ArticleLiterature Review

Acne: Hormonal concepts and therapy

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Abstract

Acne vulgaris is the most common skin condition observed in the medical community. Although we know that hormones are important in the development of acne, many questions remain unanswered regarding the mechanisms by which hormones exert their effects. Androgens such as dihydrotestosterone (DHT) and testosterone, the adrenal precursor dehydroepiandrosterone sulfate (DHEAS), estrogens such as estradiol, and other hormones, including growth hormone and insulin-like growth factors (IGFs), may be important in acne. It is not known whether these hormones are taken up from the serum by the sebaceous gland, whether they are produced locally within the gland, or whether a combination of these processes is involved. Finally, the cellular and molecular mechanisms by which these hormones exert their influence on the sebaceous gland have not been fully elucidated. Hormonal therapy is an option in women with acne not responding to conventional treatment or with signs of endocrine abnormalities.

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... Sex hormones and metabolic hormones seem to play a role in the development and severity of acne. For example, elevated dehydroepiandrosterone (DHEAS), dihydrotestosterone (DHT), and insulin-like growth factor 1 (IGF-1) positively correlate with increasing acne lesion counts in women and androstenedione and DHEAS in men. 2 The various hormones possibly implicated in acne and their proposed mechanisms are summarised below: 3 • Androgens (testosterone, DHT, DHEAS) increase the size and secretion of sebaceous glands. Sources of circulating androgens include the adrenal glands, ovaries, or testes. ...
... mg may be administered every day or every other day, at bedtime. 3 Adrenal suppression is possible, especially if dexamethasone is used, and can be screened with ACTH stimulation test, two to three months after starting therapy. 3,30 Duration of therapy is limited by the long-term side-effect of osteoporosis, and should therefore be limited to six months. ...
... mg may be administered every day or every other day, at bedtime. 3 Adrenal suppression is possible, especially if dexamethasone is used, and can be screened with ACTH stimulation test, two to three months after starting therapy. 3,30 Duration of therapy is limited by the long-term side-effect of osteoporosis, and should therefore be limited to six months. 30 ...
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Acne and its management
... for female patients with acne, hirsutism and alopecia for years [30]. In doses of 50 to 100 mg once or twice daily, taken with meals, it has been shown to reduce sebum excretion rate by 30% to 50% and improve acne [17,31,32]. Clinical improvement of acne is generally seen after 3 months and effective maintenance doses range from 25 to 50 mg daily. ...
... The potential for it to induce oestrogen dependent malignancies remains a controversial topic [35]. Treatment with spironolactone during pregnancy is contraindicated (FDA pregnancy category C) and may lead to abnormalities of the male fetal genitalia, such as hypospadias [32]. ...
... Flutamide also enhances androgens breakdown to inactive metabolites. Flutamide can be effective for the treatment of acne, hirsutism and alopecia [32]. It can be used alone or in combination with metformin or COC in patients with PCOS. ...
... Both clinical and experimental evidence support the role of androgens in stimulating sebum production: (i) the presence of acne in the prepubertal period correlates with serum levels of dehydroepiandrosterone sulfate (DHEAS), an adrenal precursor for synthesis of testosterone (3,4), (ii) subjects who lack functional androgen receptors do not produce sebum, and consequently do not develop acne (3), (iii) tumors of the ovary or the adrenal gland that are androgen producing are often associated with the development of acne (3), (iv) systemic administration of testosterone and DHEAS increases the size of the sebaceous glands and stimulates sebum production (3,5), (v) severe acne is jcbmr.com often associated with conditions of hyperandrogenism and increased sebum production (2,3,5). ...
... Both clinical and experimental evidence support the role of androgens in stimulating sebum production: (i) the presence of acne in the prepubertal period correlates with serum levels of dehydroepiandrosterone sulfate (DHEAS), an adrenal precursor for synthesis of testosterone (3,4), (ii) subjects who lack functional androgen receptors do not produce sebum, and consequently do not develop acne (3), (iii) tumors of the ovary or the adrenal gland that are androgen producing are often associated with the development of acne (3), (iv) systemic administration of testosterone and DHEAS increases the size of the sebaceous glands and stimulates sebum production (3,5), (v) severe acne is jcbmr.com often associated with conditions of hyperandrogenism and increased sebum production (2,3,5). ...
