madman
Super Moderator
Abstract
Hormones have an intimate relationship with hair growth. Hormonal replacement therapy is used to treat menopausal symptoms and to provide protection from chronic diseases for which postmenopausal women may be at risk. Additionally, hormonal therapies are prescribed for contraception and treatment of acne. Considering the widespread use of such therapies, there is a demand for further understanding of their implications in hair disorders. This article reviews the specific properties of current estrogen- and progesterone containing hormonal treatments and their implications for the patient with hair loss. The complexity of the task comes from the paucity of data and discrepancy in the literature on the effect of the specific hormonal-receptor activities.
Introduction
Hormonal therapies containing estrogen and/or progestogens are frequently used in women for menopausal symptoms, contraception, and acne. A common scenario in the trichology clinics is a female patient with telogen effluvium or androgenetic alopecia on a birth control therapy or hormonal replacement therapy (HRT) asking if they can safely continue the hormonal therapy or they need to switch or discontinue it since they are highly concerned about the progression of hair loss. Hormones have an intimate relationship with hair growth [1]. The objective of this review is to make dermatologists and particularly trichologists familiar with the specific properties of current estrogen- and progesterone-containing hormonal treatments and their implications for the patient with hair loss.
Main Findings
Basic Terminology
Hormonal activity is the modulation of a specific receptor by effector molecules. The binding of steroid hormones (including progesterone, androgens, estrogens, glucocorticoids, and mineralocorticoids) to their receptors induces a conformational change in the receptors, which subsequently serve as transcription factors and regulate gene expression [2–4].
Progestational activity refers to the induction of a secretory endometrium to support gestation [5]. Progesterone receptors are additionally present in the mammary gland, brain, pituitary gland, and immune cells [5]. The term “progestogen” refers to compounds with progestational activity [5].
Androgenic and estrogenic activities involve the development and maintenance of male and female sexual characteristics, respectively. Estrogen has important uterotropic effects and induces a specific growth pattern of the endometrium. In scientific studies, the weight of reproductive organs (prostate/seminal vesicles for males and uterus for females) has been used to measure estrogenic and androgenic activity [2]. Androgen receptor (AR) and estrogen receptors (ER) are also expressed in many other tissues including muscle, bone, gastrointestinal tract, and skin [2, 5, 6]. Moreover, two principal isoforms of ER (ER-α and ER-β) have distinct, tissue-dependent expression and functions [5, 6]. Thus, androgens/estrogens can have diverse and nuanced effects, unrelated to virilization and feminization.
Glucocorticoid activity refers to a variety of functions, ranging from metabolism to inflammation. Glucocorticoid receptors (GR) are ubiquitously expressed, with particular prominence in immune-function cells [3, 5].
Mineralocorticoid activity refers to maintaining fluid and electrolyte balance [5]. Mineralocorticoid receptors (MR) are present in many tissues, including throughout the cardiovascular system, kidney, central nervous system, and adipocytes [5].
*Estrogen- and Progesterone-Containing Therapies
*Estrogens
*Progestogens
*Pharmacodynamics of Combined Estrogen and Progestogen Therapies
*Bioidentical Hormone Therapy
Hormones and Hair
Androgens are principal regulators of normal human hair growth [21, 22].Sebaceous glands, hair follicles, and many types of skin cells express AR and the enzyme 5α-reductase, which converts testosterone to its more potent form, DHT [2, 21, 23]. The dermal papilla in the center of the hair bulb is a principal site of androgen action and influences keratinocytes of the hair follicle through paracrine signaling, regulating the size, shape, and color of the hair as well as its frequency of regeneration [21, 24–26]. Androgenic or antiandrogenic activity results in loss or growth of scalp hair, respectively [2, 22, 27]. However, follicle response to androgens is variable [2, 25]. Increased levels of DHT can lead to androgenetic alopecia in the scalp but promote male-type hair growth in other parts of the body [1, 2]. Additionally, hormones are postulated to play a central role in the progression of the hair cycle; for example, DHT is thought to shorten the anagen phase [28, 29]. The precise mechanisms of hormonal modulation of the hair cycle remain to be elucidated.
Certain polymorphisms of the androgen receptor gene are thought to facilitate ease of activation of the receptor, thus providing a genetic predisposition for androgen-related disorders. These polymorphisms have been demonstrated to be more prevalent in patients with androgenetic alopecia as well as acne and hirsutism [21].
The role of estrogens in hair growth is controversial and complex [6, 20, 24]. The increase in female pattern hair loss (FPHL) following menopause suggests that estrogen promotes hair growth, although high-quality data have not yet become available to confirm an association between hair loss and menopausal status [30]. Studies in ovariectomized mice, serving to model postmenopausal FPHL, have demonstrated that a decrease in estrogen results in hair loss [31]. Estrogen has been postulated to aid hair growth by extending the anagen phase of the hair growth cycle [32], during pregnancy, for example [6]. In the postpartum period, an increase in the number of hairs in the telogen phase results in increased hair shedding [5, 6, 24]. Estrogen is presumed to be the principal hormone responsible for changes in hair cycling around pregnancy; however, the interference by other hormones (such as prolactin) cannot be excluded.
