記住我
REVIEW ARTICLE
Year : 2023 | Volume
: 41
| Issue : 2 | Page : 78-86
Current understanding and treatment of sex hormone-related hair diseases
Tyng-Shiuan Hsieh1, Ling-Ying Tsai2, Ming-Ying Wu3, Sung-Jan Lin4
1 Department of Dermatology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
2 School of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
3 Department of Dermatology, Chang Gung Memorial Hospital, Linkou Branch; School of Medicine, College of Medicine, Chang Gung University, Taoyuan; Graduate Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan
4 Department of Dermatology, National Taiwan University Hospital and College of Medicine; Department of Biomedical Engineering, National Taiwan University; Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan
Correspondence Address:
Dr. Ming-Ying Wu
Department of Dermatology, Chang Gung Memorial Hospital, Linkou Branch, No. 5, Fuxing St., Guishan Dist., Taoyuan 333
Taiwan
Prof. Sung-Jan Lin
Department of Biomedical Engineering, National Taiwan University, No. 1, Sec. 1, Jen-Ai Rd., Taipei 100
Taiwan
Source of Support: None, Conflict of Interest: None
DOI: 10.4103/ds.DS-D-22-00162
Hair follicle (HF) growth is regulated by local and systemic environments. Sex hormones, a systemic factor, paradoxically promote and suppress hair growth in different sites of the body, leading to diseases such as hirsutism, androgenetic alopecia, and female pattern hair loss. The past decades have seen progress in the treatment of sex hormone-related hair diseases, but the pathogenesis of some of these diseases remains obscure and even controversial. We review the biological effects of major sex hormones on hair growth and summarize their known impacts. We discuss the different responses of animal and human HFs to sex hormones, summarize the pathogenesis of sex hormone-related hair diseases, and highlight the benefits of and controversies in the current management of these diseases. Finally, we discuss future research directions such as interactions between sex hormones and the immune system and the possible role of epigenetics in these hair disorders.
Keywords: Androgenetic alopecia, female pattern hair loss, hair follicles, hirsutism, sex hormones
Human hair has versatile functions, including physical protection, thermoregulation, sensation, and social communication.[1] Loss or even overabundance of hair has a negative impact on self-image and sense of well-being and can induce psychosocial distress in affected individuals.[2] The hair shaft is the product of the hair follicle (HF), a cylindrical mini-organ composed of epithelium and mesenchyme[1][Figure 1]. Hair growth occurs in cycles consisting of three phases: anagen (growth), catagen (regression), and telogen (rest). Anagen, the phase of hair growth when hair shafts are actively produced, is marked by rapid cell division and differentiation in the hair bulb and is estimated to last for 2–6 years or even longer in scalp HFs.[3] Catagen, a short transitional phase that usually lasts about 2–3 weeks in scalp HFs; the lower segment of the HF regresses through a sophisticatedly controlled apoptotic process.[3] Telogen is a stage of relatively low cell proliferative activity, with the proximal end of the hair shaft exhibiting a club-shaped morphology.[3]
Figure 1: HF structure and hair cycle. The HF consists of the epithelium and mesenchyme (dermal papilla). HFs undergo a growth cycle with catagen, telogen, and anagen phases. HF: Hair follicle.HF stem cells, residing in the bulge and secondary hair germ in telogen, are essential for HF regeneration.[1] Signals from the HF dermal papilla not only activate HF stem cells to power telogen-to-anagen regeneration but also guide HF regression from anagen to telogen.[1] In anagen, the dermal papilla also instructs the ordered differentiation of hair matrix cells for continuous elongation of the hair shaft.[4] The size of the dermal papilla dictates the thickness of the hair shaft produced.[1] The proper functioning of HFs relies on HFs themselves as well as on extrafollicular regulation by local and systemic environments.[5] Previous work has unraveled the importance of the hormonal effect on hair growth.[6] In this review, we mainly focus on the effects of sex hormones on hair growth and briefly summarize other hormones that have also been reported to influence hair growth [Table 1].
