hair seems thinner than usual, you're not alone: 50 percent of women and 80 percent of men experience hair loss in their lifetime. But thanks to impressive hair loss treatments designed to thicken up your ‘do while also shielding against hair-thinning hormones, you can put an end to excessive hair fall and even help your hair grow back .

The More You Know

Since there are so many causes of hair loss, treatment results can differ person to person. And while they might not solve the issue altogether, board-certified dermatologist Dr. Dendy Engelman says individuals experiencing hair loss caused by factors like genetics, hormonal imbalances, or lifestyle choices can still benefit from hair loss treatments.

With so many different hair care products that claim to make your hair thicker and longer, finding one that actually does the trick takes time, research, and resources. Our PEOPLE Tested team dedicated nearly 1,000 hours testing 20 formulas and uncovered which treatments were effective and, ultimately, worth the money.

Best Overall

Advanced trichology topical melatonin hair growth serum.

Advanced Trichology

Easy to apply

Quick-drying and not greasy

Saw hair growth after one month

Excellent value

Has a strong scent

After testing 20 hair loss treatments, this serum received top marks and was a clear winner for top spot. The dropper makes application super easy (you can apply it directly to the scalp) and the quick-drying formula is never greasy so it doesn’t mess up your hairstyle or require extra washing. It absorbed easily and never caused irritation.

When testing this hair loss treatment, we noticed results within just one month of use . At the end of the testing period, our hair looked and felt a lot thicker, with new growth in some of the thinner areas as well as along our hairline.

Ingredients: Melatonin, minoxidil | Size: 2 ounces | Supply: 90 days

Best Overall (Cheaper)

Hers minoxidil foam for women.

Comes in 2, 4, and 6-month supplies

Costs around $15 per month

A little goes a long way

Saw results in one month

Hard to clean the cap after using

For another quick-acting hair loss treatment, we also loved the Minoxidil Foam from hers. This treatment comes in 2-, 4-, and 6-month supplies and costs around $15 per month (the 4- and 6-month plans are even cheaper). It has a mousse-like consistency that is easy to work into the scalp and doesn’t interfere with style, though there is a little bit of a sheen upon application.

After just one month of testing, we began to see a difference in our root growth. At the end of the testing period, our hair looked and felt a lot thicker and healthier . It also has a soothing and cooling touch that feels nice on irritated scalps and is scent-free so it’s great for sensitive noses. 

Ingredients: Minoxidil | Size: 2.11 ounces | Supply: 2-6 months

People / Alexa Jade Frankelis

Easiest Application

Keranique hair regrowth treatment.

Easy to target specific areas

Doesn’t leave hair greasy

Saw results after two months

Takes a little longer to absorb and dry

As much as we love the Advanced Trichology NutraM DHT Blocking Hair Serum for its application process, we found that this solution from Keranique was even easier to use. The serum features applicator caps with long nozzles that apply directly to the scalp, making it less messy and easier to target specific areas versus the entire head. It takes a little longer to absorb and dry (around five minutes), but it doesn't dry greasy.

While we didn’t see results as quickly as some of the other formulas on our list, we still noticed improvements before the end of the testing period. After around eight weeks, our hair looked and felt a lot thicker and we noticed new growth in some of the sparser areas of our scalp . 

Ingredients: Minoxidil | Size: 2 ounces | Supply: 60 days

People / Allison Vancura

Best for Men

Nioxin 5% minoxidil hair regrowth treatment for men.

Quick to absorb and dry

Noticeable results after nine weeks

Improved bald spot hair growth

Messy application process

Not ideal for sensitive scalps

This serum from Nioxin is the best hair loss treatment for men. We tested this on a bald spot, and after nine weeks of twice daily use some baby hairs started to sprout . The scalp serum features a dropper that is relatively easy to use but can get a bit awkward when targeting a specific area, especially on the back of the head.

While it absorbs quickly, the serum is a bit runny which can make for a messy application process (this formula in spray form would have been much more ideal). Nonetheless, we were impressed by the regrowth and think it’s worth using over a longer period of time to maximize the hair growth benefits. 

Ingredients: Minoxidil | Size: 2 ounces | Supply: 30 days

Best for Color-Treated Hair

Virtue minoxidil 5% hair growth treatment.

Virtue Labs

It comes with shampoo, conditioner, and treatment

Available in 30 and 90 days supply

Less hair fall

If want a hair loss treatment that won’t interfere with your color-treated hair , try this regimen from Virtue. The kit comes with hair loss shampoo , conditioner, and a minoxidil treatment designed to support hair growth. Despite using the product just every two weeks, we still experienced growth along the hairline and our strands felt a lot thicker with less fall, too. 

Ingredients: Minoxidil, gamma keratin, alpha keratin | Size: Varies, depending on product | Supply: 30-90 days

People / Chantia Murphy

Best Thickening

Rogaine women's 2% minoxidil topical solution hair regrowth treatment.

Only takes seconds to absorb

Hair looked thicker and longer after 6 weeks

Doesn’t have a greasy residue

Messier application process

Whether you have experienced some fall or want to thicken up your strands, this treatment from Rogaine is worth considering for its thickening benefits. The minoxidil-infused formula absorbs into the scalp within seconds and doesn’t leave the roots feeling greasy or fade color-treated hair. It’s also one of the more efficient formulas we tried, as we noticed thicker and longer hair after just six weeks of use. 

People / Alisa Hale

What to Know About Hair Loss Treatments

Ingredients.

Dr. Engelman says to look for hair growth promoters like minoxidil , biotin , and keratin , as these can promote regeneration and strengthen hair. “Scalp treatments containing ingredients like caffeine or palmetto can also block the effects of dihydrotestosterone (DHT), a hormone associated with hair thinning,” she says.

