Androgenetic alopecia (AGA), also known as seborrheic alopecia or male pattern baldness, is the most prevalent form of alopecia. The incidence of AGA increases with age, and it is most commonly observed in White people. The incidence of AGA was found to be 50% among White men and 19% among White women,(p1) followed by Asians (21.3% in men and 6.0% in women),(p2) African Americans, and Native Americans.(p3) Regardless of age or stage of baldness, AGA can lead to lower self-esteem, diminished confidence, and distress in affected individuals.(p4) AGA exhibits variations in terms of the age of onset, location on the scalp, and severity levels among individuals.(p5) Histologically, AGA is characterized by several features, including follicular miniaturization, perifollicular inflammation, fibrosis in the pilosebaceous unit, angiofibrotic tracts, follicular stelae, and signs of follicle destruction or hair shaft damage.(p6) In men, AGA typically occurs in the temporal and vertex regions while sparing the occipital region, resulting in a characteristic ‘horseshoe’ pattern.(p5) Women with AGA commonly experience diffuse hair thinning over the central scalp, while the frontal hairline remains intact.(p7)

AGA is a polygenic disease, and its exact pathogenesis is not fully understood. The risk genes associated with it are yet to be fully identified.(p8) The primary causative factor of AGA is the male hormone testosterone, which is potent and the main androgen in males. Testosterone undergoes conversion by 5α-reductase enzymes (5αR I and 5αR II) into the more potent dihydrotestosterone (DHT), which binds more strongly to the androgen receptor (AR).(p9) The action of DHT on hair follicles (HFs) leads to a shortening of the anagen (growth) phase and a reduction in HF size.(p10) This is accompanied by an increased telogen (resting) phase and degeneration of HF.(p8) Consequently, the HF becomes shortened, preventing hair from penetrating the epidermis and eventually leading to alopecia.

AGA is impacted by a multitude of factors. Both innate and acquired factors regulate its pathogenesis. Innate factors include the higher sensitivity of HFs to DHT and elevated levels of androgens or 5α-reductase, resulting in an elevated level of DHT in the scalp and increased susceptibility to alopecia. Acquired factors are commonly related to lifestyle choices, including dietary habits, occupational factors, and quality of rest. Individuals experiencing high levels of stress may have continuous nervous tension, leading to excessive hormone secretion, endocrine disorders, and an increased risk of alopecia.(p11) Additionally, excessive secretion of scalp oil in some individuals promotes the growth of microorganisms, causing seborrheic dermatitis and adversely affecting the scalp microenvironment, which can impact the health of HFs.(p12) Moreover, as individuals age, changes in androgen metabolism and increased activation of ARs result in elevated production of DHT in HF and prolonged effects on the receptors, thus contributing to the development of AGA.(p13)

In light of the established pathogenesis of AGA, the current treatment approach revolves around targeting one of the pathways involving testosterone synthesis, reduction of testosterone to DHT, or binding of DHT to the AR.(p6) Due to testosterone’s crucial involvement in physical development and physiological function, it is clearly unfeasible to combat AGA by suppressing testosterone production.(p14)

Currently, the most frequently prescribed medications for the treatment of AGA in clinical practice are minoxidil and finasteride (Figure 1). (p15)

Originally developed as an oral medication for hypertension, minoxidil functions as a potassium channel-opening agent.(p16) Interestingly, as a side effect, increased body hair growth (including hair on the scalp) has been observed during its usage.(p17) However, it is important to note that although topical minoxidil has shown efficacy in promoting hair growth, some patients may experience irritant contact dermatitis, which can result in adverse reactions such as pruritus, so scaling is important.(p18) During the initial stage of usage, transient alopecia can occur, which can negatively impact long-term compliance and treatment effectiveness.(p19) The mechanism behind the effects of minoxidil on hair growth is not fully understood.

Finasteride is a selective inhibitor of 5αR II.(p20) This medication has been found to enhance hair regrowth and increase hair count.(p21) However, finasteride can also cause adverse effects such as sexual dysfunction and depression.(p22) Another limitation of finasteride is its unsuitability for women. Studies have shown that finasteride is ineffective in treating alopecia in postmenopausal women, possibly due to their lower androgen levels.(p23) Additionally, finasteride is contraindicated for women of childbearing age due to its teratogenic potential.(p24) Moreover, it has been observed that the use of finasteride is associated with an increased risk of prostate cancer malignancy.(p25) Therefore, it is necessary to identify novel therapeutic targets for treating AGA and explore the efficacy of drugs targeting these specific objectives.

Recently, thyroid receptor β (TRβ) has been demonstrated to hold significant potential as a novel target for alopecia treatment. A series of animal experiments have also shown the effective role of TRβ agonists in combating AGA. This provides a promising avenue for the development of future alopecia medications. This review focuses on TRβ as a therapeutic target for alopecia and elucidates its mechanism of action in preventing AGA. Minoxidil stimulates hair growth by activating potassium ion channels, whereas finasteride exerts its anti-hairloss effects by inhibiting 5αR II. However, neither drug directly impacts the hair cycle, a crucial factor influencing hair growth. In contrast to minoxidil and finasteride, TRβ agonists can directly modulate the hair cycle through diverse pathways, playing a more significant role in promoting healthy hair growth. Additionally, with careful consideration of the selectivity for TR subtypes and precise dosage control, TRβ agonists may avoid the serious side effects often associated with minoxidil and finasteride. We provide an overview of the existing TRβ agonists for AGA treatment and introduce candidate compounds with potential anti-AGA effects. We also summarize and analyze their structure–activity relationships (SARs), providing a foundation for further development of TRβ agonists with potent anti-AGA efficacy.