Table 1: The central and local effects of hormones involved in the hair follicle regulation (summarized from Inui and Itami[7])Steroid hormones are mainly produced in adrenal or gonadal cells. Steroidogenesis begins with the conversion of cholesterol [Figure 2]. Steroidogenic acute regulatory protein 1 facilitates the transfer of cholesterol to the inner mitochondrial membrane in a rate-limiting step. Following this, the cholesterol side-chain cleavage enzyme, P450, converts cholesterol into pregnenolone. Pregnenolone is then metabolized by 3-β-hydroxysteroid dehydrogenase to progesterone. Progesterone undergoes a two-step conversion by 17α-hydroxylase and 17, 20-lyase to androstenedione. Testosterone is produced under the action of Type III 17β-hydroxysteroid dehydrogenase. It can be further converted into dihydrotestosterone (DHT) by 5α-reductase. Aromatase is essential for the generation of estrogen.[8] Estrone (E1) and estradiol (E2) are produced from androstenedione and testosterone, respectively, by the enzyme aromatase. Estrone and estradiol can be converted to estriol (E3) in the placenta and liver.
Figure 2: The steroidogenesis process. Steroidogenesis begins with cholesterol transformation. After the delivery of cholesterol into the inner mitochondrial membrane, the P450scc converts cholesterol to pregnenolone. Pregnenolone is then metabolized by 3 β-HSD Δ 5-Δ4-isomerase to progesterone. Under 17α-OH-lase and C17-20-lyase enzyme activity, progesterone is then converted to androstenedione. Testosterone is produced through 17 HSD3 and then further converted to DHT by 5α-reductase or to estradiol by aromatase. 3 β-HSD: 3 β-hydroxysteroid dehydrogenase, 17α-OH-lase: 17α-hydroxylase, P450scc: side-chain cleavage enzyme P450, 17 HSD3: 17β-hydroxysteroid dehydrogenase Type III. Overview of Major Sex Steroid Hormones Androgens
Androgens include testosterone, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEA-S), androstenedione, and DHT. Testosterone is mainly produced in the testes, adrenal glands, and ovaries. Androstenedione originates from both the adrenal glands and the ovaries, while DHEA and DHEA-S are produced mainly in the adrenal glands. Testosterone is converted to DHT by 5α-reductase at various sites, including the prostate, skin, and HFs.[9]
Estrogen
The group of natural estrogens consists of E1, E2, E3, and their derivatives. E2 is regarded as the most potent of the three and is the major estrogen during reproductive years, while E1 predominates after menopause and E3 during pregnancy. Estrogen is produced in the adrenal glands, corpus luteum, and testes and through peripheral aromatization of androstenedione and testosterone.[10]
Progesterone
Progesterone is produced in the corpus luteum of the ovaries, adrenal glands, and placenta. Progesterone produced in the gonads is mainly released into the blood to perform its functions. On the other hand, progesterone from the adrenal glands is converted chiefly into glucocorticoids and androgens in the zona fasciculata and zona reticularis.[10]
Position-Dependent Response to Androgen/Estrogen and the Androgen ParadoxAfter puberty, elevated androgen levels promote the transformation of vellus HFs, which produce small light-colored hairs, into terminal HFs that form thicker pigmented hairs in specific body sites such as the face, pubic area, and axillae.[11] However, higher androgen levels can cause the opposite effect on the scalp, resulting in miniaturization and development of androgenetic alopecia (AGA). Three factors may be responsible for this androgen paradox: steroidogenic enzymes, androgen receptors (ARs), and AR coactivators.