All six treatments on our list contain minoxidil for growth, including our top pick for the best hair loss treatment, the Advanced Trichology NutraM DHT-Blocking Hair Serum (90-Day Supply) . If you want something with some extra oomph, the Virtue Hair Growth Treatment also has gamma and alpha keratin to strengthen strands and improve growth efforts. 

Long-Term Use 

While there are some hair styling products that can create the illusion of thicker, fuller hair, there is no such thing as an overnight solution for hair loss. When adding hair loss treatments to your regimen, Dr. Jacobs says to use them consistently and long-term for best results.

With that said, if you are hoping to achieve some noticeable improvements in a shorter amount of time, we found that the Advanced Trichology NutraM DHT-Blocking Hair Serum made our hair thicker after just one month of regular application (though of course, results were more noticeable after a longer testing period). 

Underlying Causes of Hair Loss

Hair loss treatments can help improve thickness and length with regular use. However, Dr. Jacobs and Dr. Engelman both express the importance of knowing the underlying cause of your loss and working with a medical professional to help address the concern.

“Hair loss can be the result of various factors, including hormonal fluctuations (such as pregnancy and postpartum), genetic predispositions, aging, stress, and seasonal changes,” says Dr. Jacobs. 

Vitamin and mineral deficiencies can also lead to hair loss, especially if you have lower levels of iron, vitamin B12, vitamin D, and biotin. “Lack of these nutrients might cause hair thinning or shedding because they are essential for sustaining healthy hair growth,” says Dr. Engelman. “Vitamin D affects the hair growth cycle by inhibiting the proliferation of hair follicle cells, and iron deficiencies can lead to anemia causing reduced oxygen delivery to the hair follicles and subsequent hair loss.” Dr. Engelman says biotin is also important because it is essential for the production of keratin, which is the protein that makes up the hair shaft. 

Additionally, Dr. Engelman says environmental factors “like exposure to pollutants or harsh chemicals in hair care products can damage the hair follicles,” which can result in hair loss over time. 

By addressing the underlying causes of hair loss and using a treatment regularly in your regimen, you can begin to reverse the side effects and achieve desired results. 

We researched dozens of formulas before taking 20 products out for a real-world spin. We spent 12 weeks and 960 hours testing each treatment, carefully considering the application process, effectiveness, and overall results.

• Application: During the testing period, we considered the packaging and required application process to get a general idea of convenience. We carefully looked at the applicator itself, plus the required treatment time, usage, and amount required to achieve desired results. We also made note of ease-of-use, the consistency, and if the process was messy or not. 
• Effectiveness: When using a hair loss treatment, you of course want it to be effective. Witht his in mind, we marked down which formulas gave us the best results, how long it took to experience said results, and if the products matched their claims. We also considered which ones worked best for thickening and which ones promoted growth. 
• Overall Results: After considering the application process and effectiveness, we compared our notes and looked at the overall results of all 20 formulas. In addition to the hair growth outcomes, we also considered which formulas had the best absorption, were quick-drying, and didn’t leave behind any greasy residue. 

Once our results were in, we compared and rated each product before narrowing down our selection to these six best hair loss treatments on the market.

Jessie Quinn is a contributing commerce writer for PEOPLE and has written for publications such as Byrdie, InStyle, The Spruce, NYLON, and more. Jessie has spent years trying to improve her hair health and promote growth. While she might have long and healthy strands today, she’s gone through phases of hair loss and has tried everything from supplements to serums to achieve her current ‘do. 

She considered her own experiences as well as those of our PEOPLE Tested team to highlight the formulas that are worth spending your energy and money on. Jessie also reached out to board-certified dermatologists Dr. Michael I. Jacobs and Dr. Dendy Engelman to learn more about what causes hair loss and what to look for in effective treatments.

Our Expert Panel

• Dr. Michael I. Jacobs is a board-certified dermatologist and associate professor of dermatology at Weill Cornell Medical College.
• Dr. Dendy Engelman is a board-certified cosmetic dermatologist and Mohs surgeon Shafer Clinic in New York City.

What Is PEOPLE Tested? 

We created the PEOPLE Tested seal of approval to help you find the very best products for your life. We use our unique methodology to test products in three labs across the country and with our network of home testers to determine their effectiveness, durability, ease of use, and so much more. Based on the results, we rate and recommend products so you can find the right one for your needs.

But we don’t stop there: We also regularly re-review the categories in which we’ve awarded the PEOPLE Tested seal of approval — because the best product of today might not be the best of tomorrow. And by the way, companies can never buy our recommendation: Their products must earn it, fair and square.

In short, PEOPLE Tested provides recommendations you can trust — every day, every purchase.

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FDA Approves New Medication for Chronic Weight Management

FDA News Release

Today, the U.S. Food and Drug Administration approved Zepbound (tirzepatide) injection for chronic weight management in adults with obesity (body mass index of 30 kilograms per square meter (kg/ m2) or greater) or overweight (body mass index of 27 kg/m2 or greater) with at least one weight-related condition (such as high blood pressure, type 2 diabetes or high cholesterol) for use, in addition to a reduced calorie diet and increased physical activity. Tirzepatide, the active ingredient in Zepbound, is already approved under the trade name Mounjaro to be used along with diet and exercise to help improve blood sugar (glucose) in adults with type 2 diabetes mellitus.

“Obesity and overweight are serious conditions that can be associated with some of the leading causes of death such as heart disease, stroke and diabetes,” said John Sharretts, M.D., director of the Division of Diabetes, Lipid Disorders, and Obesity in the FDA’s Center for Drug Evaluation and Research. “In light of increasing rates of both obesity and overweight in the United States, today’s approval addresses an unmet medical need.” 

