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Citation: Owecka, B.; Tomaszewska,
A.; Dobrzeniecki, K.; Owecki, M. The
Hormonal Background of Hair Loss in
Non-Scarring Alopecias. Biomedicines
2024,12, 513. https://doi.org/
10.3390/biomedicines12030513
Academic Editors: Fabio Rinaldi and
Daniela Pinto
Received: 7 February 2024
Revised: 18 February 2024
Accepted: 22 February 2024
Published: 24 February 2024
Copyright: © 2024 by the authors.
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biomedicines
Review
The Hormonal Background of Hair Loss in Non-Scarring
Alopecias
Barbara Owecka 1, Agata Tomaszewska 1, Krzysztof Dobrzeniecki 1and Maciej Owecki 2, *
1Students’ Scientific Association in Public Health, Pozna´n University of Medical Sciences (PUMS),
´
Swi˛ecickiego 6, 60-781 Pozna´n, Poland; kd34610@gmail.com (K.D.)
2Department of Public Health, Pozna´n University of Medical Sciences (PUMS), ´
Swi˛ecickiego 6,
60-781 Pozna´n, Poland
*Correspondence: mowecki@ump.edu.pl
Abstract: Hair loss is a common clinical condition connected with serious psychological distress
and reduced quality of life. Hormones play an essential role in the regulation of the hair growth
cycle. This review focuses on the hormonal background of hair loss, including pathophysiology,
underlying endocrine disorders, and possible treatment options for alopecia. In particular, the
role of androgens, including dihydrotestosterone (DHT), testosterone (T), androstenedione (A4),
dehydroepiandrosterone (DHEA), and its sulfate (DHEAS), has been studied in the context of
androgenetic alopecia. Androgen excess may cause miniaturization of hair follicles (HFs) in the
scalp. Moreover, hair loss may occur in the case of estrogen deficiency, appearing naturally during
menopause. Also, thyroid hormones and thyroid dysfunctions are linked with the most common
types of alopecia, including telogen effluvium (TE), alopecia areata (AA), and androgenetic alopecia.
Particular emphasis is placed on the role of the hypothalamic–pituitary–adrenal axis hormones
(corticotropin-releasing hormone, adrenocorticotropic hormone (ACTH), cortisol) in stress-induced
alopecia. This article also briefly discusses hormonal therapies, including 5-alpha-reductase inhibitors
(finasteride, dutasteride), spironolactone, bicalutamide, estrogens, and others.
Keywords: hair loss; androgens; estrogens; thyroid hormones; growth hormone; corticotropin-releasing
hormone; androgenetic alopecia; polycystic ovary syndrome; alopecia areata; 5-alpha-reductase
1. Introduction
Hair loss is a common condition affecting both men and women and impacting the
majority of the population by age 80 [
1
]. Given that head hair plays a crucial role in the
perception of an ideal physique, hair loss can cause serious psychological distress [
2
].
Studies have shown the effects of alopecia on reduction in self-esteem, difficulties in
coping with stress, and the increased incidence of depression and anxiety disorders [
3
–
5
].
Emotional distress related to hair loss may occasionally be extremely intense, with cases of
suicide linked to hair loss that have been reported [
6
]. This risk is particularly significant
in patients with concomitant endocrinopathies, as these conditions may themselves cause
psychiatric disorders [7].
The hair growth process consists of three main phases: anagen, catagen, and telogen,
constituting growth, transition, and rest, respectively [
8
]. Some authors additionally
distinguish an exogen phase, during which hair shaft release is initiated and successfully
executed [
9
]. The hair cycle entails a complex interplay of various endocrine, autocrine,
and paracrine signaling pathways [
10
]. Hormones significantly impact the structure of
hair follicles and hair growth by influencing the hair cycle. Most notably, hair condition
is affected by the action of androgens, which bind to intracellular androgen receptors in
dermal papilla cells to affect the hair follicle. The impact of androgens on hair follicles
varies depending on the location of the hair on the body [
11
]. A genetically predisposed
Biomedicines 2024,12, 513. https://doi.org/10.3390/biomedicines12030513 https://www.mdpi.com/journal/biomedicines
Biomedicines 2024,12, 513 2 of 14
elevated sensitivity of hair follicles to androgens leads to androgenetic alopecia—the most
prevalent form of nonscarring hair loss [
12
]. Also, the impact of thyroid hormones (THs)
on hair growth has been a subject of particular study, with previous research providing
strong evidence linking THs to alopecia. In addition to androgens and thyroid hormones,
the impact of other hormones, such as estrogens, corticotropin-releasing factor (CRF; also
known as corticotropin-releasing hormone, CRH), adrenocorticotropic hormone (ACTH),
cortisol, and growth hormone (GH), on the process of hair growth, is currently being
studied [
11
]. Various hormonal disorders facilitate the shift from the anagen to the telogen
phase, potentially resulting in hair loss [
13
,
14
]. Considering the frequency of endocrine
disorders and the possibility that hair loss might serve as their sole clinical manifestation, it
is crucial to consider hormonal causes in the diagnosis of alopecia thoroughly.
Despite the widespread occurrence of hair loss, its heterogeneous etiology contributes
to limited diagnostic and therapeutic options in many cases. Hormonal changes play a
key role in the pathogenesis of many types of alopecia [
15
]. Hence, a review of the current
literature for endocrine causes is important to continuously update the comprehensive
clinical management of hair loss. This work offers current insight into hormonal impacts on
alopecia and highlights some of the emerging therapeutic options related to this condition.
2. Androgens
Androgens are one of the most important factors promoting hair growth both in
men and women [
16
,
17
]. The primary mechanism of their action involves binding to
the intracellular androgen receptor (AR) in dermal papilla cells (DPCs), which initiates
a signaling cascade, leading to the transformation of thin, short, and straight vellus hair
into dark, longer, and curly terminal hair. This process occurs in androgen-dependent
regions, including axillary and pubic areas in both sexes and the beard and trunk areas in
men [
16
,
17
]. Human androgens are produced mainly in gonads and adrenal glands, as well
as in other organs, including skin, adipose tissue, and the brain [
18
]. The most important
androgens synthesized in gonads are testosterone (T) and 5
α
-dihydrotestosterone (DHT),
whereas in adrenal glands, 4-androstenedione (A4), dehydroepiandrosterone (DHEA), and
its sulfate DHEAS are synthesized [
18
,
19
]. T and DHT are the principal and most potent
androgens involved in the hair growth process. T is the main androgen circulating in
the blood, while DHT is produced during the peripheral conversion of T by the enzyme
5
α
-reductase. Compared to T, DHT has a greater affinity for AR. Namely, DHT binds
to the AR approximately 4 to 5 times more strongly and dissociates 3 times slower than
T [12,20–22].
Although DHT promotes hair growth in androgen-dependent regions, its action in
hairy scalp skin is quite the opposite. Here, evidence shows that one of the causes of
hair loss is excess DHT. Increased activity of type II 5
α
-reductase, and thus an excessive
production of DHT, was observed in the hair follicles (HFs) of people with androgenetic
alopecia (AGA) [
12
,
22
]. AGA can be divided into male androgenetic alopecia (MAGA),
otherwise known as male-pattern hair loss (MPHL), and female androgenetic alopecia
(FAGA), otherwise known as female-pattern hair loss (FPHL) [
23
,
24
]. Excess DHT causes
the miniaturization of hair, reducing the anagen phase and increasing the telogen phase,
leading to hair loss and decreased hair density [
25
]. Typically, MPHL affects the frontal
scalp and vertex, and its characteristic feature is a receding hairline [
26
]. Occipital hairs
are usually insensitive to androgen excess due to AR methylation in DPCs located in the
occipital region [
12
,
22
]. The assessment of androgen levels is possible in serum, saliva, and
urine samples. However, the clinical interpretation of the measurements is complicated
because most androgens are bound to proteins, and, therefore, their action is not directly
related to their total serum concentrations. Some assays enable the measurement of free T;
however, to avoid laboratory inaccuracies, it is better to measure total testosterone and the
concentration of sex hormone-binding globulin (SHBG) [27].
Hair loss may also be one of the signs of androgen excess in women, along with
hirsutism and acne. FPHL affects the central parietal part of the scalp [
28
]. In most cases, it
Biomedicines 2024,12, 513 3 of 14
is connected with polycystic ovary syndrome (PCOS) [
29
]. However, the exact diagnosis
may sometimes be challenging, as late-onset non-classic congenital adrenal hyperplasia
(NC-CAH), due to 21-hydroxylase deficiency, may mimic the clinical and laboratory signs
and symptoms of PCOS. It is worth noting that the key laboratory marker differentiating
those two clinical entities is 17-hydroxyprogesterone (17-OHP), which is a precursor of A4.