Since HFs maintain their original characteristics after transplantation into other body regions, the variation in their responses to androgen is not determined by the surrounding environment, but by hard-wired intrafollicular factors. Steroidogenic enzymes, ARs, and AR coactivators all participate in the regulation of androgen sensitivity in the dermal papillae.[12] Insulin-like growth factor 1 serves as a positive mediator, while transforming growth factor-beta 1 (TGF-β1), dickkopf1, and Interleukin-6 are harmful mediators.[7] Androgen downregulates Wnt signaling, while simultaneously upregulating TGF-β signaling in balding dermal papilla cells.[13] In addition, 5α-reductase in dermal papilla cells converts testosterone to highly potent DHT, which binds to ARs and strongly enhances the transcription of TGF-β1, the catagen inducer.[14] Higher levels of 5α-reductases in the frontal region and increased sensitivity to androgens may explain the characteristic distribution of pattern hair loss.[15] Recent studies have also shown an increased expression of steroidogenic acute regulatory protein 1 in the frontal scalp, which is correlated with the elevated levels of estrogen and testosterone in tissue.[16]
The increased prevalence of hair loss following menopause suggests that estrogen deficiency or other hormonal changes associated with menopause may impair hair growth.[17] The role of estrogen in hair growth is complex and even controversial. Topical E2 arrests murine pelage HFs in telogen through estrogen receptor-α, which prematurely induces catagen development.[18] In contrast, estrogen receptor-β, the predominant estrogen receptor isoform in the human scalp, works as a silencer of estrogen receptor-α action in HFs.[19] Therefore, estrogen seems to promote hair growth on the human scalp in contrast to its action in mice. Another action of E2 on HFs is the inhibition of aromatase activity[7][Table 2]. Progesterone acts both systemically and locally on HFs. It inhibits luteinizing hormone and thus decreases theca cell stimulation and inhibits androgen synthesis.[7] In scalp skin, progesterone receptors are present in dermal papilla cells where progesterone inhibits 5α-reductase activity.[7]
Sex Hormone Production and Conversion in Hair FolliclesOver 70% of the cholesterol in the body is synthesized de novo. Similar to other organs and tissue, HF may also produce cholesterol through intrafollicular synthesis, which mainly takes place in the endoplasmic reticulum. Acetyl-CoA undergoes a series of steps to turn into cholesterol. During the process, 3-hydroxy-3-methylglutaryl-CoA reductase acts as a catalyst in a rate-limiting step, and the enzyme, 24-dehydrocholesterol reductase (DHCR24), converts desmosterol to cholesterol in the final step. DHCR24 is emphasized here owing to its high expression in HFs.[17] The current understanding of carrier-mediated cellular uptake is limited. However, evidence suggests that low-density lipoprotein receptors and the cholesterol transporter, ATP Binding Cassette Subfamily A Member 5 (ABCA5), may play crucial roles in regulating steroidogenesis in HFs.[19] Androgens also undergo peripheral conversion into a more potent form in HFs. For example, testosterone can be converted to DHT through Type I 5α-reductase in the sebaceous glands and through Type II 5α-reductase in dermal papilla cells.[20] However, the production of sex hormones through steroidogenesis in the skin is much lower than that in gonads and adrenal glands. A study of prepubertal castrated males lacking vellus-to-terminal transformation in secondary sexual hair regions suggests that de novo synthesis of sex hormones from cholesterol precursors is not sufficient to replace the loss of circulatory testosterone.[21]
Androgenetic AlopeciaClinical features and pathogenesis