Approximately 70% of American adults have obesity or overweight, and many of those overweight have a weight-related condition. Losing 5% to 10% of body weight through diet and exercise has been associated with a reduced risk of cardiovascular disease in adults with obesity or overweight.

Zepbound activates receptors of hormones secreted from the intestine (glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)) to reduce appetite and food intake. Zepbound is administered by injection under the skin once weekly, and the dosage must be increased over four to 20 weeks to achieve the target dosages of 5 milligram (mg), 10 mg or 15 mg once weekly. The maximum dosage of Zepbound is 15 mg once weekly.

Zepbound’s effectiveness for chronic weight management (weight reduction and maintenance) in combination with a reduced-calorie diet and increased physical activity was established in two randomized, double-blind, placebo-controlled trials of adults with obesity or overweight with at least one weight-related condition. These studies measured weight reduction after 72 weeks in a total of 2,519 patients who received either 5 mg, 10 mg or 15 mg of Zepbound once weekly and a total of 958 patients who received once-weekly placebo injections. In both trials, after 72 weeks of treatment, patients who received Zepbound at all three dose levels experienced a statistically significant reduction in body weight compared to those who received placebo, and greater proportions of patients who received Zepbound achieved at least 5% weight reduction compared to placebo.   The larger of the two trials enrolled adults without diabetes. At the start of the trial, the average body weight was 231 pounds (105 kg) and average body mass index was 38 kg/m2. In this trial, those randomized to receive the highest approved dosage of Zepbound (15 mg once weekly) lost on average 18% of their body weight compared to those randomized to placebo. 

At the start of the trial in adults with type 2 diabetes, the average body weight was 222 pounds (101 kg) and average body mass index was 36 kg/m2. Those randomized to receive the highest approved dosage of Zepbound (15 mg once weekly) lost on average 12% of their body weight compared to those randomized to placebo.

Zepbound can cause side effects such as nausea, diarrhea, vomiting, constipation, abdominal (stomach) discomfort and pain, injection site reactions, fatigue, hypersensitivity (allergic) reactions (typically fever and rash), burping, hair loss and gastroesophageal reflux disease.

Zepbound causes thyroid C-cell tumors in rats. It is unknown whether Zepbound causes such tumors, including medullary thyroid cancer, in humans. Zepbound should not be used in patients with a personal or family history of medullary thyroid cancer or in patients with Multiple Endocrine Neoplasia syndrome type 2. 

Zepbound has not been studied in patients with a history of pancreas inflammation (pancreatitis) or severe gastrointestinal disease (including severe gastroparesis, a condition that affects normal movement of the muscles in the stomach). It should not be used in combination with Mounjaro or a GLP-1 receptor agonist. The safety and effectiveness of coadministration of Zepbound with other medications for weight management have not been established. 

Zepbound should not be used in patients with a history of severe allergic reaction to tirzepatide (its active ingredient) or to any of its other ingredients. Patients should stop Zepbound immediately and seek medical help if a severe allergic reaction is suspected. Zepbound also contains warnings for inflammation of the pancreas (pancreatitis), gallbladder problems, hypoglycemia (blood sugar that is too low), acute kidney injury, diabetic retinopathy (damage to the eye’s retina) in patients with type 2 diabetes mellitus and suicidal behavior or thinking. Patients should discuss with their health care provider if they have symptoms of pancreatitis or gallstones. If Zepbound is used with insulin or a medication that causes insulin secretion, patients should speak to their health care provider about potentially lowering the dose of these other medicines to reduce the risk of hypoglycemia. Health care providers should monitor patients with kidney disease, diabetic retinopathy and depression or suicidal behaviors or thoughts. 

Zepbound received Priority Review and Fast Track designations for this indication.

The FDA granted this approval to Eli Lilly and Co.

Related Information

• NIH: Overweight & Obesity Statistics

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, radiation-emitting electronic products, and for regulating tobacco products.

Benny Gantz resigns from Israel war Cabinet and some doctors caution over hair loss drug: Morning Rundown

Netanyahu rival resigns from Israel’s war Cabinet saying the prime minister stands in the way of “real victory.’’ Some doctors caution about a common men’s hair loss drug. And Trump is expected to attend a probation hearing. 

Here’s what to know today.

Gantz quits Israeli war Cabinet after hostage rescue operation left hundreds of Palestinians dead

Joy in Israel over the rescue of four hostages has given way to the harsh realities of the bloody war in Gaza that has dragged on for nine months and whose deep divisions remained largely unchanged by the successful operation.

The operation on Saturday resulted in the rescue of four hostages, among them Noa Argamani, whose abduction on Oct. 7 during the Nova music festival was captured on video. But it came at the cost of hundreds of Palestinian lives. As of Sunday, Gaza’s Health Ministry said that at least 270 people were killed and another 700 were injured, marking one of the bloodiest days in the war . More people are believed to be buried in the rubble.

This is Morning Rundown, a weekday newsletter to start your day. Sign up here to get it in your inbox.

Yesterday, Benny Gantz announced his resignation from Israel’s war Cabinet. Gantz, a key rival of Israeli Prime Minister Benjamin Netanyahu, said he was quitting after a postwar plan for the Palestinian enclave of Gaza failed to materialize. In a televised event, Gantz said that Netanyahu stood in Israel’s way to “a real victory,” and he apologized to the families of hostages, saying “we failed” to bring most of them home. Read more about the tensions that preceded Gantz’s resignation.

More Israel-Hamas war coverage:

• Secretary of State Antony Blinken is set to visit the Middle East today. His effort to achieve a cease-fire agreement between Israel and Hamas was likely complicated by the rescue operation, a senior Biden administration official said. Here’s why.
• Biden administration officials have discussed potentially negotiating a unilateral deal with Hamas to secure the release of five American hostages if the current cease-fire talks involving Israel fail, according to two current and two former senior U.S. officials. 