It is usually normal or slightly elevated in PCOS but significantly higher in NC-CAH [30].
Androgenetic alopecia is reported in 42.5% of women with PCOS compared to 6% in the
general female population under 50 years [
31
]. In understanding the pathogenesis of
androgen excess in women, one has to consider that the sources of these hormones are
different in men and women. In contrast to testes in men, the ovaries, adrenal glands, and
peripheral tissues in women are responsible for androgen production and metabolism.
Dehydroepiandrosterone (DHEA), its sulfated ester DHEAS, and androstenedione (A4) are
produced in the adrenal cortex and converted into T and DHT in peripheral tissues and the
ovaries [
29
]. Typically, in PCOS-related AGA, mild-to-moderate elevations in serum T, A4,
and/or DHEAS are observed. However, it is worth mentioning that serum T is a parameter
susceptible to various factors and dependent, among others, on the concentration of SHBG.
Therefore, T levels are not always elevated in women with androgenetic alopecia. It has
been shown that 25% of women presenting androgen excess symptoms have normal T
levels but elevated A4 levels. A4, unlike T, is less dependent on SHBG concentration [
29
,
32
].
Interestingly, AGA severity in women is negatively correlated with serum SHBG levels,
which is explained by the fact that higher SHBG concentrations bind more testosterone,
lowering its free and active fraction. Consequently, this decreases the negative impact of
T on hair growth [
33
]. For this reason, total T measurement should be performed only in
line with the SHBG test, which helps estimate the amount of free testosterone. Of note is
that commercially available free testosterone assays have low sensitivity, and we do not
recommend their use. Therefore, if a hormonal cause of hair loss in women is suspected, the
following parameters should be determined in the early follicular phase (between days 2
and 5 of the menstrual cycle): LH, follicle-stimulating hormone (FSH), estradiol, T, DHEAS,
A4, SHBG, 17-OHP, prolactin and thyroid function tests [29].
Interestingly, some researchers suggest that there is a male equivalent of PCOS, and
one of the diagnostic criteria for this syndrome is early-onset AGA. To diagnose early-onset
AGA, alopecia must be equal to or greater than III grade in the Hamilton–Norwood scale
and occur at under 35 [
34
]. The Hamilton–Norwood scale is a seven-grade classification
of the severity of hair loss. At stage III, the first signs of clinically significant balding
appear. According to the original description by Norwood et al., most type III scalps have
deep frontotemporal recessions, which are usually symmetrical and are either bare or very
sparsely covered by hair. These recessions extend further posteriorly than a point which
lies approximately 2 cm anterior to a coronal line drawn between the external auditory
meatus [
35
,
36
]. Men with early-onset AGA may have increased DHEAS levels, decreased
SHBG levels, and worse gonadal steroidogenesis [
34
]. Increased DHEAS, along with
17-OHP, is a determinant of increased adrenal activity [37,38]. For details, see Table 1.
Biomedicines 2024,12, 513 4 of 14
Table 1. Hormonal changes in hair loss.
Hormone Hormone Level Possible Endocrine Disorder Type of Alopecia
Androgens
T
DHT
A4
DHEA
DHEAS
increased androgen excess
•polycystic ovary syndrome *
•
congenital adrenal hyperplasia *
•androgen-producing tumors
•androgenetic alopecia
SHBG decreased
FAI ** increased
Estrogens
E2 decreased menopause •female pattern hair loss
•
frontal fibrosing alopecia
Stress hormones
CRH increased chronic stress •stress-induced alopecia
•alopecia areata
ACTH increased/decreased *** Cushing disease •androgenetic alopecia
Cortisol increased
Thyroid hormones
T3
T4 decreased/increased hypothyroidism/hyperthyroidism
•telogen effluvium
•alopecia areata
•androgenetic alopecia
Others
GH decreased
GH deficiency
•Turner syndrome
•Noonan syndrome
•Prader–Willi syndrome
•androgenetic alopecia
•telogen effluvium
Abbreviations: T—testosterone, DHT—dihydrotestosterone, A4—4-androstenedione, DHEA—dehydroepiandrosterone,
DHEAS—dehydroepiandrosterone-sulfate, SHBG—sex hormone-binding globulin, FAI—free androgen index, E2—
estradiol, CRH—corticotropin-releasing hormone, ACTH—adrenocorticotropic hormone, T3—triiodothyronine, T4—
thyroxine, GH—growth hormone. * In the differentiation between polycystic ovary syndrome and congenital adrenal
hyperplasia, 17-hydroxyprogesterone (17-OHP) is useful (increased in congenital adrenal hyperplasia vs. normal or
slightly increased in PCOS). ** Free androgen index (FAI) = total testosterone level/sex hormone-binding globulin level.
*** Increased in pituitary adenoma; decreased in adrenal tumor.
The US Food and Drug Administration (FDA) approved two drugs for AGA treatment,
namely, topical minoxidil and oral finasteride; however, the latter one is only approved for
MAGA. The action of finasteride is strictly connected with androgens, as it is a 5
α
-reductase
type II inhibitor that blocks the production of DHT. A daily dose of 1 mg oral finasteride in
MAGA enables a reduction in scalp and serum DHT by 60% [
39
]. It also shows effectiveness
in FPHL, especially when used at a higher dosage (5 mg/d) for at least a year. However,
despite its efficacy, it is not approved by the FDA in women due to its adverse hormonal
effects [
40
]. Hence, first-line therapy in FPHL includes 5% minoxidil, a non-hormonal va-
sodilator. In second-line therapy, finasteride and other antiandrogenics may be considered
off-label, especially when hair loss is severe or in women with hyperandrogenism [
41
].
Another 5
α
-reductase inhibitor, which is used off-label in AGA treatment, is dutasteride.
A recent meta-analysis showed that 0.5 mg of dutasteride daily is more effective in AGA
treatment than 1 mg of finasteride daily. However, this difference disappeared after a higher
dosage of finasteride (5 mg daily) [
42
]. There are also other non-FDA-approved treatments
Biomedicines 2024,12, 513 5 of 14
that show effectiveness in patients with AGA. These include, among others, hormonal ther-
apies with antiandrogenic effects: oral spironolactone, bicalutamide, cyproterone acetate
(CA), and topical androgen receptor inhibitors: clascoterone and pyrilutamide [
23
,
26
,
43
,
44
].
Spironolactone, a synthetic aldosterone receptor antagonist, also acts as an AR antagonist
and decreases total testosterone levels by blocking adrenal enzymes involved in the synthe-
sis of T (17
α
-hydroxylase and desmolase) [
45
,
46
]. It is used in the treatment of FPHL with
an overall hair loss improvement rate reaching 56.60%, as reported in a recent meta-analysis.
Importantly, better results were obtained in a combined therapy group (oral spironolactone
and minoxidil) in comparison with monotherapy (65.80% and 43.21%, respectively) [
47
].
The standard dose of spironolactone is 100–200 mg daily; however, doses range from 25–200
mg daily [
26
]. Bicalutamide is an emergent selective AR antagonist with favorable safety
and reduction in hair loss severity by 24.5% at a 1-year measurement (measurement in
Sinclair scale). Studies suggest efficient doses are 10–50 mg daily [
48
–
50
]. There are also
natural antiandrogens proposed in AGA therapy. One of them is pumpkin seed oil, which
blocks 5
α
-reductase. Mean hair count increased by 40% in the group of men treated with
pumpkin seed oil at 24 weeks, compared with 10% in the placebo-treated group [
21
,
51
,
52
].
Moreover, topical pumpkin seed oil did not have significant adverse effects in comparison
with the side effects of finasteride and minoxidil [53,54]. For details, see Table 2.
Table 2. Hormonal treatments in hair loss.
Medication Mechanism of Action Route of
Administration Dose Indication
Finasteride 5α-reductase type II
inhibitor
oral 1 mg daily
Androgenetic alopecia
topical 0.25% solution
(1 mL twice daily)
Dutasteride
5
α
-reductase type I and
II inhibitor oral 0.5 mg daily
Spironolactone
AR * antagonist,
17α-hydroxylase
inhibitor
oral 25–200 mg daily
topical 1% gel or 5% solution
twice daily
Bicalutamide AR antagonist oral 10–50 mg daily
Cyproterone acetate
5α-reductase inhibitor,
AR antagonist,
gonadotrophin
secretion inhibitor
oral 50 mg daily
Clascoterone AR antagonist topical 1% cream
Pyrilutamide AR antagonist topical
0.5% solution
(1 mL once/twice
daily)
Pumpkin seed oil Herbal 5α-reductase
inhibitor oral 400 mg daily
Estradiol
ER agonist,
elevation of sex
hormone-binding
globulin levels
oral 1–2 mg daily
menopause,
premature ovarian
failure
Levothyroxine Synthetic version of
human thyroxine oral 25–200 µg daily hypothyroidism
* AR—androgen receptor.
