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CHAPTER 5 HORMONES AND AGING SKIN
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TABLE 5-3 Menopause, Andropause, and Adrenopause These Age-Related Conditions are Characterized by a Decline in the Hormones Listed CONDITION Menopause Adrenopause Andropause HORMONE THAT DECREASES Estrogen (Estradiol) DHEA/DHEAS Androgens
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ESTROGEN AND ANDROGEN RECEPTORS IN THE SKIN
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All steroid hormones, such as estradiol and testosterone, exert their biologic action by binding to nuclear receptors, thereby initiating transcription and translation of proteins While the classic estrogen receptor (ER- ) was discovered in the 1970s, ER- was discovered and isolated from human tissue in 19969 Since then, studies have shown that ER- is the predominant estrogen receptor in human skin and highly expressed in the epidermis, blood vessels, dermal fibroblasts, and outer root sheath of the hair follicle (the location of the bulge and stem cells) ER- and the androgen receptor (which can bind testosterone or DHT) are expressed only in dermal papilla cells of the hair follicle10,11 All three receptors are also found in sebaceous glands10,11 In eccrine sweat glands, ER- is highly expressed as are, to a lesser extent, androgen and progesterone receptors11 Recent studies of human adipose tissue found that sex hormone receptors differ by site, with ER- being highly expressed in subcutaneous tissue12 With all these recent findings, it is clear that sex hormones are involved in the proliferation, differentiation, and function of the skin, adnexal structures, as well as fat, and that this regulation is far more intricate than previously thought In addition, the recent description of the ER- receptor (ER1 5) isoforms has made this subject more complex12
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SEX HORMONES AND ACNE
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Both estrogen and androgen receptors are expressed in sebaceous glands,10,11 and both hormones are known to have an effect on these structures During puberty, the increase of androgenetic hormones triggers sebaceous gland growth with increased release of sebum This sebum is a source of nutrition for skin bacteria such as Propionibacterium acnes Proliferation of these bacteria leads to greater production of inflammatory factors, causing inflammation and pustule formation clinically seen as acne Estrogens, however, demonstrate antiinflammatory properties by decreasing neutrophil chemotaxis,13 thereby counteracting the inflammatory effects of P acnes In contrast, androgens prolong inflammation,14 and therefore compound their negative effects, resulting in worsened acne This may help to explain why so many young women with acne benefit from the particular
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hormonal combinations found in oral contraceptives These agents are especially useful for patients with the triad of acne, hirsutism, and abnormal menstrual periods In fact, some oral contraceptives such as Ortho TriCyclen and Yaz have received FDA approval for use in the treatment of acne These oral contraceptives can relieve the symptoms of acne by reducing the amount of circulating androgens They also stimulate the production of sex hormone-binding globulin, thus reducing free and biologically active testosterone derived from both the ovaries and adrenal glands At the same time, they suppress the ovarian production of testosterone by direct gonadotropin suppression Hormones also play a role in adult female acne As women approach menopause and their estrogen levels decrease, the actions of androgens are unmasked Testosterone stimulates the sebaceous glands to produce sebum, as is seen in puberty, leading to an increase in acne Many female patients are surprised to find themselves with acne well into adulthood Current studies demonstrate that androgen levels in patients with acne are higher than those in controls, and the fact that people with androgen insensitivity syndrome do not develop acne also points to androgens as the main culprit in this condition15 Local factors, other than androgen plasma levels, contribute to androgen levels in the skin and thus the development of acne Since the skin contains enzymes such as aromatase, it can convert precursor hormones into more potent androgens such as testosterone and DHT at the cellular level For a more extensive discussion on acne, (see 15)
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