As an androgen-dependent disease, AGA can develop soon after puberty. Earlier onset of AGA often results in significant psychological distress. Due to the variation in severity and age of onset, precise determination of the prevalence of AGA is challenging. It has been estimated to affect around 50% of Caucasian by the age of 50 years, with incidence increasing steadily with advancing age.[22] AGA is less prevalent in Asian populations at all ages than in European populations; however, it affects more than half of men during their lifetime.[22]
DHT, converted from testosterone, can elicit opposite responses in HFs from different body regions; for example, scalp HFs versus beard HFs.[11] This is a critical factor in HF miniaturization, evidenced by the increased levels of DHT in the balding scalp compared to the nonbalding scalp.[23] In the scalp, Type I 5-α reductase is universally present in all sebaceous glands, while Type II 5-α reductase is expressed in the infundibulum and root sheath of the HF.[22] In both men and women, the HFs harvested from the frontal scalp have a higher level of reductase compared to HFs from occipital biopsies.[15] Suppression of Type II 5α-reductase is highly effective against AGA and is now the primary treatment strategy.[22] In addition to 5α-reductase, the higher levels of ARs discovered in cultured dermal papilla cells from the balding scalp support the hypothesis that androgens, especially DHT, alter mesenchyme–epithelial interactions and compromise hair growth.[24]
Comparison of AGA in monozygotic and dizygotic male twins shows strong AGA heritability at 0.81;[25] however, the exact genetic basis for AGA remains unclear. AR gene polymorphism is shown to be associated with AGA. Three polymorphisms of the AR gene have been reported, including the StuI restriction-site polymorphism, CAG polymorphism, and GGC polymorphism. However, in a recent meta-analysis, only the StuI polymorphism was found to have a significant association, while no association was observed between the CAG or GGC polymorphisms.[26] The StuI restriction site polymorphism was found in 92.3% of male AGA patients compared to 76.6% of male controls.[27] However, the AR gene polymorphism itself is insufficient to induce AGA. Because the AR gene is located on the X chromosome, the AR gene polymorphism cannot explain the father-to-son inheritance commonly seen in AGA. A genome-wide association study identified several other susceptibility loci for AGA, i.e. 1p36.22, 2q37.3, 7p21.1, 7q11.22, 17q21.31, 18q21.1, 2q35, 3q25.1, 5q33.3, and 12p12.1.[27] In addition, nongenetic factors, including environmental factors, systemic effects, and local skin conditions, may also contribute to the development of AGA.[22]
Treatment
Minoxidil
Minoxidil, a piperidine-pyrimidine derivative, was initially developed as a potent vasodilator to facilitate the opening of ATP-sensitive potassium channels.[28] Its mechanism of hair growth promotion remains unclear. A proposed process is that minoxidil directly promotes cell proliferation by altering the cell cycle status through its effect on potassium channels.[27] In HF organ culture, minoxidil treatment prolongs anagen, while tolbutamide, an ATP-sensitive potassium channel closer, shortens it.[29] Minoxidil's primary cellular targets in the HF are the dermal papilla and dermal sheath.
Two forms of topical minoxidil are available – a liquid containing ethanol and propylene glycol to enhance the solubility of minoxidil and a propylene glycol-free topical foam. While liquid minoxidil 2% is effective against male AGA, minoxidil 5% outweighs 2% in its efficacy.[28] However, minoxidil solution containing propylene glycol has been reported to cause scalp irritation.[28] To avoid this potential side effect, a propylene glycol-free minoxidil foam formulation was later developed.[28] Low-dose oral minoxidil has been proposed as an alternative for patients who cannot tolerate the topical formulations.[30] Several side effects of oral minoxidil, including electrocardiogram abnormalities (20%), pedal edema (10%), and unwanted hypertrichosis (96%), have been reported.[29] Larger randomized studies comparing the efficacy, safety, and dose responses of oral minoxidil, with standardized measurement of hair growth, are warranted.