Macron announces snap legislative election

President Emmanuel Macron is leaving France’s political fate in the hands of voters after a surprise decision over the weekend to dissolve the lower house of the country’s parliament. The move came after his party was handed a humbling defeat by the far right in the European Union’s parliamentary elections on Saturday. The projected results showed Marine Le Pen’s far-right, anti-immigration National Rally party well ahead of Macron’s centrist, pro-European Renaissance party, according to French opinion poll institutes.

In making this decision, Macron is taking a big risk with a move that could backfire. If an opposition party wins a parliament majority, it could lead to a fraught power-sharing situation called “cohabitation,” that would force Macron to name a prime minister with different views. Macron’s term as president still runs for three more years. The legislative elections will take place in two rounds on June 30 and July 7. Here’s what else to know about Macron’s decision.

Trump to attend probation hearing today

Donald Trump is scheduled to sit down for a virtual interview today with a New York City probation officer, a requirement by the court after the former president was found guilty on all counts in his hush money trial. Three sources familiar with the matter said the interview will be from his home at Mar-a-Lago with his attorney Todd Blanche at his side, done over a special virtual network with added security measures.

While legal experts noted that a probation interview over a video conference call is unusual, having a former president in a New York probation office would also be unprecedented. Here’s what Trump could be asked about during the interview.

More Donald Trump coverage:

• After his guilty verdict, Trump is focused on revenge.  Just look at his recent interviews  with Sean Hannity and Dr. Phil.

A ‘last chance’ parole hearing for Leonard Peltier

Native American activist and federal prisoner Leonard Peltier, who has maintained his innocence in the murders of two FBI agents almost half a century ago, is due for a full parole hearing today. It’s his first in 15 years — and it may be the 79-year-old’s last chance to advocate for his release, his supporters fear.

Peltier was part of a gunfight that resulted in the deaths of the two FBI agents on the Pine Ridge Reservation in South Dakota in 1975. There has been decades of scrutiny surrounding how his case was investigated and how the trial was conducted. Peltier’s attorney argues that his client’s age, declining health and nonviolent record in prison should be accounted for as the commission decides whether to grant parole. 

But Peltier faces a layered hearing process , and the FBI remains “resolute” in its opposition to Peltier’s release.

As more young men use a hair loss drug, some doctors caution about rare side effects

More young men are taking a medication to prevent hair loss, prompting some concerns that the oral drug has been linked to rare but potentially long-lasting side effects. A report conducted on behalf of NBC News found that the number of men in the U.S. with finasteride prescriptions increased nearly 200% in the last seven years.

“It’s like water in my clinic,” a NYC dermatologist said. “I’m prescribing it all the time.”

Doctors say the daily pill is safe, although once someone starts taking it, they’ll need to continue for as long as they want to avoid hair loss. But there’s some controversy about the drug, due to the possibility of impotence that could last even after stopping the medication, along with other side effects that users have reported.

Politics in Brief 

Abortion rights: The Supreme Court is set to rule this month on two major abortion cases for the first time since Roe v. Wade was overturned — one about the abortion pill mifepristone and the other about a near-total ban on abortion care in Idaho. Supreme Court reporter Lawrence Hurley explains what’s at stake in the two cases.

Biden in France: Without speaking Trump’s name, President Joe Biden sought to draw contrast with his Republican rival throughout his five days in France. The trip culminated in a visit to a cemetery rich with political symbolism .

Want more politics news? Sign up for From the Politics Desk to get exclusive reporting and analysis delivered to your inbox every weekday evening.  Subscribe here.

Staff Pick: It’s giving camp

From a program for Christian youths on a lake in Minnesota to a refuge for transgender and gender-nonconforming teens in Ohio, summer camps geared specifically toward young LGBTQ people can be found across the country. We talked to founders and campers at three such places about what they offer LGBTQ youths beyond bonfires and nature hikes. —  Brooke Sopelsa,  NBC OUT editorial director

In Case You Missed It

• A “catastrophic” landslide caused the collapse and closure of Teton Pass , a critical roadway between Wyoming and Idaho.
• Four people were hospitalized after a bull escaped an arena at an Oregon rodeo and charged into patrons outside, authorities said yesterday.
• WNBA rookie Caitlin Clark said she has “no disappointment” over being left off the women’s national team for the 2024 Paris Olympics.
• The suspect in a 2022 mass shooting in California was found dead in his jail cell on Saturday.
• The internet is assigning unusual labels to men again. This time, “hot rodent” men are apparently in season.

NBC Select: Online Shopping, Simplified 

If you pop your pimples, just know that the area between your nose and the corners of your mouth is sometimes called the “triangle of death.”  Here’s why.  And instead of popping, try  these acne spot treatments , tested by NBC Select editors. 

Sign up to The Selection  newsletter for hands-on product reviews, expert shopping tips and a look at the best deals and sales each week.

Thanks for reading today’s Morning Rundown. Today’s newsletter was curated for you by Elizabeth Robinson. If you’re a fan, please send a link to your family and friends. They can sign up here .

Elizabeth Robinson is a newsletter editor for NBC News, based in Los Angeles.

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• v.2021; 2021

A Multimodal Hair-Loss Treatment Strategy Using a New Topical Phytoactive Formulation: A Report of Five Cases

Sanusi umar.

1 Department of Medicine, Dermatology Division, University of California at Los Angeles, Los Angeles, CA, USA

2 Division of Dermatology, Harbor-UCLA Medical Center, Torrance, CA, USA

3 Dr. U Hair and Skin Clinic, Manhattan Beach, CA, USA

Marissa J. Carter

4 Strategic Solutions, Inc., Bozeman, MT, USA

Associated Data

In addition to photographic evidence showing interval changes that appear in the manuscript, complete medical records of the presented cases are stored in the treating clinic, in line with the standard of care.