3. Estrogens
Human estrogens include estrone, estradiol, and estriol, with estradiol being the most
potent. Estrogens exert their effects through two receptors, ER-
α
and ER-
β
, with the latter
Biomedicines 2024,12, 513 6 of 14
being observed in hair follicles [
55
]. Binding with ER-
β
, estrogens can substantially modify
the growth and life cycle of the hair follicle by exerting influence on the aromatase activity
responsible for converting androgens into estrogens. Particularly, estradiol extends the
anagen phase of the hair cycle, amplifying hair growth through the augmented synthesis of
growth factors that stimulate the proliferation of keratinocytes of the outer root sheath [
56
].
Consequently, estrogens are assumed to promote hair growth, increase hair diameter, and
prevent hair loss [13].
A decrease in estrogen levels below their physiological concentration is known as hy-
poestrogenism. Various conditions can result in hypoestrogenism, including menopause (the
most common cause), premature ovarian failure, and other causes of hypogonadism [
57
–
59
].
In previous studies, the relationship between menopause and hair loss has been studied and
described in particular [
60
,
61
]. Estrogens in premenopausal non-pregnant women are mainly
synthesized in the ovaries. After menopause, when the hormonal activity of the ovaries is lost,
the main site of estrogen production shifts from the ovaries to peripheral tissues such as the
skin, adipose tissue, bone, and brain. For that reason, amid all hormonal changes associated
with menopause, one central process that occurs is a significant decline in estrogen levels [
62
].
In line with this, the protective role of estrogens against hair loss has been assumed based
on phenomena of diminished hair renewal, growth, thickness, and hair rarefaction observed
during the menopausal period [
56
]. This function of estrogens is further supported by the ob-
servation that the frontal hairline typically remains unaffected in female pattern androgenetic
alopecia; this is explained by a relatively high level of aromatase in the frontal hairline region
of the scalp. Aromatase is the enzyme responsible for converting testosterone to estradiol and
androstenedione to estrone; thus, high levels of this enzyme lower the amounts of androgens
and enrich the estrogen supplies to this part of the skin [
63
]. Nevertheless, it should be noted
that the decline in estrogen levels associated with menopause induces hair loss only in some
women. Other factors affecting hair health include diet, stress, genetic factors, chronic health
issues, use of medications, and nutritional deficiencies [
64
]. Additionally, the estrogens-to-
androgen ratio may be responsible for alopecia in female-pattern hair loss rather than the
absolute values of either hormone [65]. These findings require further studies.
Considering the above-mentioned physiological background, hormonal therapies
containing estrogens are believed to exert independent regulatory effects on hair growth
and to address androgen-dependent disorders through indirect mechanisms that impede
androgenic actions. These mechanisms involve the elevation of sex hormone-binding
globulin levels, consequently diminishing the availability of androgens [
66
]. Improvement
in the frontal hairline thinning score and increase in the plucking strength resulting from
6 months of hormone replacement therapy was revealed [
67
]. Nevertheless, precaution
is imperative in the prescription of hormonal therapies, as estrogens have been linked to
heightened susceptibility to cardiovascular events, stroke, venous thromboembolic events,
and breast cancer [66].
The management of alopecia may be particularly complex in women diagnosed with
breast cancer, being the most common malignancy in women globally [
68
]. Hormonal
therapy currently constitutes the basic treatment of early-stage breast cancer. Tamoxifen
(acting as a selective estrogen receptor modulator), as well as aromatase inhibitors and
ovarian function suppression (which lower estrogen levels), administered individually
and in combination, significantly reduce recurrence and mortality [
69
]. The inhibition
of androgen-to-estrogen conversion may lead to oncotherapy-induced alopecia, which
clinically resembles female androgenetic alopecia. Additionally, hair loss can be exacerbated
by the high-stress level associated with a cancer diagnosis. Moreover, due to the elevation
of sebaceous glands secretion, the texture and appearance of the hair changes. Treatment
options for oncotherapy-induced alopecia are limited, as 17
β
-estradiol should not be used
in these patients due to its ability to bind to estrogen receptors. On the other hand, 17
α
-
estradiol does not bind to estrogen receptors but may increase the conversion of testosterone
to 17
β
-estradiol, presumably by increasing aromatase activity; therefore, this treatment
may also pose potential risks to patients with hormone receptor-positive breast cancer [
70
].
Biomedicines 2024,12, 513 7 of 14
Therefore, in the potential treatment of alopecia in breast cancer patients, spironolactone,
acting as an antagonist of the androgen receptor (as described above), might be considered.
The potential safety of spironolactone may be attributed to the fact that it has been shown
not to increase estrogen levels in most patients. Studies involving 49,298 patients did not
consistently show evidence of an elevated risk of female breast cancer associated with the
use of spironolactone [71].
Hair loss linked to estrogenic activity may also be a manifestation of COVID-19. Estro-
gens demonstrate anti-inflammatory effects through the inhibition of pro-inflammatory
cytokines. During the infection, the depletion of estrogens diminishes their protective
function on hair follicles, contributing to hair loss [
72
]. Further research on the correlation
between COVID-19 as well as other diseases affecting the immune system, with a partic-
ular focus on postmenopausal women with permanent reduction in levels of estradiol,
is needed.
4. ACTH, CRH, and Cortisol
Evidence shows that stress can induce hair loss by acting through stress hormones [
73
–
77
]. Corticotropin-releasing factor (CRF), adrenocorticotropic hormone (ACTH), and cor-
tisol belong to the main stress hormones in humans and constitute the elements of the
hypothalamic–pituitary–adrenal axis [
78
]. CRF is secreted by the paraventricular nucleus
of the hypothalamus under numerous stressors and plays a pivotal role in the regulation of
the stress response, as it activates the HPA axis and promotes the synthesis of ACTH by the
pituitary gland. ACTH stimulates the adrenal cortex to produce and release glucocorticoids,
such as cortisol [
78
,
79
]. Receptors for cortisol and CRF are found, among others, in the
skin [
74
]. Interestingly, some researchers suggest that human DPCs have a fully functional
HPA axis and are able not only to respond to CRF but also toexpress CRF and its receptors [
73
].
Under stress conditions, CRF binds to its receptors located in hair follicle cells (DPCs and
outer root sheath cells), which causes early catagen transition and the inhibition of hair shaft
elongation. The molecular mechanisms of CRF action in DPCs involve increased intracellular
concentration of reactive oxygen species (ROS) with subsequent apoptosis, cell cycle arrest
at the G2/M phase, and downregulation of anagen-related cytokine levels. Consequently,
increased CRF levels in hair follicle cells may result in hair loss [
73
,
80
]. Moreover, in the
DPCs influenced by CRF, higher levels of other HPA hormones, such as cortisol, ACTH, and
its precursor proopiomelanocortin (POMC), were observed. This effect may be connected
with the upregulation of POMC gene expression and stimulation of POMC conversions by
CRF [
11
]. This study also showed that CRF receptor antagonists blocked the HPA axis in the
DPCs [73].
Dysfunctional cutaneous HPA axis might be one of the underlying causes of alopecia
areata. Elevated CRH, ACTH, and
α
-melanocyte-stimulating hormone (
α
-MSH) levels
were observed in HFs and the scalp epidermis of patients with AA [
79
,
81
]. Above all, CRH
(along with substance P) may initiate AA. This involves two mechanisms: autoimmune and
apoptotic. The autoimmune pathway dominates and is based on the collapse in the immune
privilege of HFs. HFs begin to show a higher expression of major histocompatibility
(MHC) class antigens and become a target for the immune system [
76
,
79
,
82
]. Some studies
in vitro
suggest a restoration of the immune privilege of HFs in the treatment of AA.
They propose
α
-MSH, ACTH, and
β
-endorphin as immunomodulators acting through the
suppression of the excessive expression of MHC class I [
83
]. Other studies suggest that
the immunosuppressive function of ACTH and MSH may be restored thanks to UVA-1
treatment. The effect depends on the interruption of excessive CRH stimulation and the
normalization of the HPA axis [84]. This field requires further studies [76].
Androgenetic alopecia is another hair loss type that might be connected with stress.