Finasteride and dutasteride
Finasteride, a Type II 5α-reductase inhibitor, is the first Food and Drug Administration (FDA)-approved oral medication for AGA.[31] Finasteride 1 mg/day has been shown to slow hair loss and increase hair growth in AGA patients.[30] Dutasteride inhibits both Type I and II 5α-reductase; it is three times more potent in inhibiting Type I 5α-reductase and 100 times more potent in inhibiting Type II 5α-reductase than finasteride.[31] Randomized trials revealed that dutasteride 0.5 mg/day is more efficacious than finasteride 1 mg/day at week 24 for hair loss in both the vertex and the frontal scalp. Finasteride and dutasteride have similar rates of adverse events, including erectile dysfunction, ejaculatory dysfunction, and loss of libido.[32] Topical finasteride is currently not an FDA-approved medication. However, its potential utility, alone or in combination with minoxidil, is being investigated.[33] Preliminary results showed that the effect of topical finasteride is comparable to systemic delivery and combination therapy with topical minoxidil 5% outweighs topical finasteride alone.[33]
Topical prostaglandins
Prostaglandin D2 (PGD2) production is elevated in AGA scalp. It is suggested to suppress hair growth, whereas PGE2 and PGF2α promote hair growth.[34] Cetirizine has been shown to reduce PGD2 production and inhibit local inflammatory cell infiltration.[35] Topical application of 1% cetirizine solution once per day yielded a significant improvement in AGA.[35] In a randomized double-blind placebo-controlled study, 0.1% latanoprost, a PGF2α analog that activates the PGF receptor, significantly increased terminal and vellus hair density at 24 weeks compared to the baseline and the placebo.[36]
Other treatments
Autologous hair transplantation is also recommended for patients refractory to other treatments.[31] Since AGA is a predetermined property of each HF, HFs transplanted from nonbalding regions to the balding scalp do not undergo a miniaturization process after transplantation.[37] In addition to topical and systemic medication, nonpharmacological treatments, such as photobiomodulation with light-emitting diodes or low-level laser,[31] have been demonstrated to be beneficial for AGA. A low-level laser comb was approved by the FDA for treatment of AGA.[31] The effects of photobiomodulation seem to be mediated through enhanced epithelial-mesenchymal interactions in HFs.[38] In addition, local injection with platelet-rich plasma has been shown to increase the number of hairs and improve hair thickness.[31]
Female Pattern Hair LossClinical features and pathogenesis
Female pattern hair loss (FPHL) was previously named “female AGA.”[39] Although male AGA and FPHL show a similar miniaturization process, FPHL is now a widely accepted term due to the distinct clinical presentation of the condition and the uncertain role of androgen in its pathogenesis. Most patients with FPHL do not show a significant increase in serum androgens.[40] As the most common cause of alopecia in women, FPHL affects around 55% of women in their 70s, with a higher prevalence among Caucasian women than among Korean and Chinese women.[39] Compared to patients with AGA, those with FPHL suffer from more serious impacts on their quality of life, self-esteem, and even psychosocial activity.[41]
FPHL is characterized by diffuse thinning from the vertex to the frontal scalp without a receding anterior hairline even at an advanced stage. Several scales have been developed to categorize FPHL, including the Ludwig scale, the Olsen scale, and the Sinclair scale.[42] In the early stages, trichoscopy can help make the diagnosis when miniaturization of more than 20% of HFs is observed.[39] Another key feature of FPHL is the frequent presence of kenogen,[43] a phase of absent hair shafts in HFs after hair shedding, which increases in parallel with the severity FPHL. It indicates earlier hair shedding during telogen, with delayed entry into anagen.
The role of estrogen in the pathogenesis of FPHL is controversial. While postmenopausal women with decreased estrogen are the most vulnerable to FPHL,[44] earlier puberty, fewer childbirths, and longer oral contraceptive use with prolonged estrogen exposure are risk factors for FPHL.[45] An Australian study showed that three variants of the estrogen receptor-β gene (rs10137185, rs1701774, and rs2022748) are associated with FPHL.[46] However, this result is not entirely consistent with findings of studies from Germany and the United Kingdom.[46] Aromatase is the key enzyme responsible for estrogen biosynthesis. An investigation of variants of the aromatase gene (CYP19A1) in different ethnic groups (from Australia, the United Kingdom, Germany, and China) could not find a conclusive association with FPHL.[45] Women with shorter CAG and GGC repeats on the AR gene have a higher risk of developing FPHL.[47] However, another study found no association between FPHL and the AR gene, in contrast to the correlation in male patients.[48] Therefore, further studies may be warranted to confirm the role of AR in FPHL.