Introduction . Current approved medications for hair loss, such as topical minoxidil and oral finasteride, may have suboptimal efficacy or side effects precluding continued use in some patients. Thus, we report an evaluation of the efficacy, safety, and tolerability of a new topical botanical formulation -GASHEE containing over 12 phytoactive ingredients that affect multiple targets in the cascade of pathophysiologic events that cause hair loss. Five patients with various hair-loss conditions, including cases of previous treatment failures, are presented. Case Presentation . This is a case series of four women and one man with hair loss due to various causes, four of whom had failed minoxidil treatment for over a year. All patients used the topical treatment as a sole therapy for at least 3 months before the documentation of outcomes, which involved interval changes noted through each patient's account, direct observation, and photography. Discussion . In all patients, we observed significant improvements in hair regrowth in the nape, crown, vertex, and temple areas after 3–15 months of treatment. All patients were highly satisfied with their results and reported no adverse events. Although the use of botanicals in the treatment of hair loss is in an infant stage, the new formulation used in this study demonstrated a good efficacy related to hair growth, warranting further evaluation.

1. Introduction

Androgenetic alopecia (AGA, also called male and female pattern alopecia) is the most common cause of hair loss and is estimated to affect 30–58% of men by age 50 and 12–40% of women depending on age and race [ 1 – 4 ]. It is characterized by progressive hair follicular miniaturization caused by the actions of androgens on epithelial cells of genetically susceptible hair follicles in androgen-dependent areas [ 5 ]. While complex genetic inheritance and age of the individual are major risk factors in AGA development, on a cellular level, the initiation of an inflammatory condition in the follicle microenvironment is considered the central event, with contributory mechanisms, including abnormal signal transduction (the wingless-type integration site pathway), high levels of apoptosis, and oxidative stress [ 6 – 11 ]. This supports the need for a multifaceted approach for the treatment of AGA, managing central causes, such as 5-dihydrotestosterone (DHT), oxidative stress, and inflammation, as well as downstream factors that precipitate hair loss by adversely affecting hair stem cells and hair cycles ( Figure 1 ). For instance, DHT, a major factor causing hair loss in AGA, has been found to act downstream by inducing the production of interleukin- (IL-) 6 and transforming growth factor- (TGF-) β 2 by dermal papilla cells (DPCs), thus suppressing hair growth and premature onset of the catagen phase [ 12 , 13 ].

The hair follicle cycle showing the effects of various cytokines, growth promoters, and growth inhibitors regarding different stage transitions. BDNF, brain-derived neurotrophic factor; BMP-2/4, bone morphogenetic protein-2/4; col 17 A1, collagen-type XVII α 1 chain; DKK, Dickkopf-related protein; FGF5/7/18, fibroblast growth factor 5/7; GDNF, glial cell line-derived neurotrophic factor; HGF, hepatocyte growth factor; IGF-1, insulin-like growth factor-1; IL-1/6, interleukin-6; KGF, keratinocyte growth factor; PG D2/E2/F2a, prostaglandin D2/E2/F2a; SCF, stem cell factor; SHH, sonic hedgehog; TGF, transforming growth factor; TNF- α , tumor necrosis factor α ; VDR = vitamin D receptor; WNT, wingless-type integration site.

To date, there is no permanent cure for AGA, which often precipitates anxiety and depression in affected patients [ 14 ]. Two drugs, topical minoxidil and oral finasteride, have been approved by the United States Food and Drug Administration for AGA, with finasteride restricted to men because of teratogenicity in women of child-bearing age and poor effects in postmenopausal women. While their mechanism of action is not fully understood, minoxidil is believed to shorten the telogen phase, accelerate the telogen-exogen phase, initiate premature entry of resting hair follicles into the anagen phase, and increase hair follicle size [ 15 ]; in contrast, finasteride is a type II 5- α reductase that inhibits the final conversion step of testosterone to its active form, DHT [ 16 ]. Both drugs can curtail progressive hair loss and stimulate new hair growth. However, their efficacy is suboptimal. Studies have shown that, after 1 year and 4 months of administering oral finasteride and 5% topical minoxidil, respectively, only 48% and 38.6% of the subjects, respectively, experienced hair growth [ 17 , 18 ]. Additionally, a study revealed that finasteride was ineffective in treating hair loss in postmenopausal women [ 19 ]. Furthermore, finasteride is contraindicated in women of childbearing age because of teratogenicity concerns (Propecia (U.S. package insert) 2013 Merck: Whitehouse Station, NJ), while some men would experience sexual dysfunction from its use. Scalp irritation may occur due to topical minoxidil, which, in addition to instances of suboptimal efficacy, has been cited by some patients as a reason for seeking botanical alternatives to pharmaceuticals [ 20 , 21 ]. Therefore, there is an unsatisfied need for additional safe and effective therapies for AGA.

Another cause of hair loss is traction alopecia (TA), which results from continuous and prolonged tension to the hair. It is most commonly observed in Black/African American women and children who wear hairstyles that pull excessively at the frontotemporal hairline [ 22 ]. TA typically affects the frontal and temporal scalp, as well as anterior and superior to the ears. Hairstyles reported by patients with TA include tight braids, weaves, cornrows, ponytails, chignons, or religious head coverings. It should be noted that traction applied to chemically treated hair (i.e., relaxers and dyes) can further increase the risk of TA [ 23 ]. The finding of retained hairs along the frontal and/or temporal hairline (“fringe sign”) can help in making a clinical diagnosis of TA [ 24 ]. Apart from avoiding all the practices that lead to TA, treatment options have included intralesional corticosteroids directed at the periphery of hair loss to suppress perifollicular inflammation [ 25 ], antibiotics used early in the disease for their anti-inflammatory effect [ 26 ], minoxidil [ 27 ], and hair transplantation.