Fischer et al. proved that CRH promoted a complex stress response in the HFs of patients
with AGA. Researchers found increased expression of CRH receptors 1 and 2 (CRH-
R1/2), ACTH, catagen-inducing transforming growth factor-
β
2 (TGF-
β
2), melanocortin
receptor 2 (MC-R2), and other parameters associated with stress (substance P and p75
Biomedicines 2024,12, 513 8 of 14
neurotrophin receptor). Moreover, in the HFs incubated with CRH, the expression of
anagen-promoting insulin-like growth factor-1 (IGF-1) and matrix keratinocyte proliferation
was significantly lower than in controls. Interestingly, the effects mentioned above were
blocked by caffeine [76,85].
The role of cortisol in the pathogenesis of alopecia still remains unclear. It has been
shown that high levels of cortisol can cause premature degradation and reduced syn-
thesis of hyaluronan and proteoglycans located in the skin, which may negatively affect
HFs [
11
,
13
,
76
,
86
]. Moreover, increased levels of cortisol were observed in patients with
AGA compared to healthy individuals [
13
,
87
]. Thus, some studies put forward cortisol
inhibitors as potential therapeutic options for patients with AGA [
13
,
88
,
89
]. Ketoconazole
is an antifungal drug that blocks numerous enzymes, including 21-hydroxylase, a key
enzyme in cortisol synthesis [
90
]. Additionally, it has antiandrogenic properties at high
concentrations, thanks to the inhibition of enzymes involved in androgen synthesis and the
competitive blockage of AR. Topical 2% ketoconazole provides a high local concentration
in HF and allows for telogen-to-anagen transition [
91
,
92
]. Hence, topical ketoconazole is
considered to be an alternative therapy for patients with AGA after first-line treatments
of finasteride and minoxidil [
89
]. The target of this therapy is to stimulate proteoglycan
synthesis and consequently counteract hair loss. Increased hair shaft diameter and hair
regrowth were described in some studies; however, the evidence is limited, and further
randomized controlled trials are needed in this field [
13
,
89
]. On the other hand, low cortisol
levels can positively impact hair growth by delaying proteoglycan degeneration [
11
,
76
,
86
].
Furthermore, corticosteroids are used as a treatment in AA [
93
–
95
]. Topical corticosteroids
and pulse dose corticosteroid therapy also show effectiveness in pediatric AA [96,97].
The assessment of cortisol levels may be a useful diagnostic tool in clinical practice [
11
,
98
].
Cortisol levels fluctuate during the day and can be measured in saliva samples [13,99].
Diurnal cortisol slope testing has not been particularly researched in relation to hair
loss, although it may be used to evaluate the HPA axis’ balance and the impact of stress.
Another promising method indicating chronic stress involves hair cortisol concentration
measurements. Unfortunately, there are not enough data to currently confirm the utility of
this method in patients with alopecia [13].
5. Thyroid Hormones
Thyroid hormones regulate numerous cellular activities, including the endogenous
modulation of dermal proliferation and local inflammation [
16
,
100
]. They are also required
for hair follicles’ physiological growth and maintenance [
16
]. During embryonic develop-
ment, thyroid hormones control hair follicle differentiation and growth. THs impact both
the anagen and telogen phases—they stimulate cell proliferation and metabolic activity
within the HFs, which promotes the beginning and maintenance of the anagen phase;
they also regulate the length of the telogen phase. These hormones also stimulate the
production and distribution of melanin [
100
,
101
]. Hair loss is observed in patients with
hypothyroidism or hyperthyroidism [
100
], but the hair condition is induced through differ-
ent mechanisms. Hypothyroidism impedes epidermal and skin appendage cell division,
decreasing anagen frequency [
16
,
100
]. On the other hand, hyperthyroidism results in
oxidative damage. It increases free radical formation in mitochondria due to the stimulated
production of reactive oxygen species. Still, the exact mechanism of its impact on hair loss
remains not fully understood [
100
]. The thyroid profile is linked with the most common
types of alopecia, including telogen effluvium (TE), alopecia areata (AA), androgenetic
alopecia, and hair changes associated with thyroid malignancies, and those connections are
elucidated below.
5.1. Autoimmune Thyroid Disorders
In patients with alopecia areata, there is a higher prevalence of autoimmune conditions,
such as Hashimoto’s thyroiditis and Graves’s disease. Also, a higher incidence of anti-
thyroid antibodies, including anti-thyroid peroxidase, antithyroglobulin, and TSH-receptor
Biomedicines 2024,12, 513 9 of 14
antibodies, is observed in this group of patients compared to the control. Approximately
5% of AA patients have subclinical hypothyroidism related to Hashimoto’s thyroiditis, and
a significant proportion experience some form of thyroid dysfunction. Moreover, a female
predominance is observed. There is also an immunological association between thyroid
illnesses and AA—certain HLA types are connected to both AA and antibody-induced
hypothyroidism. On the other hand, regulatory T cells are involved in both AA and thyroid
condition progression. In line with this, some studies demonstrate a higher likelihood
of AA in patients suffering from autoimmune hyperthyroidism or hypothyroidism as
compared with healthy controls [100,102].
Autoimmune thyroid disorders may also be associated with MPA. For example, a
study on 1232 men and women for 25 months identified 14.29% (n= 176) of them with
MPA. The prevalence of thyroid dysfunctions in the MPA subgroup differed with age as
follows: 6.3% in patients below 20 years old, 17% in persons aged between 21 and 40 years,
and 50% in individuals older than 40 years [102].
5.2. Hypothyroidism and Hyperthyroidism
Unlike alopecia areata, telogen effluvium is linked to the thyroid hormones’ blood-
stream levels and not to autoimmune conditions [
102
]. As T3 and T4 affect the follicles
directly and make them sensitive during anagen, their low blood levels in hypothyroidism
may lead to hair loss with prolonged shedding and also changes in hair texture [
100
]. One
of the most recently published study results confirms the significant association between
hypothyroidism and TE by pointing out the fact that hypothyroidism is a common under-
lying cause of TE. The prolonged telogen phase, associated with hypothyroidism, results in
the typical hair loss seen in TE [103].
Moreover, a considerable prevalence of hypothyroidism is observed in patients with
frontal fibrosing alopecia. According to data from a study conducted on patients with this
type of hair loss, hypothyroidism was present in 22.9% of patients [104].
Some data indicate the connection between female pattern hair loss and hypothy-
roidism. In a prospective study conducted on FPHL patients aged 20 to 88 years, hypothy-
roidism was observed in 31.25% of individuals, but there was no correlation between the
severity of hair loss and the presence of thyroid disease. More evidence is needed to define
whether the increasing prevalence of thyroid disorders in this population is incidental or
represents a part of a pathogenic mechanism [100,102].
According to the findings above, the thyroid profile should be checked in patients
with hair loss to implement proper hormonal treatment in case of thyroid disorders and
in order to improve alopecia treatment. The standard treatment for hypothyroidism is
levothyroxine, administered orally, and after restoring normal thyroid function, it results in
the effective relief of hypothyroidism symptoms in the majority of patients. In line with
this, the hair loss caused by hypothyroidism usually improves within several months [
105
].
Hyperthyroidism may cause diffuse scalp hair thinning. Moreover, according to some
authors, hair loss is observed in about 50% of hyperthyroid patients [
100
]. Hyperthyroidism
treatment includes antithyroid drugs, radioiodine treatment, and surgery. Antithyroid
drugs include methimazole and propylthiouracil, administered orally, usually for several
months until the restoration of correct thyroid hormone levels. Upon achieving normal
thyroid hormone levels, the underlying cause of hair loss disappears, and as a result, the
condition of hair should improve. This may not happen if there is another coexisting
pathology, including immune-mediated hair disorders that may be a complication of
autoimmune hyperthyroidism [
106
]. On the other hand, side effects of antithyroid drugs
include hair loss, which may further deteriorate the condition of hair. For this reason,
therapy should always be individually targeted.
5.3. Hair Changes Associated with Thyroid Malignancies
There are a few potential ways in which hair may be affected when it comes to thyroid
cancer. Individuals with thyroid malignancies may sometimes experience hair loss or
Biomedicines 2024,12, 513 10 of 14
thinning hair. This hair loss is not exclusive to the scalp and can also affect other body
hair. Because of thyroid dysfunction in the course of thyroid cancer, changes in hair texture
may be observed too [
100
,
107
]. Also, it is worth mentioning a systematic review of 123
individuals with histologically confirmed alopecia neoplastica (AN) that identified 7.3%
(9/123) of them with a thyroid malignancy; 66.7% (6/9) were females [
102
]. Still, the
amount of statistical evidence is low, and further investigation is needed for this junction
to be better understood. Moreover, in rare cases, changes in hair color due to disrupted
melanin production in patients with thyroid malignancies may be observed, which can
involve a darkening or lightening of the hair [100,108].