The differential expression and function of the two isoforms of ER, ER-α and ER-β, may also be relevant to the effect of estrogen on hair growth. Studies have demonstrated that ER-β is more strongly expressed than ER-α in anagen hair follicles of the nonbalding scalp [33], and FPHL has been linked to polymorphisms of the ER-β gene [6, 34].
In addition to their independent modulation of hair growth, estrogens are thought to treat androgen-dependent disorders by indirectly interfering with androgen action: for example, by increasing SHBG levels and reducing androgen availability [24].
*Implications of Hormone Therapies in Hair Loss
*Hormone-Modulating Therapies: SERMs and Aromatase Inhibitors
Conclusion and Authors’ Clinical Approach
While the role of androgens is commonly encountered in the study of hair biology, the consequences of commonly prescribed therapies with androgenic properties, as in HRT and COCs, have not been systemically studied, and data are lacking.
Based on the pharmacological properties of these drugs and the current knowledge regarding the pathophysiology of alopecia conditions, we tend to avoid therapies with net androgenic properties in patients with hair loss. Micronized progesterone is the main component of most HRTs and based on its largely antiandrogenic effect, it is acceptable to be used in women with hair loss. On the other hand, some progestins may be beneficial in treating alopecic disorders based on their antiandrogenic activity and inhibition of 5α-reductase (such as chlormadinone acetate, drospirenone, cyproterone acetate, and dienogest). For patients seeking contraception who cannot tolerate the estrogen component in COCs, nonhormonal modalities (such as the copper IUD) or less androgenic progestins (such as the etonogestrel implant) should be considered. We also recommend close work with the gynecologists in order to provide individually tailored, safe, and satisfactory hormonal contraception or hormonal replacement.
For breast cancer patients who experience alopecia attributed to SERMs or aromatase inhibitors, the authors’ approach is to add topical/oral minoxidil or other nonhormonal modalities to mitigate hair loss while maintaining the endocrine therapy.
In conclusion, there remains the critical need for hormonal therapies to be properly evaluated for effects on hair growth/loss before their implementation in clinical practice.
Hormones have an intimate relationship with hair growth. Hormonal replacement therapy is used to treat menopausal symptoms and to provide protection from chronic diseases for which postmenopausal women may be at risk. Additionally, hormonal therapies are prescribed for contraception and treatment of acne. Considering the widespread use of such therapies, there is a demand for further understanding of their implications in hair disorders. This article reviews the specific properties of current estrogen- and progesterone containing hormonal treatments and their implications for the patient with hair loss. The complexity of the task comes from the paucity of data and discrepancy in the literature on the effect of the specific hormonal-receptor activities.
Introduction
Hormonal therapies containing estrogen and/or progestogens are frequently used in women for menopausal symptoms, contraception, and acne. A common scenario in the trichology clinics is a female patient with telogen effluvium or androgenetic alopecia on a birth control therapy or hormonal replacement therapy (HRT) asking if they can safely continue the hormonal therapy or they need to switch or discontinue it since they are highly concerned about the progression of hair loss. Hormones have an intimate relationship with hair growth [1]. The objective of this review is to make dermatologists and particularly trichologists familiar with the specific properties of current estrogen- and progesterone-containing hormonal treatments and their implications for the patient with hair loss.
Main Findings
Basic Terminology
Hormonal activity is the modulation of a specific receptor by effector molecules. The binding of steroid hormones (including progesterone, androgens, estrogens, glucocorticoids, and mineralocorticoids) to their receptors induces a conformational change in the receptors, which subsequently serve as transcription factors and regulate gene expression [2–4].
Progestational activity refers to the induction of a secretory endometrium to support gestation [5]. Progesterone receptors are additionally present in the mammary gland, brain, pituitary gland, and immune cells [5]. The term “progestogen” refers to compounds with progestational activity [5].
Androgenic and estrogenic activities involve the development and maintenance of male and female sexual characteristics, respectively. Estrogen has important uterotropic effects and induces a specific growth pattern of the endometrium. In scientific studies, the weight of reproductive organs (prostate/seminal vesicles for males and uterus for females) has been used to measure estrogenic and androgenic activity [2]. Androgen receptor (AR) and estrogen receptors (ER) are also expressed in many other tissues including muscle, bone, gastrointestinal tract, and skin [2, 5, 6]. Moreover, two principal isoforms of ER (ER-α and ER-β) have distinct, tissue-dependent expression and functions [5, 6]. Thus, androgens/estrogens can have diverse and nuanced effects, unrelated to virilization and feminization.
