Vitamin D
PTHrP
Estrogens
Androgens
T3
MSH
ACTH
TRH
GH
The skin cells contain the entire biochemical apparatus necessary for production of glucocorticoids, androgens, and estrogens either from precursors of systemic origin or, alternatively, through the conversion of cholesterol to pregnenolone and its subsequent transformation to biologically active steroids. The level of production and nature of the final steroid products are dependent on the cell type or cutaneous compartment, e.g., epidermis, dermis, adnexal structures, or adipose tissue [41].
The skin can transform the steroids dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) into active androgens and estrogens. Specifically, enzymatic activity corresponding to 3b-hydroxysteroid dehydrogenase/D5–D4 isomerase (3b-HSD) has been localized to the sebaceous glands and, to a lesser degree, in hair follicles, epidermis, and eccrine glands, while 17b-hydroxysteroid dehydrogenase (17b-HSD) has been localized to follicular and epidermal keratinocytes. 3b-HSD converts DHEA into 4-androstenedione and 5-androstene-3b,17b-diol into testosterone, while 17b-HSD converts DHEA into 5-androstene- 3b,17b-diol, 4-androstenedione into testosterone, and androstenedione into DHT. Testosterone is also converted into DHT through the action of a 5a-reductase, detected in dermal and dermal papilla fibroblasts, follicular and epidermal keratinocytes, and sebaceous and apocrine glands. There are two isozymic forms of the 5a-reductase, but the skin expresses predominantly the type I in a highly specific cellular and regional distribution. Nevertheless, cutaneous expression of 5a-reductase type 2 has been also reported, but at much lower levels; this form has been immunodetected in hair follicles of the human scalp. The skin immune system can also convert DHEA into 5-androstene-3b,17b-diol and into 5-androstene-3b,7b,17b-triol. Cutaneous conversion of testosterone into estradiol is mediated by an aromatase expressed in dermal fibroblasts and adipocytes, but not in keratinocytes. However, in keratinocytes 17b-HSD can transform 17b-estradiol into estrone or estrone into 17bestradiol [41].
Locally produced glucocorticoids, androgens, and estrogens affect functions of the epidermis and adnexal structures as well as local immune activity. Malfunction of these steroidogenic activities can lead to inflammatory disorders or autoimmune diseases.
3.11 Skin Disorders in Menopause
Skin conditions that tend to occur more commonly in postmenopausal women include atrophic vulvovaginitis, lichen sclerosis, dysesthetic vulvodynia, and keratoderma climactericum [42].
3.11.1 Atrophic Vulvovaginitis
Hypoestrogenism leads to atrophy of the vagina and vulval vestibule. This thinned tissue is easily irritated and is also susceptible to secondary infection. The patient complains of vulvar burning, dysuria, pruritus, tenderness, and dyspareunia. Atrophy reverses rapidly and returns to premenopausal levels after 1–2 weeks of estrogen therapy [43].
3.11.2 Lichen Sclerosis
Lichen sclerosus is a rare inflammatory disease of unknown etiology. It mainly affects postmenopausal women in the anogenital area and only in 2.5 % cases it is found exclusively at an extragenital site. The inner thighs, submammary region, and upper arms are the most commonly affected sites [44]. Topical corticosteroids, such as betamethasone dipropionate or clobetasol propionate, are effective in improving symptoms and reversing the disease process [45].
3.11.3 Dysesthetic Vulvodynia
Patients present with chronic constant unremitting vulval burning that does not respond to topical applications and frequently have no abnormality detected on physical examination. The etiology of this condition is thought to be neurological. It may be related to abnormal cutaneous perception, either centrally or at nerve root level. The pain can be bilateral, may involve the inner thighs, and may be provoked by vaginal penetration [46]. Tricyclic antidepressants such as amitriptyline and nortriptyline, in low doses, as well as some anticonvulsants, such as carbamazepine and sodium valproate, are effective for the management of neuropathic pain. These drugs should be commenced at the lowest possible dose [47].
3.11.4 Keratoderma Climactericum
Keratoderma climactericum is a hyperkeratosis of the palms and soles affecting mainly obese women. Thickening first develops in weight-bearing areas such as plantar pressure points, making walking difficult. Patients also complain of painful fissures and itch. Involvement of the hands is often discrete [42]. Treatment with a low dose of etretinate has been demonstrated to lead effectively to partial or total remission of hyperkeratosis [48].
3.12 Melanoma and Nonmelanoma Skin Cancers
Preclinical and clinical findings suggest that estrogen may be involved in the development of skin cancer. Several studies have found an association between oral contraceptive use and an increased risk of nonmelanoma skin cancer [49, 50]. However, epidemiological studies of menopausal hormone therapy and the risk of melanoma have produced mixed findings; several studies reported that hormone use was associated with increased risk of melanoma [51–53]. In the recent large multiethnic Women’s Health Initiative (WHI) clinical trials of estrogen plus progestin (E + P) vs. placebo and estrogen alone (E-alone) vs. placebo, the hormone therapy during 6 years did not affect overall incidence of nonmelanoma skin cancer or melanoma. The rates of incident nonmelanoma skin cancer and melanoma were similar between the active hormone (combined analysis of E + P and E-alone) and placebo groups (nonmelanoma skin cancer: HR = 0.98, 95 % CI = 0.89–1.07; melanoma: HR = 0.92, 95 % CI = 0.61–1.37) [54]. However, it cannot rule out a delayed effect of hormone therapy on risk of skin cancer.
3.13 Quality of Life
A variety of cutaneous changes with the menopause cause significant anxiety and may impact the quality of life. Estrogens can improve the changes in skin, and general lifestyle changes can be effective in reducing, in the long term, the signs of skin aging. The latter include the use of sun protection and over-the-counter moisturizers [55]. In addition, cosmetic interventions such as topical retinoids, facial peels, botulinum neurotoxin, soft tissue fillers, and surgical procedures can be employed to improve the appearance of the skin [56, 57].
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Related posts:
Effects of Hormone Replacement Therapy on Skin Viscoelasticity During Climacteric Aging
Atrophic Vaginitis in the Menopause
Sensory Perception on the Vulva and Extragenital Sites
Physical Activity and Quality of Life During Menopausal Transition and Postmenopause
Changes to Skin with Aging and the Effects of Menopause and Incontinence
Skin and Menopause
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