6. Growth Hormone (GH)
Although growth hormone receptors have been found in the human hair follicle, the
exact role of growth hormone in HF physiology remains unexplored. In general, in GH
deficiency, dermatologic manifestations are observed, including alopecia, frontal hairline
recession, and telogen effluvium. Moreover, it is associated with severe HF structural
changes like pili torti et canaliculi and trichorrhexis nodosa [
109
–
111
]. In pathologies leading
to GH deficiency, like Noonan syndrome, Turner syndrome, and Prader–Willi syndrome,
alopecia, telogen effluvium, and frontline hair recession are observed [
109
,
111
]. Unexpect-
edly, ex vivo stimulation of GH receptors in human HFs results in hair growth inhibition
in the female human scalp. Furthermore, primary decreases in GH and IGF-1 have been
associated with hair loss and alopecia, while decreases in GH and IGF-1 due to GHRH
deficiency have not [109,112,113].
Undoubtedly, a better understanding of the growth hormone effect on the HF, skin,
and related signaling pathways (with potential sex differences taken into consideration)
would be crucial to implementing new therapies for dermatopathology.
7. Conclusions
Hair loss, considering its significant prevalence, diverse causes, and both physical and
psychological impact, should be understood as a serious health problem that requires a
proper diagnostic process. It can also be a sign of underlying internal disease, including
disorders of the endocrine system, in particular, the thyroid, ovaries, testes, adrenal glands,
and pituitary gland, as discussed in this review. We believe that the link between this
dermatological manifestation and endocrine disorders cannot be ignored, and hair loss
investigation may lead to the correct diagnosis of the underlying endocrine disease, thereby
allowing for proper treatment to be provided and allowing for improvement of both hair
status and the internal condition of the patient.
Author Contributions: Conceptualization, B.O., A.T., K.D. and M.O.; writing—original draft prepa-
ration, B.O., A.T. and K.D.; writing—review and editing, M.O.; visualization, B.O.; supervision, M.O.
All authors have read and agreed to the published version of the manuscript.
Funding: This research received no external funding.
Conflicts of Interest: The authors declare no conflicts of interest.
References
1.
Santos, Z.; Avci, P.; Hamblin, M.R. Drug Discovery for Alopecia: Gone Today, Hair Tomorrow. Expert Opin. Drug Discov. 2015,10,
269–292. [CrossRef]
2.
Aukerman, E.L.; Jafferany, M. The Psychological Consequences of Androgenetic Alopecia: A Systematic Review. J. Cosmet.
Dermatol. 2023,22, 89–95. [CrossRef]
3.
Monselise, A.; Bar-On, R.; Chan, L.; Leibushor, N.; McElwee, K.; Shapiro, J. Examining the Relationship between Alopecia Areata,
Androgenetic Alopecia, and Emotional Intelligence. J. Cutan. Med. Surg. 2013,17, 46–51. [CrossRef]
4. Dhami, L. Psychology of Hair Loss Patients and Importance of Counseling. Indian J. Plast. Surg. 2021,54, 411–415. [CrossRef]
5.
Russo, P.M.; Fino, E.; Mancini, C.; Mazzetti, M.; Starace, M.; Piraccini, B.M. HrQoL in Hair Loss-Affected Patients with Alopecia
Areata, Androgenetic Alopecia and Telogen Effluvium: The Role of Personality Traits and Psychosocial Anxiety. J. Eur. Acad.
Dermatol. Venereol. 2019,33, 608–611. [CrossRef]
6. Sinclair, R.D. Alopecia Areata and Suicide of Children. Med. J. Aust. 2014,200, 145. [CrossRef] [PubMed]
Biomedicines 2024,12, 513 11 of 14
7. Shoib, S.; Ahmad, J.; Rashid, A.; Shah, H.; Mushtaq, R.; Malik, M. Psychiatric Aspects in Endocrinolgical Disorders: Identifying
Depressive and Anxiety in Endocrine Patients Attending Outpatient Department—A Study from General Hospital in Kashmir
(India). Br. J. Med. Pract. 2016,9, a926.
8. Hoover, E.; Alhajj, M.; Flores, J.L. Physiology, Hair. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2024.
9.
Guarrera, M.; Rebora, A. Exogen Hairs in Women with and without Hair Loss. Ski. Appendage Disord 2017,3, 193–196. [CrossRef]
[PubMed]
10. Wall, D.; Meah, N.; Fagan, N.; York, K.; Sinclair, R. Advances in Hair Growth. Fac. Rev. 2022,11, 1. [CrossRef] [PubMed]
11.
Grymowicz, M.; Rudnicka, E.; Podfigurna, A.; Napierala, P.; Smolarczyk, R.; Smolarczyk, K.; Meczekalski, B. Hormonal Effects on
Hair Follicles. Int. J. Mol. Sci. 2020,21, E5342. [CrossRef] [PubMed]
12.
Ntshingila, S.; Oputu, O.; Arowolo, A.T.; Khumalo, N.P. Androgenetic Alopecia: An Update. JAAD Int. 2023,13, 150–158.
[CrossRef]
13.
Natarelli, N.; Gahoonia, N.; Sivamani, R.K. Integrative and Mechanistic Approach to the Hair Growth Cycle and Hair Loss. J.
Clin. Med. 2023,12, 893. [CrossRef]
14.
Gentile, P.; Garcovich, S. Advances in Regenerative Stem Cell Therapy in Androgenic Alopecia and Hair Loss: Wnt Pathway,
Growth-Factor, and Mesenchymal Stem Cell Signaling Impact Analysis on Cell Growth and Hair Follicle Development. Cells
2019,8, 466. [CrossRef] [PubMed]
15.
Alessandrini, A.; Bruni, F.; Piraccini, B.M.; Starace, M. Common Causes of Hair Loss—Clinical Manifestations, Trichoscopy and
Therapy. J. Eur. Acad. Dermatol. Venereol. 2021,35, 629–640. [CrossRef] [PubMed]
16.
Hasan, R.; Juma, H.; Eid, F.A.; Alaswad, H.A.; Ali, W.M.; Aladraj, F.J. Effects of Hormones and Endocrine Disorders on Hair
Growth. Cureus 2022,14, e32726. [CrossRef] [PubMed]
17.
Mason, K.A.; Schoelwer, M.J.; Rogol, A.D. Androgens During Infancy, Childhood, and Adolescence: Physiology and Use in
Clinical Practice. Endocr. Rev. 2020,41, bnaa003. [CrossRef]
18.
Alemany, M. The Roles of Androgens in Humans: Biology, Metabolic Regulation and Health. Int. J. Mol. Sci. 2022,23, 11952.
[CrossRef] [PubMed]
19.
Bienenfeld, A.; Azarchi, S.; Lo Sicco, K.; Marchbein, S.; Shapiro, J.; Nagler, A.R. Androgens in Women: Androgen-Mediated Skin
Disease and Patient Evaluation. J. Am. Acad. Dermatol. 2019,80, 1497–1506. [CrossRef] [PubMed]
20.
Swerdloff, R.S.; Dudley, R.E.; Page, S.T.; Wang, C.; Salameh, W.A. Dihydrotestosterone: Biochemistry, Physiology, and Clinical
Implications of Elevated Blood Levels. Endocr. Rev. 2017,38, 220–254. [CrossRef] [PubMed]
21.
Dhariwala, M.Y.; Ravikumar, P. An Overview of Herbal Alternatives in Androgenetic Alopecia. J. Cosmet. Dermatol. 2019,18,
966–975. [CrossRef]
22.
Tai, T.; Kochhar, A. Physiology and Medical Treatments for Alopecia. Facial Plast. Surg. Clin. N. Am. 2020,28, 149–159. [CrossRef]
23.
Devjani, S.; Ezemma, O.; Kelley, K.J.; Stratton, E.; Senna, M. Androgenetic Alopecia: Therapy Update. Drugs 2023,83, 701–715.
[CrossRef]
24.
Starace, M.; Orlando, G.; Alessandrini, A.; Piraccini, B.M. Female Androgenetic Alopecia: An Update on Diagnosis and
Management. Am. J. Clin. Dermatol. 2020,21, 69–84. [CrossRef] [PubMed]
25.
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. [CrossRef]
26.
Nestor, M.S.; Ablon, G.; Gade, A.; Han, H.; Fischer, D.L. Treatment Options for Androgenetic Alopecia: Efficacy, Side Effects,
Compliance, Financial Considerations, and Ethics. J. Cosmet. Dermatol. 2021,20, 3759–3781. [CrossRef] [PubMed]
27.