The microinflammation process, especially in the upper segment of the HF, has been proposed as a possible element in the pathogenesis of AGA and FPHL.[49] An inflammatory infiltrate, mainly consisting of CD4+ lymphocytes, is more evident in miniaturized HFs and is correlated with higher apoptosis.[50] FPHL is also associated with higher fasting glucose and factors related to hormones, i.e. prolonged estrogen exposure.[45] These findings indicate that local inflammation and systemic factors other than sex hormones may also contribute to the pathogenesis of FPHL.
Treatment
Minoxidil
Topical minoxidil solution is the first-line treatment for FPHL. When applied twice daily, the 5% minoxidil solution is superior to the 2% solution for improving hair count, patient self-assessment, and investigator assessment at week 48.[28] Drug-related adverse events, including pruritus, dermatitis, hypertrichosis, and scales, are more common in those treated with the 5% minoxidil solution due to its higher propylene glycol content.[28] Oral minoxidil has also been shown to be an effective treatment for FPHL. The oral minoxidil dosage ranges from 0.25 mg to 2 mg per day.[28] The side effects of oral minoxidil include sodium and fluid retention, cardiovascular effects, and hypertrichosis.[28]
Spironolactone
Spironolactone is the most commonly used off-label antiandrogen for treating FPHL and hirsutism. Spironolactone is a potassium-sparing diuretic that acts as an androgen antagonist by competitively blocking ARs in the target tissue and inhibiting adrenal androgen production.[51] The effective daily dose is 100–200 mg, but it should be titrated starting at 50 mg daily.[51] The side effects of spironolactone include postural hypotension, electrolyte disturbances, and menstrual irregularities.[52] Thus, blood pressure and electrolyte balance should be monitored during the first few months of treatment.[52]
Finasteride and dutasteride
Although finasteride is widely used to treat men with AGA, studies of finasteride use in women are relatively limited owing to the risk of teratogenicity in the male fetus.[53] Treatment of postmenopausal women with finasteride at 1 mg/day for 1 year did not significantly slow hair thinning, increase hair growth, or improve the appearance of hair compared to a placebo.[52] A medium dosage of finasteride at 2.5 mg/day in combination with oral contraceptives was efficacious in normoandrogenic women with FPHL. However, the antiandrogenic effect of the concomitant contraceptives might have contributed, possibly in part, to the clinical outcome.[53] High-dosage finasteride at 5 mg/day for 12 months resulted in pronounced clinical improvement in both premenopausal and postmenopausal women with normal androgen levels. However, patients over 70 years of age exhibited the poorest clinical response.[52] A topical formulation has been proposed to minimize the unwanted systemic side effects of finasteride, particularly in women of childbearing age, but it regrettably shows a limited efficacy.[33]
Dutasteride is a potent second-generation 5α-reductase inhibitor that blocks both Type I and II 5α-reductase isoenzymes. The case of a 46-year-old woman with FPHL, who did not respond to minoxidil and responded a little to finasteride, showed a marked improvement after 9 months of dutasteride therapy at 0.5 mg/day.[54] Further studies comparing dutasteride with finasteride and placebo are warranted to determine its safety and efficacy.
Flutamide
Flutamide is an oral antiandrogen medication first used for managing hyperandrogenetic alopecia.[31] In a single-center, open-label, randomized controlled trial of treatments for hyperandrogenic premenopausal women with FPHL, flutamide at 250 mg/day was the only agent resulting in a significant reduction in Ludwig scores compared to cyproterone acetate and finasteride.[55] Although flutamide is well known for its hepatotoxicity, a low flutamide dosage (62.5 mg/day) shows hepatic tolerability.[56] Other common side effects include hot flushes and interaction with warfarin.[31]
Other treatments
A growing number of innovative treatments have been developed to stimulate hair growth in women with FPHL. As for male patients, photobiomodulation with low-level light is an alternative or additive treatment option for women with FPHL.[57] Invasive procedures include fractional lasers and microneedling, in which laser beams or tiny needles create microtrauma in areas of hair loss. Their hair growth-promoting effects possibly depend on trauma-induced low-level inflammation, growth factor production, or neovascularization.[57] Hair transplantation can also be considered for FPHL patients. Due to the progressive nature of FPHL, a careful selection of patients and in-depth discussions with them are crucial to achieve a favorable result.