Central centrifugal cicatricial alopecia (CCCA) is another common cause of alopecia in African American women, perhaps only exceeded in frequency of hair loss by TA, with a likely prevalence of 3–7%, although its true prevalence in various populations is unknown [ 28 ]. A genetic basis involving mutations in PAD13 , which encodes a protein that is essential for proper hair-shaft formation, has been associated with CCCA [ 29 ]. Harsh hair grooming practices may precipitate CCCA in genetically predisposed individuals. The scarring alopecia that results from CCCA occurs mainly on the vertex of the scalp with symmetric spread in a centrifugal pattern, hence the name of the disease. The presence of a peripilar white halo as a feature found under dermoscopy, along with other findings, suggests CCCA in an African American patient with mild central thinning. Medical treatments similar to those used for TA have been used, as well as hydroxychloroquine and doxycycline, although all are inadequate and mostly ineffective.

Lastly, there is diffused thinning in postmenopausal women, likely due to the decline in estrogen, which protects hair in women, which would have succumbed to hair loss from androgenic pattern hair loss [ 30 ]. Men manifest hair loss from androgenic alopecia early in life because they lack estrogen which protects women from the same problem. However, during and after menopause, the protective effect of estrogen is lost. This accounts for the onset of hair loss, which typically manifests as diffuse hair thinning. Estrogen supplementation is generally not an option because of the inherent dangers of increased risk of breast cancer, as well as other complications of estrogen treatment. As a result, minoxidil is used but is often not effective.

Botanical extracts are obtained from whole plants or specific plant parts, such as the flower, stem, leaves, bark, root, or fruit, and are delivered topically or as dietary supplements. Extracts are typically complex mixtures consisting of numerous individual phytochemical constituents and potential contaminants. Their use as therapeutics has expanded enormously in the last few decades. This approach is attractive, as its wide availability and low cost will allow many different formulations to be devised to address specific disease-related problems. However, a few botanicals are subject to regulation or rigorous research, as they are not labeled for a specific disease [ 31 ]. Consequently, their effectiveness or safety is often unclear.

We report the treatment outcomes of five patients treated with a new topical lotion consisting of over 12 phytoactive botanical ingredients and discuss the possible mechanisms of action using published literature.

2. Case Presentation

2.1. evaluation of dr. ugro gashee® efficacy and safety.

The study was conducted in accordance with the Declaration of Helsinki (1964). All patients signed informed consent forms.

A diverse group of five patients (in terms of age, sex, race, and cause of hair loss) who exclusively used Dr. UGro Gashee ® (GASHEE) for their hair treatment is reported. They all reported a high satisfaction level and safety profile after using the topical cosmeceutical.

2.2. Case 1

A 68-year-old Caucasian woman had AGA with significant hairline recession and thinning of the front, top, and crown. She desired to stop her hair loss, as well as stimulate hair growth in the affected areas, and therefore began applying 2% topical minoxidil solution to the affected area as well as taking oral hair- and nail-growth supplements. After over 1 year of using minoxidil without noticeable results, she discontinued both treatments (Figures 2(a) and 3(a) ). She began applying the GASHEE lotion formulation to her scalp once at night for 3 months. After leaving the lotion on her scalp throughout the night, she washed her scalp each morning. In between washings, she noted a reduction in the rate of hair shedding. After 3 months, new hair growth in the affected area was observable, and her hair loss completely stopped (Figures 2(b) and 3(b) ). Trichograms (Dino-Lite 1.3MP, AnMo Electronics Co., New Taipei City) of a tattooed spot in the hair path line area of the midscale, performed at 2, 3, and 15 months, revealed progressive interval improvement in hair density and caliber (Figures 4(a) – 4(c) ). She reported no adverse effects.

Patient 1: a 68-year-old Caucasian woman. Top of the head before (a) and after (b) 3 months of treatment.

Patient 1: back of the head before (a) and after (b) 3 months of treatment.

Trichograms of a tattooed spot in the hair path line area of the midscale from patient 1, performed at 2, 3, and 15 months ((a), (b), and (c), respectively). A progressive interval improvement in hair density and caliber was noted.

2.3. Case 2

A 48-year-old, premenopausal, Chinese woman with hair loss caused by female-pattern hair loss ( Figure 5(a) ) had a family history of advanced female- and male-pattern hair loss, specifically in her mother and brother. She washed her hair three to five times a week and typically kept her hairstyle natural. She did not want to use pharmaceuticals or any oral treatments and began applying GASHEE lotion to her hair and scalp every night. After 3 months of using the product, she reported hair growth in the areas where the spray lotion was applied to her scalp ( Figure 5(b) ), and no adverse effects were reported.

Patient 2: a 48-year-old Chinese woman. Top of the head before (a) and after 3 months of treatment (b).

2.4. Case 3

A 35-year-old African American male patient with hair loss used minoxidil and finasteride for 12 years with minimal benefits ( Figure 6(a) ). He applied GASHEE lotion to his hair and entire scalp twice a day. After 4 months of using the product, he reported decreased scarring and inflammation of his scalp and increased hair density in areas where he applied the lotion formulation (Figures 6(b) ). He reported no adverse effects.

Patient 3: a 35-year-old African American man. Crown before (a) and after 3 months of treatment (b).