Heijboer, A.C.; Hannema, S.E. Androgen Excess and Deficiency: Analytical and Diagnostic Approaches. Clin. Chem. 2023,69,
1361–1373. [CrossRef] [PubMed]
28.
Müller Ramos, P.; Melo, D.F.; Radwanski, H.; de Almeida, R.F.C.; Miot, H.A. Female-Pattern Hair Loss: Therapeutic Update. Bras.
Dermatol. 2023,98, 506–519. [CrossRef] [PubMed]
29.
Cussen, L.; McDonnell, T.; Bennett, G.; Thompson, C.J.; Sherlock, M.; O’Reilly, M.W. Approach to Androgen Excess in Women:
Clinical and Biochemical Insights. Clin. Endocrinol. 2022,97, 174–186. [CrossRef] [PubMed]
30.
Papadakis, G.; Kandaraki, E.A.; Tseniklidi, E.; Papalou, O.; Diamanti-Kandarakis, E. Polycystic Ovary Syndrome and NC-CAH:
Distinct Characteristics and Common Findings. A Systematic Review. Front. Endocrinol. 2019,10, 388. [CrossRef]
31.
Abusailik, M.A.; Muhanna, A.M.; Almuhisen, A.A.; Alhasanat, A.M.; Alshamaseen, A.M.; Bani Mustafa, S.M.; Nawaiseh, M.B.
Cutaneous Manifestation of Polycystic Ovary Syndrome. Dermatol. Rep. 2021,13, 8799. [CrossRef]
32.
O’Reilly, M.W.; Taylor, A.E.; Crabtree, N.J.; Hughes, B.A.; Capper, F.; Crowley, R.K.; Stewart, P.M.; Tomlinson, J.W.; Arlt, W.
Hyperandrogenemia Predicts Metabolic Phenotype in Polycystic Ovary Syndrome: The Utility of Serum Androstenedione. J.
Clin. Endocrinol. Metab. 2014,99, 1027–1036. [CrossRef] [PubMed]
33.
Chen, Q.; Tao, Q.; Zhu, Q.; Zhu, J.; Du, X. Association Between Trichoscopic Features and Serum Hormone Levels and Vitamin D
Concentration in Patients with Androgenetic Alopecia in Eastern China: A Cross-Sectional Study. Clin. Cosmet. Investig. Dermatol.
2023,16, 2547–2555. [CrossRef] [PubMed]
34.
Cannarella, R.; Condorelli, R.A.; Dall’Oglio, F.; La Vignera, S.; Mongioì, L.M.; Micali, G.; Calogero, A.E. Increased DHEAS
and Decreased Total Testosterone Serum Levels in a Subset of Men with Early-Onset Androgenetic Alopecia: Does a Male
PCOS-Equivalent Exist? Int. J. Endocrinol. 2020,2020, 1942126. [CrossRef] [PubMed]
35. Hamilton, J.B. Patterned Loss of Hair in Man; Types and Incidence. Ann. N. Y. Acad. Sci. 1951,53, 708–728. [CrossRef]
Biomedicines 2024,12, 513 12 of 14
36. Norwood, O.T. Male Pattern Baldness: Classification and Incidence. South Med. J. 1975,68, 1359–1365. [CrossRef]
37.
Stárka, L.; Dušková, M. Remarks on the Hormonal Background of the Male Equivalent of Polycystic Ovary Syndrome. Prague
Med. Rep. 2021,122, 73–79. [CrossRef]
38.
Di Guardo, F.; Ciotta, L.; Monteleone, M.; Palumbo, M. Male Equivalent Polycystic Ovarian Syndrome: Hormonal, Metabolic,
and Clinical Aspects. Int. J. Fertil. Steril. 2020,14, 79–83. [CrossRef]
39.
York, K.; Meah, N.; Bhoyrul, B.; Sinclair, R. A Review of the Treatment of Male Pattern Hair Loss. Expert Opin. Pharmacother. 2020,
21, 603–612. [CrossRef]
40.
Nobari, N.N.; Roohaninasab, M.; Sadeghzadeh-Bazargan, A.; Goodarzi, A.; Behrangi, E.; Nikkhah, F.; Ghassemi, M. A Systematic
Review of Clinical Trials Using Single or Combination Therapy of Oral or Topical Finasteride for Women in Reproductive Age
and Postmenopausal Women with Hormonal and Nonhormonal Androgenetic Alopecia. Adv. Clin. Exp. Med. 2023,32, 813–823.
[CrossRef]
41.
Carmina, E.; Azziz, R.; Bergfeld, W.; Escobar-Morreale, H.F.; Futterweit, W.; Huddleston, H.; Lobo, R.; Olsen, E. Female Pattern
Hair Loss and Androgen Excess: A Report From the Multidisciplinary Androgen Excess and PCOS Committee. J. Clin. Endocrinol.
Metab. 2019,104, 2875–2891. [CrossRef]
42.
Gupta, A.K.; Venkataraman, M.; Talukder, M.; Bamimore, M.A. Relative Efficacy of Minoxidil and the 5-
α
Reductase Inhibitors in
Androgenetic Alopecia Treatment of Male Patients: A Network Meta-Analysis. JAMA Dermatol. 2022,158, 266–274. [CrossRef]
[PubMed]
43.
Azarchi, S.; Bienenfeld, A.; Lo Sicco, K.; Marchbein, S.; Shapiro, J.; Nagler, A.R. Androgens in Women: Hormone-Modulating
Therapies for Skin Disease. J. Am. Acad. Dermatol. 2019,80, 1509–1521. [CrossRef] [PubMed]
44.
Deoghare, S.; Sadick, N.S. Combination Therapy in Female Pattern Hair Loss. J. Cosmet. Laser Ther. 2023,25, 1–6. [CrossRef]
[PubMed]
45.
Aguilar Medina, D.A.; Cazarín, J.; Magaña, M. Spironolactone in Dermatology. Dermatol. Ther. 2022,35, e15321. [CrossRef]
[PubMed]
46.
Wang, C.; Du, Y.; Bi, L.; Lin, X.; Zhao, M.; Fan, W. The Efficacy and Safety of Oral and Topical Spironolactone in Androgenetic
Alopecia Treatment: A Systematic Review. Clin. Cosmet. Investig. Dermatol. 2023,16, 603–612. [CrossRef] [PubMed]
47.
Aleissa, M. The Efficacy and Safety of Oral Spironolactone in the Treatment of Female Pattern Hair Loss: A Systematic Review
and Meta-Analysis. Cureus 2023,15, e43559. [CrossRef] [PubMed]
48.
Carvalho, R.D.M.; Santos, L.D.N.; Ramos, P.M.; Machado, C.J.; Acioly, P.; Frattini, S.C.; Barcaui, C.B.; Donda, A.L.V.; Melo, D.F.
Bicalutamide and the New Perspectives for Female Pattern Hair Loss Treatment: What Dermatologists Should Know. J. Cosmet.
Dermatol. 2022,21, 4171–4175. [CrossRef]
49.
Fernandez-Nieto, D.; Saceda-Corralo, D.; Jimenez-Cauhe, J.; Moreno-Arrones, O.M.; Rodrigues-Barata, R.; Hermosa-Gelbard, A.;
Vano-Galvan, S. Bicalutamide: A Potential New Oral Antiandrogenic Drug for Female Pattern Hair Loss. J. Am. Acad. Dermatol.
2020,83, e355–e356. [CrossRef]
50.
Ismail, F.F.; Meah, N.; Trindade de Carvalho, L.; Bhoyrul, B.; Wall, D.; Sinclair, R. Safety of Oral Bicalutamide in Female Pattern
Hair Loss: A Retrospective Review of 316 Patients. J. Am. Acad. Dermatol. 2020,83, 1478–1479. [CrossRef]
51.
Cho, Y.H.; Lee, S.Y.; Jeong, D.W.; Choi, E.J.; Kim, Y.J.; Lee, J.G.; Yi, Y.H.; Cha, H.S. Effect of Pumpkin Seed Oil on Hair Growth in
Men with Androgenetic Alopecia: A Randomized, Double-Blind, Placebo-Controlled Trial. Evid. Based Complement. Alternat. Med.
2014,2014, 549721. [CrossRef]
52.
Ezekwe, N.; King, M.; Hollinger, J.C. The Use of Natural Ingredients in the Treatment of Alopecias with an Emphasis on Central
Centrifugal Cicatricial Alopecia: A Systematic Review. J. Clin. Aesthet. Dermatol. 2020,13, 23–27. [PubMed]
53.
Ibrahim, I.M.; Hasan, M.S.; Elsabaa, K.I.; Elsaie, M.L. Pumpkin Seed Oil vs. Minoxidil 5% Topical Foam for the Treatment of
Female Pattern Hair Loss: A Randomized Comparative Trial. J. Cosmet. Dermatol. 2021,20, 2867–2873. [CrossRef] [PubMed]
54.