Glucocorticoid activity refers to a variety of functions, ranging from metabolism to inflammation. Glucocorticoid receptors (GR) are ubiquitously expressed, with particular prominence in immune-function cells [3, 5].
Mineralocorticoid activity refers to maintaining fluid and electrolyte balance [5]. Mineralocorticoid receptors (MR) are present in many tissues, including throughout the cardiovascular system, kidney, central nervous system, and adipocytes [5].
*Estrogen- and Progesterone-Containing Therapies
*Estrogens
*Progestogens
*Pharmacodynamics of Combined Estrogen and Progestogen Therapies
*Bioidentical Hormone Therapy
Hormones and Hair
Androgens are principal regulators of normal human hair growth [21, 22].Sebaceous glands, hair follicles, and many types of skin cells express AR and the enzyme 5α-reductase, which converts testosterone to its more potent form, DHT [2, 21, 23]. The dermal papilla in the center of the hair bulb is a principal site of androgen action and influences keratinocytes of the hair follicle through paracrine signaling, regulating the size, shape, and color of the hair as well as its frequency of regeneration [21, 24–26]. Androgenic or antiandrogenic activity results in loss or growth of scalp hair, respectively [2, 22, 27]. However, follicle response to androgens is variable [2, 25]. Increased levels of DHT can lead to androgenetic alopecia in the scalp but promote male-type hair growth in other parts of the body [1, 2]. Additionally, hormones are postulated to play a central role in the progression of the hair cycle; for example, DHT is thought to shorten the anagen phase [28, 29]. The precise mechanisms of hormonal modulation of the hair cycle remain to be elucidated.
Certain polymorphisms of the androgen receptor gene are thought to facilitate ease of activation of the receptor, thus providing a genetic predisposition for androgen-related disorders. These polymorphisms have been demonstrated to be more prevalent in patients with androgenetic alopecia as well as acne and hirsutism [21].
The role of estrogens in hair growth is controversial and complex [6, 20, 24]. The increase in female pattern hair loss (FPHL) following menopause suggests that estrogen promotes hair growth, although high-quality data have not yet become available to confirm an association between hair loss and menopausal status [30]. Studies in ovariectomized mice, serving to model postmenopausal FPHL, have demonstrated that a decrease in estrogen results in hair loss [31]. Estrogen has been postulated to aid hair growth by extending the anagen phase of the hair growth cycle [32], during pregnancy, for example [6]. In the postpartum period, an increase in the number of hairs in the telogen phase results in increased hair shedding [5, 6, 24]. Estrogen is presumed to be the principal hormone responsible for changes in hair cycling around pregnancy; however, the interference by other hormones (such as prolactin) cannot be excluded.
The differential expression and function of the two isoforms of ER, ER-α and ER-β, may also be relevant to the effect of estrogen on hair growth. Studies have demonstrated that ER-β is more strongly expressed than ER-α in anagen hair follicles of the nonbalding scalp [33], and FPHL has been linked to polymorphisms of the ER-β gene [6, 34].
In addition to their independent modulation of hair growth, estrogens are thought to treat androgen-dependent disorders by indirectly interfering with androgen action: for example, by increasing SHBG levels and reducing androgen availability [24].
*Implications of Hormone Therapies in Hair Loss
*Hormone-Modulating Therapies: SERMs and Aromatase Inhibitors
Conclusion and Authors’ Clinical Approach
While the role of androgens is commonly encountered in the study of hair biology, the consequences of commonly prescribed therapies with androgenic properties, as in HRT and COCs, have not been systemically studied, and data are lacking.
Based on the pharmacological properties of these drugs and the current knowledge regarding the pathophysiology of alopecia conditions, we tend to avoid therapies with net androgenic properties in patients with hair loss. Micronized progesterone is the main component of most HRTs and based on its largely antiandrogenic effect, it is acceptable to be used in women with hair loss. On the other hand, some progestins may be beneficial in treating alopecic disorders based on their antiandrogenic activity and inhibition of 5α-reductase (such as chlormadinone acetate, drospirenone, cyproterone acetate, and dienogest). For patients seeking contraception who cannot tolerate the estrogen component in COCs, nonhormonal modalities (such as the copper IUD) or less androgenic progestins (such as the etonogestrel implant) should be considered. We also recommend close work with the gynecologists in order to provide individually tailored, safe, and satisfactory hormonal contraception or hormonal replacement.
For breast cancer patients who experience alopecia attributed to SERMs or aromatase inhibitors, the authors’ approach is to add topical/oral minoxidil or other nonhormonal modalities to mitigate hair loss while maintaining the endocrine therapy.
In conclusion, there remains the critical need for hormonal therapies to be properly evaluated for effects on hair growth/loss before their implementation in clinical practice.