2.5. Case 4

A 50-year-old African American woman had a history of hair loss in her hairline, temple edges, and the nape area, all consistent with a clinical diagnosis of traction alopecia (Figures 7(a) and 8(a) ). Similarly, she had a biopsy-proven diagnosis of central centrifugal cicatricial alopecia involving the vertex ( Figure 9(a) ). She had used topical minoxidil for over 1 year on all areas of hair loss, as well as intralesional steroid injections, albeit with minimal benefits. After discontinuing all treatments, she began applying the GASHEE lotion twice a day. At 3 months, she reported significant improvement of hair fullness in the hairline, temples, and her nape areas of traction alopecia (Figures 7(b) and 8(b) ). She equally observed some improvements in the vertex, with the exception of shiny scarred areas which were devoid of hair follicles ( Figure 9(b) ). She reported no adverse effects.

Patient 4: a 50-year-old African American woman diagnosed with central centrifugal cicatricial alopecia in the vertex and midscalp and traction alopecia in the temple, hairline, and nape areas. Right temple before (a) and after (b) 3 months of lotion use.

Patient 4: back of the head before (a) and after (b) 3 months of lotion use.

Patient 4: top of the head before (a) and after (b) 3 months of lotion use.

2.6. Case 5

A 56-year-old, postmenopausal, Hispanic woman completed chemotherapy for breast cancer and developed hair loss. When it regrew, she had generalized thinness with marked appearance in the crown, top, and frontal areas. She similarly reported a global loss of volume and inability to grow her hair long. Treatment with minoxidil for over 1 year showed no improvement. Within 6 weeks of initiating GASHEE lotion application, she noticed improvement in her global hair volume. Improvement was sustained through 18 months of documentation. She reported no adverse effects. Figures 10(a) and 10(b) depict the crown before and after 9 months of treatment.

Patient 5: a 56-year-old, postmenopausal, Hispanic woman with marked thinning in the crown area, global loss of volume, and inability to grow hair long. Crown and back of head before (a) and after (b) 9 months of treatment.

3. Discussion

3.1. dr. ugro gashee®.

Dr. UGro Gashee® (FineTouch Laboratories: Manhattan Beach, CA) is a novel, proprietary topical formulation consisting of over 12 different botanicals, vitamins, and cosmeceuticals, available as a liquid lotion or pomade, containing a similar amount of phytoactives. Each of its components has been incorporated to potentially apply a multifaceted approach to the treatment of AGA ( Table 1 ). Similarly, the formulation contains methylsulfomethane, designed to aid penetration of the active topical ingredients [ 32 ]. Since it is used as a topical formulation, it minimizes adverse or toxic effects that are sometimes experienced after the ingestion of botanical extracts. The ingredients are derived by either cold pressing or using natural solvents, thus keeping in alignment with a holistic approach to cosmeceuticals and health care. In addition, the preparation of many topical botanical solutions involves the use of high temperatures to attain a desired texture or achieve maximum dissolution and emulsification. However, such an approach may destabilize or deactivate heat-sensitive phytochemicals, thus defeating the purpose of their use. Using ingredients obtained by implementing methods based on close-to-ambient temperatures and a formulation process that avoids heat, the biochemical or biological activity of active components is optimally retained.

Components of Dr. UGro Gashee®.

DHT: 5-dihydrotestosterone; DKK-1: Dickkopf WNT signaling pathway inhibitor 1; EGCG: epigallocatechin gallate; IGF-1: insulin growth factor 1; INCI: International Nomenclature of Cosmetic Ingredients; ROS: reactive oxygen species; TGF: transforming growth factor.

Furthermore, GASHEE formulation favors using whole extracts as opposed to compounds isolated from plants. There is evidence suggesting that, at comparable doses and concentrations, industrially isolated compounds do not have as much activity as the unrefined plant due to the absence of interacting substances present in the extract [ 52 ].

Finally, one issue that has made many topical botanicals commercially nonviable is the inability to preserve them such that their shelf life is optimal without resorting to harsh chemical preservatives. GASHEE overcomes this challenge owing to its heat-free proprietary formulation process and blend of ingredients, as well as the naturally derived sustainable preservatives it contains. All of these factors are aimed at the increasing number of people who are reluctant to consume pharmaceuticals and oral medications and prefer topical natural solutions that are safer.

3.2. Dr. UGro Gashee® Ingredients and the Hair Follicle Cycle

Human hair follicles are in a constant state of cycling throughout their biological life. The cycle ( Figure 1 ) consists of a growth phase (anagen) during which the follicle elongates and is at its thickest in caliber; a degeneration phase (catagen) which marks the end of anagen and is characterized by apoptotic changes involving the sections that extend from and include the hair bulb where DPCs reside to the bulge area where the hair stem cells live; and a resting phase (telogen) during which follicle miniaturizes and may shed (exogen). Resumption of anagen is marked by regeneration of the hair bulb and the hair follicle sections leading up to the follicle bulge area.

Several genes encode proteins that act as activators or inhibitors in the three stages of the hair follicle cycle ( Figure 1 ). Understanding the mechanism underlying the influence of various components of the GASHEE formulation on many of these proteins will elucidate how it can be of benefit against hair loss. For example, one of the primary active constituents of green tea, epigallocatechin, is a DHT inhibitor, which prevents insulin-like growth factor- (IGF-) 1 levels from being depressed. IGF-1 prevents hair follicles from transitioning from anagen to catagen while encouraging the telogen to anagen transition [ 47 ]. Eclipta alba extract includes substances that can downregulate TGF-1 β , a cytokine that encourages the hair follicle to transfer to the catagen phase, although the exact regulation pathway by which this occurs remains unknown [ 50 ]. Fenugreek extract can counteract the effects of proinflammatory cytokines, such as IL-6 and tumor necrosis factor- (TNF-) α , thus positively intervening in anagen-to-catagen and catagen-to-telogen stages of the hair cycle [ 53 ]. An abnormally functioning vitamin D receptor and inadequate vitamin D3 levels are known to disrupt the normal hair follicle cycle [ 51 , 54 ]. Extracts of Gotu kola have been shown to be angiogenic. The angiogenesis marker, vascular endothelial growth factor, can mitigate androgen-induced apoptosis through the phosphoinositide-3-kinase-protein kinase B (Akt) pathway, which could affect the progression of anagen to catagen [ 55 , 56 ].