HirsutismHirsutism, the condition of excessive terminal hair in androgen-dependent areas, affects 5%–10% of women of reproductive age.[58] Hirsutism is mainly caused by hyperandrogenism, which is often attributed to ovarian or adrenal diseases (e.g. polycystic ovary syndrome [PCOS], congenital adrenal hyperplasia, and androgen-secreting tumors of the adrenal glands or ovaries), insulin resistance, obesity, or medication.[58] Intriguingly, the presentation of hirsutism reflects a complex interaction between circulating androgen levels and the sensitivity of HFs to androgens. The severity of hirsutism is not necessarily correlated with plasma androgen concentrations, and hirsutism may develop without the presence of excess androgen (idiopathic hirsutism).[58] PCOS is the most common endocrine disorder associated with hirsutism, followed by idiopathic hyperandrogenemia. PCOS typically presents from puberty and is accompanied by disturbances of the menstrual cycle, weight gain, dyslipidemia, insulin resistance, acne, and acanthosis nigricans.[59]
The modified Ferriman–Gallwey scoring system is the most widely used method of evaluating hirsutism in women.[58] The score is used to evaluate nine body parts (excluding forearms and lower legs), which are the most sensitive to androgen, on a scale of 0–4 based on visual inspection. A score of 0 indicates the complete lack of terminal hair growth, and a score of 4 represents full male-pattern terminal hair growth. A summed score of ≥8 indicates hirsutism. In terms of the severity of the condition, a summed score of >15 indicates moderate-to-severe hirsutism and 8–15 indicates mild hirsutism.[58]
Treatment for hirsutism includes hormone therapy and cosmetic measures. Oral contraceptives containing estrogen and progestins with antiandrogenic activity, such as cyproterone acetate and drospirenone, are effective and can be the first-line therapy, especially for those who need contraception and are not at risk of venous thromboembolism.[58] Antiandrogens or 5α-reductase inhibitors have also been proven to be effective, but should be used cautiously due to their teratogenic potential.[60] Other therapeutic strategies such as hair bleaching, shaving, or laser epilation can also effectively disguise or remove unwanted hair.
Questions and Future DirectionsThe role of epigenetics in sex hormone-related hair disorders
Despite extensive genetic studies of AGA and FPHL, no definite mutations specific to these diseases have been discovered. A research direction for the pathobiology of AGA and FPHL is the potential involvement of epigenetic regulation. A study from Japan of 11 monozygotic twins with AGA showed distinct differences in hair volume in five out of the 11 pairs, suggesting that factors other than the DNA genetic code are also involved.[61] HF stem cells fuel hair regeneration, and defective HF stem cell activity can lead to alopecia.[5] HF stem cell activity is also subject to epigenetic regulation among regulatory networks.[62] These findings suggest that AGA and FPHL may not be caused by a single gene mutation, but possibly by an epigenetically controlled gene expression profile in a patterned distribution, such as the patterned expression of Type II 5α-reductase in the dermal papillae in the balding region of AGA or patterned expression of sex hormone biosynthesis genes in the balding regions of FPHL. We suggest that epigenetic regulation is a promising area of research to unveil the puzzling hereditary mode and intricate pathobiology of AGA and FPHL.
Data availability statement
Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.
Financial support and sponsorship
This work is supported by Taiwan Bio-development Foundation (to SJL), Taiwan Ministry of Science and Technology (MOST110-2314-B-002-190-MY3 to SJL), and National Taiwan University Hospital (111IF0006 to SJL).
Conflicts of interest
Prof. Sung-Jan Lin, an editorial board member at Dermatologica Sinica, had no role in the peer review process of or decision to publish this article. The other authors declared no conflicts of interest in writing this paper.
References
留言 (0)