Ufomadu, P. Complementary and Alternative Supplements: A Review of Dermatologic Effectiveness for Androgenetic Alopecia.
Bayl. Univ. Med. Cent. Proc. 2024,37, 111–117. [CrossRef] [PubMed]
55.
Mirmirani, P. Hormonal Changes in Menopause: Do They Contribute to a “midlife Hair Crisis” in Women? Br. J. Dermatol. 2011,
165 (Suppl. 3), 7–11. [CrossRef] [PubMed]
56.
Zouboulis, C.C.; Blume-Peytavi, U.; Kosmadaki, M.; Roó, E.; Vexiau-Robert, D.; Kerob, D.; Goldstein, S.R. Skin, Hair and beyond:
The Impact of Menopause. Climacteric 2022,25, 434–442. [CrossRef] [PubMed]
57. Minkin, M.J. Menopause: Hormones, Lifestyle, and Optimizing Aging. Obs. Gynecol. Clin. N. Am. 2019,46, 501–514. [CrossRef]
[PubMed]
58.
Lambrinoudaki, I.; Paschou, S.A.; Lumsden, M.A.; Faubion, S.; Makrakis, E.; Kalantaridou, S.; Panay, N. Premature Ovarian
Insufficiency: A Toolkit for the Primary Care Physician. Maturitas 2021,147, 53–63. [CrossRef]
59. Richard-Eaglin, A. Male and Female Hypogonadism. Nurs. Clin. N. Am. 2018,53, 395–405. [CrossRef]
60. Randall, V.A. Androgens and Hair Growth. Dermatol. Ther. 2008,21, 314–328. [CrossRef]
61.
Kamp, E.; Ashraf, M.; Musbahi, E.; DeGiovanni, C. Menopause, Skin and Common Dermatoses. Part 1: Hair Disorders. Clin. Exp.
Dermatol. 2022,47, 2110–2116. [CrossRef]
62. Li, R.; Shen, Y. Estrogen and Brain: Synthesis, Function and Diseases. Front. Biosci. 2005,10, 257–267. [CrossRef]
63. Price, V.H. Androgenetic Alopecia in Women. J. Investig. Dermatol. Symp. Proc. 2003,8, 24–27. [CrossRef]
Biomedicines 2024,12, 513 13 of 14
64.
Rinaldi, F.; Trink, A.; Mondadori, G.; Giuliani, G.; Pinto, D. The Menopausal Transition: Is the Hair Follicle “Going through
Menopause”? Biomedicines 2023,11, 3041. [CrossRef]
65.
Riedel-Baima, B.; Riedel, A. Female Pattern Hair Loss May Be Triggered by Low Oestrogen to Androgen Ratio. Endocr. Regul.
2008,42, 13–16.
66.
Desai, K.; Almeida, B.; Miteva, M. Understanding Hormonal Therapies: Overview for the Dermatologist Focused on Hair.
Dermatology 2021,237, 786–791. [CrossRef] [PubMed]
67.
Endo, Y.; Obayashi, Y.; Murakoshi, M.; Saito, J.; Ueki, R. Clinical and Phototrichogrammatic Evaluation of Estradiol Replacement
Therapy on Hair Growth in Postmenopausal Japanese Women with Female Pattern Hair Loss: A Pilot Study. Int. J. Womens
Dermatol. 2023,9, e109. [CrossRef]
68.
Katsura, C.; Ogunmwonyi, I.; Kankam, H.K.; Saha, S. Breast Cancer: Presentation, Investigation and Management. Br. J. Hosp.
Med. 2022,83, 1–7. [CrossRef] [PubMed]
69.
Pistilli, B.; Lohrisch, C.; Sheade, J.; Fleming, G.F. Personalizing Adjuvant Endocrine Therapy for Early-Stage Hormone Receptor-
Positive Breast Cancer. In American Society of Clinical Oncology Educational Book; ASCO: Alexandria, VA, USA, 2022; Volume 42, p.
60. [CrossRef]
70.
Rossi, A.; Caro, G.; Magri, F.; Fortuna, M.C.; Carlesimo, M. Clinical Aspect, Pathogenesis and Therapy Options of Alopecia
Induced by Hormonal Therapy for Breast Cancer. Explor. Target. Antitumor Ther. 2021,2, 490–495. [CrossRef] [PubMed]
71.
Rozner, R.N.; Freites-Martinez, A.; Shapiro, J.; Geer, E.B.; Goldfarb, S.; Lacouture, M.E. Safety of 5
α
-Reductase Inhibitors and
Spironolactone in Breast Cancer Patients Receiving Endocrine Therapies. Breast Cancer Res. Treat. 2019,174, 15–26. [CrossRef]
72.
Czech, T.; Sugihara, S.; Nishimura, Y. Characteristics of Hair Loss after COVID-19: A Systematic Scoping Review. J. Cosmet.
Dermatol. 2022,21, 3655–3662. [CrossRef]
73.
Lee, E.Y.; Nam, Y.J.; Kang, S.; Choi, E.J.; Han, I.; Kim, J.; Kim, D.H.; An, J.H.; Lee, S.; Lee, M.H.; et al. The Local Hypothalamic-
Pituitary-Adrenal Axis in Cultured Human Dermal Papilla Cells. BMC Mol. Cell Biol. 2020,21, 42. [CrossRef]
74.
Pondeljak, N.; Lugovi´c-Mihi ´c, L. Stress-Induced Interaction of Skin Immune Cells, Hormones, and Neurotransmitters. Clin. Ther.
2020,42, 757–770. [CrossRef]
75. Kalner, S.; Vergilis, I. Reversal of Stress-Associated Alopecia. J. Drugs Dermatol. 2023,22, 300–301. [CrossRef]
76.
Millington, G.W.M.; Palmer, H.E. Proopiomelanocortin (POMC) and Psychodermatology. Ski. Health Dis. 2023,3, e201. [CrossRef]
77.
Maloh, J.; Engel, T.; Natarelli, N.; Nong, Y.; Zufall, A.; Sivamani, R.K. Systematic Review of Psychological Interventions for
Quality of Life, Mental Health, and Hair Growth in Alopecia Areata and Scarring Alopecia. J. Clin. Med. 2023,12, 964. [CrossRef]
78.
Kageyama, K.; Iwasaki, Y.; Daimon, M. Hypothalamic Regulation of Corticotropin-Releasing Factor under Stress and Stress
Resilience. Int. J. Mol. Sci. 2021,22, 12242. [CrossRef]
79.
Ahn, D.; Kim, H.; Lee, B.; Hahm, D.-H. Psychological Stress-Induced Pathogenesis of Alopecia Areata: Autoimmune and
Apoptotic Pathways. Int. J. Mol. Sci. 2023,24, 11711. [CrossRef]
80.
Acharya, P.; Mathur, M.C. Oxidative Stress in Alopecia Areata: A Systematic Review and Meta-Analysis. Int. J. Dermatol. 2020,59,
434–440. [CrossRef] [PubMed]
81.
Kim, H.S.; Cho, D.H.; Kim, H.J.; Lee, J.Y.; Cho, B.K.; Park, H.J. Immunoreactivity of Corticotropin-Releasing Hormone, Adreno-
corticotropic Hormone and Alpha-Melanocyte-Stimulating Hormone in Alopecia Areata. Exp. Dermatol. 2006,15, 515–522.
[CrossRef] [PubMed]
82.
Bertolini, M.; McElwee, K.; Gilhar, A.; Bulfone-Paus, S.; Paus, R. Hair Follicle Immune Privilege and Its Collapse in Alopecia
Areata. Exp. Dermatol. 2020,29, 703–725. [CrossRef] [PubMed]
83.
Lee, S.; Pi, L.-Q.; Park, Y.-L.; Whang, K.-U.; Jeon, S.-Y.; Lee, W.-S. The Effect of Proopiomelanocortin-Derived Peptides on the
Immune System of Human Hair Follicles. J. Dermatol. Sci. 2009,55, 195–197. [CrossRef]
84.
Cuellar-Barboza, A.; Cardenas-de la Garza, J.A.; Cruz-Gómez, L.G.; Barboza-Quintana, O.; Flores-Gutiérrez, J.P.; Gómez-Flores,
M.; Welsh, O.; Ocampo-Candiani, J.; Herz-Ruelas, M.E. Local Secretion of Stress Hormones Increases in Alopecia Areata Lesions
after Treatment with UVA-1 Phototherapy. Exp. Dermatol. 2020,29, 259–264. [CrossRef] [PubMed]
85.