3.3. Main Dr. UGro Gashee® Ingredients in Detail

3.3.1. gotu kola.

Gotu kola ( Centella asiatica ( C. asiatica )) is an herb used for thousands of years in the Ayurvedic Indian tradition, the activities of which have been attributed to several saponin moieties [ 57 , 58 ]. Extracts of this herb have demonstrated antioxidant activity, as evidenced by several murine studies. For example, administration of Gotu extracts resulted in a significant oxidative defense in an Alzheimer's disease model [ 59 ]. In a neuroprotective model, C. asiatica mitigated the neurotoxic effects of 3-nitropropionic acid on oxidative stress in the cytosol and mitochondria and prevented the significant depletion of glutathione, total thiols, and other enzymic antioxidant systems [ 59 , 60 ]. Finally, a significant decrease in malondialdehyde and an increase in glutathione and catalase levels were observed in male Wistar rats treated with 200 and 300 mg/kg of C. asiatica [ 33 ]. Notably, C. asiatica extracts were demonstrated to activate the hair-inductive capacity in cultured human DPCs [ 61 ].

3.3.2. Green Tea Extract

Green tea extract is made from leaves of the plant, Camellia sinensis L. (Theaceae), in which enzymatic oxidation has been minimized. It is one of the most extensively studied botanicals due to its antioxidant, metal-chelating, anticarcinogenic, anti- and proapoptotic, and anti-inflammatory properties, originating from constituent catechins, 50–80% of which consist of epigallocatechin gallate (EGCG) [ 62 ]. An early study used BALB/black mice devoid of hair on the head, neck, and dorsal areas and randomly assigned them to an experimental group treated with 50% fraction of polyphenol extract from dehydrated green tea in their drinking water for six months and a control group given plain water. The authors showed that one-third of the mice in the experimental group had significant hair regrowth ( p =0.014) compared to that in the control group [ 63 ]. Similarly, further investigation revealed that EGCG promotes hair growth in an ex vivo culture of hair follicles and the proliferation of cultured DPCs [ 64 ]. The authors suggested that growth stimulation of DPCs by EGCG in vitro was mediated by the upregulation of phosphorylated extracellular signal-regulated kinases and Akt, which are important for regulating cell growth, proliferation, survival, mobility, and invasion, as well as by the increased B-cell lymphoma 2/bcl-2-like protein 4 ratio, functioning like a rheostat to determine cell susceptibility to apoptosis. Notably, similar results were also obtained in vivo in dermal papillae of human scalps [ 64 ].

Finally, researchers used a micro-RNA (miRNA) microarray to identify miRNA expression levels in DPCs and determine the influence of this expression on the protective effects of EGCG against DHT-induced cell death, growth arrest, intracellular reactive oxygen species (ROS) levels, and senescence [ 65 ]. The experiments demonstrated that EGCG does protect against the effects of DHT by altering the miRNA expression profile in human DPCs, attenuating DHT-mediated cell death and growth arrest and decreasing intracellular ROS levels and senescence.

3.3.3. Fenugreek

Fenugreek ( Trigonella foenum-graecum ) is a traditional medicinal herb commonly used in India, China, Thailand, and South-East Asian countries [ 66 ]. Bioactive molecules identified in extracts include saponins, flavonoids, coumarins, and alkaloids, targeting several molecules involved in inflammation and cancer cell proliferation, invasion, migration, angiogenesis, and metastasis [ 66 , 67 ].

The antioxidative and anti-inflammatory properties of fenugreek have been noted in several studies [ 68 – 73 ]. It demonstrated a significant acute anti-inflammatory activity relative to water (control) and sodium diclofenac (standard) in mice with carrageenan-induced rat paw edema [ 68 ]. Diosgenin, the major steroidal sapogenin in the fenugreek seed, has demonstrated various anti-inflammatory functions, such as reducing the production of several inflammatory mediators, including nitric oxidase, IL-1, and IL-6, in murine macrophages [ 69 , 70 ]. Similarly, it has been shown to inhibit superoxide generation in bone marrow-activated mouse neutrophils along with blocking cyclic adenosine monophosphate, protein kinase A, cytosolic phospholipase A2, p21-activated kinase, Akt, and mitogen-activated protein kinase (MAPK) signaling pathways [ 71 ]. This eventually leads to a reduction in the adhesive capacity of vascular smooth muscle cells (VSMCs) and TNF- α -mediated induction of intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 in VSMCs by inhibiting the MAPK/Akt/nuclear factor- κ B signaling pathway and ROS production [ 72 ]. Additionally, it has been demonstrated to alleviate oxidative stress and inflammatory and apoptotic markers induced by monocrotaline [ 73 ].

In conclusion, the results reported here in five patients with hair loss show that meaningful improvement with a high safety profile was attainable using a topical botanical formulation that focuses on multiple targets of pathophysiologic hair-loss pathways. This formulation may present an alternative for people who wish to avoid the use of pharmaceuticals either due to concerns of adverse effects or suboptimal efficacy. A large randomized, double-blind, placebo-controlled study would be necessary to define the safety and efficacy of this formulation.

Data Availability

Conflicts of interest.

Dr. Sanusi Umar has ownership shares in FineTouch Laboratories, Inc., which owns Dr. UGro Gashee®. Dr Marissa J. Carter has no conflicts of interest.