Fischer, T.W.; Bergmann, A.; Kruse, N.; Kleszczynski, K.; Skobowiat, C.; Slominski, A.T.; Paus, R. New Effects of Caffeine on
Corticotropin-Releasing Hormone (CRH)-Induced Stress along the Intrafollicular Classical Hypothalamic-Pituitary-Adrenal
(HPA) Axis (CRH-R1/2, IP3 -R, ACTH, MC-R2) and the Neurogenic Non-HPA Axis (Substance P, p75NTR and TrkA) in Ex Vivo
Human Male Androgenetic Scalp Hair Follicles. Br. J. Dermatol. 2021,184, 96–110. [CrossRef] [PubMed]
86.
Thom, E. Stress and the Hair Growth Cycle: Cortisol-Induced Hair Growth Disruption. J. Drugs Dermatol. 2016,15, 1001–1004.
[PubMed]
87.
Schmidt, J.B. Hormonal Basis of Male and Female Androgenic Alopecia: Clinical Relevance. Ski. Pharmacol. 1994,7, 61–66.
[CrossRef] [PubMed]
88.
El-Garf, A.; Mohie, M.; Salah, E. Trichogenic Effect of Topical Ketoconazole versus Minoxidil 2% in Female Pattern Hair Loss: A
Clinical and Trichoscopic Evaluation. Biomed. Dermatol. 2019,3, 8. [CrossRef]
89.
Fields, J.R.; Vonu, P.M.; Monir, R.L.; Schoch, J.J. Topical Ketoconazole for the Treatment of Androgenetic Alopecia: A Systematic
Review. Dermatol. Ther. 2020,33, e13202. [CrossRef]
90. Sinawe, H.; Casadesus, D. Ketoconazole. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2024.
91.
Choi, F.D.; Juhasz, M.L.W.; Atanaskova Mesinkovska, N. Topical Ketoconazole: A Systematic Review of Current Dermatological
Applications and Future Developments. J. Dermatol. Treat. 2019,30, 760–771. [CrossRef]
Biomedicines 2024,12, 513 14 of 14
92.
Marks, D.H.; Prasad, S.; De Souza, B.; Burns, L.J.; Senna, M.M. Topical Antiandrogen Therapies for Androgenetic Alopecia and
Acne Vulgaris. Am. J. Clin. Dermatol. 2020,21, 245–254. [CrossRef]
93.
Gupta, A.K.; Carviel, J.L.; Foley, K.A.; Shear, N.H.; Piraccini, B.M.; Piguet, V.; Tosti, A. Monotherapy for Alopecia Areata: A
Systematic Review and Network Meta-Analysis. Ski. Appendage Disord 2019,5, 331–337. [CrossRef]
94.
Fukumoto, T.; Fukumoto, R.; Magno, E.; Oka, M.; Nishigori, C.; Horita, N. Treatments for Alopecia Areata: A Systematic Review
and Network Meta-Analysis. Dermatol. Ther. 2021,34, e14916. [CrossRef] [PubMed]
95.
Lai, V.W.Y.; Chen, G.; Gin, D.; Sinclair, R. Systemic Treatments for Alopecia Areata: A Systematic Review. Australas J. Dermatol.
2019,60, e1–e13. [CrossRef]
96.
Barton, V.R.; Toussi, A.; Awasthi, S.; Kiuru, M. Treatment of Pediatric Alopecia Areata: A Systematic Review. J. Am. Acad.
Dermatol. 2022,86, 1318–1334. [CrossRef] [PubMed]
97.
Gallaga, N.M.; Carrillo, B.; Good, A.; Munoz-Gonzalez, A.; Ross, L. Pediatric Pulse Dose Corticosteroid Therapy Dosing and
Administration in the Treatment of Alopecia Areata: A Review of Literature. Pediatr. Dermatol. 2023,40, 276–281. [CrossRef]
98.
Cieszy´nski, Ł.; Jendrzejewski, J.; Wi´sniewski, P.; Owczarzak, A.; Sworczak, K. Hair Cortisol Concentration in a Population
without Hypothalamic-Pituitary-Adrenal Axis Disorders. Adv. Clin. Exp. Med. 2019,28, 369–373. [CrossRef] [PubMed]
99.
Nijakowski, K.; Owecki, W.; Jankowski, J.; Surdacka, A. Salivary Biomarkers for Alzheimer’s Disease: A Systematic Review with
Meta-Analysis. Int. J. Mol. Sci. 2024,25, 1168. [CrossRef]
100. Hussein, R.S.; Atia, T.; Bin Dayel, S. Impact of Thyroid Dysfunction on Hair Disorders. Cureus 2023,15, e43266. [CrossRef]
101.
van Beek, N.; Bodó, E.; Kromminga, A.; Gáspár, E.; Meyer, K.; Zmijewski, M.A.; Slominski, A.; Wenzel, B.E.; Paus, R. Thyroid
Hormones Directly Alter Human Hair Follicle Functions: Anagen Prolongation and Stimulation of Both Hair Matrix Keratinocyte
Proliferation and Hair Pigmentation. J. Clin. Endocrinol. Metab. 2008,93, 4381–4388. [CrossRef]
102.
Popa, A.; Carsote, M.; Cretoiu, D.; Dumitrascu, M.C.; Nistor, C.-E.; Sandru, F. Study of the Thyroid Profile of Patients with
Alopecia. J. Clin. Med. 2023,12, 1115. [CrossRef]
103.
Bin Dayel, S.; Hussein, R.S.; Atia, T.; Abahussein, O.; Al Yahya, R.S.; Elsayed, S.H. Is Thyroid Dysfunction a Common Cause of
Telogen Effluvium?: A Retrospective Study. Medicine 2024,103, e36803. [CrossRef]
104.
Carmona-Rodríguez, M.; Moro-Bolado, F.; Romero-Aguilera, G.; Ruiz-Villaverde, R.; Carriel, V. Frontal Fibrosing Alopecia: An
Observational Single-Center Study of 306 Cases. Life 2023,13, 1344. [CrossRef] [PubMed]
105.
Jonklaas, J.; Bianco, A.C.; Bauer, A.J.; Burman, K.D.; Cappola, A.R.; Celi, F.S.; Cooper, D.S.; Kim, B.W.; Peeters, R.P.; Rosenthal,
M.S.; et al. Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on
Thyroid Hormone Replacement. Thyroid 2014,24, 1670–1751. [CrossRef] [PubMed]
106.
Cohen, B.; Cadesky, A.; Jaggi, S. Dermatologic Manifestations of Thyroid Disease: A Literature Review. Front. Endocrinol. 2023,14,
1167890. [CrossRef]
107.
Deo, K.; Sharma, Y.K.; Wadhokar, M.; Tyagi, N. Clinicoepidemiological Observational Study of Acquired Alopecias in Females
Correlating with Anemia and Thyroid Function. Dermatol. Res. Pr. 2016,2016, 6279108. [CrossRef] [PubMed]
108.
Mazhar, M.W.; Mehmood, J.; Saif, S.; Iftikhar, H.; Khan, U.; Sikandar, M.; Manan, A.; Irfan, M.; Saleem, T.; Mumtaz, M. Thyroidism
Effect on Alopecia Patients in Pakistan. Asian J. Adv. Med. Sci. 2021,1, 302–305. [CrossRef]
109. Horesh, E.J.; Chéret, J.; Paus, R. Growth Hormone and the Human Hair Follicle. Int. J. Mol. Sci. 2021,22, 13205. [CrossRef]
110. Lurie, R.; Ben-Amitai, D.; Laron, Z. Laron Syndrome (Primary Growth Hormone Insensitivity): A Unique Model to Explore the
Effect of Insulin-like Growth Factor 1 Deficiency on Human Hair. Dermatology 2004,208, 314–318. [CrossRef]
111.
Kanaka-Gantenbein, C.; Kogia, C.; Abdel-Naser, M.B.; Chrousos, G.P. Skin Manifestations of Growth Hormone-Induced Diseases.
Rev. Endocr. Metab. Disord 2016,17, 259–267. [CrossRef]
112.
Yamada, S.; Fukuhara, N.; Nishioka, H.; Yamaguchi-Okada, M.; Takeshita, A.; Takeuchi, Y. Scalp Hair Loss after Transsphenoidal
Adenomectomy in Patients with Acromegaly. Clin. Endocrinol. 2013,79, 386–393. [CrossRef]
113.
Aguiar-Oliveira, M.H.; Salvatori, R. Disruption of the GHRH Receptor and Its Impact on Children and Adults: The Itabaianinha
Syndrome. Rev. Endocr. Metab. Disord 2021,22, 81–89. [CrossRef]
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