... Both clinical and experimental evidence support the role of androgens in stimulating sebum production: (i) the presence of acne in the prepubertal period correlates with serum levels of dehydroepiandrosterone sulfate (DHEAS), an adrenal precursor for synthesis of testosterone (3,4), (ii) subjects who lack functional androgen receptors do not produce sebum, and consequently do not develop acne (3), (iii) tumors of the ovary or the adrenal gland that are androgen producing are often associated with the development of acne (3), (iv) systemic administration of testosterone and DHEAS increases the size of the sebaceous glands and stimulates sebum production (3,5), (v) severe acne is jcbmr.com often associated with conditions of hyperandrogenism and increased sebum production (2,3,5). It has also been suggested that hormones affect hyperkeratinization of the sebaceous follicles (5). ...
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The pathogenesis of acne vulgaris has only been partially elucidated. Various hormones, especially androgens, are likely to play a role, but results of studies are still inconclusive. The objective of the current study was to investigate whether day to day variation in salivary testosterone correlates with acne in males. Saliva samples were collected for 120 consecutive days from each of the 40 males. Salivary testosterone concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Facial acne lesions were assessed on a daily basis by photography by the participating males. Potential confounders’ (sexual intercourse, masturbation, physical exercise and disease) were also registered every day by the participants. A significant but weak association between salivary testosterone and acne was found (n = 4602, r = 0.031, P = 0.034). Elevated testosterone concentrations were associated with an increase in acne, but when testosterone concentrations were above twice the individual average, acne lesions paradoxically decreased. The current results indicate that daily fluctuations in salivary testosterone levels in males are associated with acne patterns, but the weak correlation suggests that the effect is too small to be of clinical significance. The analysis in the current study was complicated by a large number of days on which the participants had no acne, as well as the seemingly non-monotonic relation between testosterone and acne. This may indicate that the actual relation is stronger than concluded here.
... Estratégias para Limitar a Resistência Antibiótica veis de 5 a 50 mg/dia, durante 15 dias do ciclo menstrual, quando há evidência de hiperandrogenismo. Pode re- correr-se a outros fármacos anti-androgénicos como a espironolactona (50-200 mg/dia) ou a flutamida (125 a 250 mg/dia); estes 2 últimos obrigam a controlo labo- ratorial regular, dada a hipercaliémia habitual na tera- pêutica prolongada com espironolactona e ao risco de insuficiência hepática grave com a flutamida25.3. Em casos muito específicos, como doentes com défice da 21-hidroxilase e hiperactividade supra- renal, podem ser benéficos corticosteróides em dose baixa25. ...
... Pode re- correr-se a outros fármacos anti-androgénicos como a espironolactona (50-200 mg/dia) ou a flutamida (125 a 250 mg/dia); estes 2 últimos obrigam a controlo labo- ratorial regular, dada a hipercaliémia habitual na tera- pêutica prolongada com espironolactona e ao risco de insuficiência hepática grave com a flutamida25.3. Em casos muito específicos, como doentes com défice da 21-hidroxilase e hiperactividade supra- renal, podem ser benéficos corticosteróides em dose baixa25. As principais indicações para um tratamento hor- monal na acne são 24 (Quadro V):• Mulheres com agravamento pré-menstrual;• Mulheres com acne na idade adulta, envolvendo pre- ferencialmente a metade inferior da face e pescoço; • Mulheres em qualquer idade com acne associada a seborreia, hirsutismo e irregularidades do ciclo menstrual, com ou sem hiperandrogenismo; • Jovens sexualmente activas com acne inflamatória. ...
... There are three types of ethinyl estradiol available: ethinyl estradiol-norgestimate, ethinyl estradrospirenone, and norethindrone acetate (33) . Lowandrogen progesterone was introduced to minimize the risk of malignancies linked to estrogen (34) . They are naturally antiandrogenic in their effects. ...
... Novel systemic agents in the management of acne: 1. Oral zinc: Oral zinc supplementation has been shown in several trials to reduce the number of acne lesions. It also heals lesions and reduces inflammation (34) . ...
... These factors may stimulate the production of oil, leading to an increased acne risk [2]. Puberty-related hormonal acne typically subsides, improving more or less as you reach puberty [13]. There are claims that there are certain risk factors for developing acne, including a diet rich in sugars and carbohydrates, or evolution, daily changes triggered by puberty or pregnancy, certain birth control pills or corticosteroids [13]. ...
... Puberty-related hormonal acne typically subsides, improving more or less as you reach puberty [13]. There are claims that there are certain risk factors for developing acne, including a diet rich in sugars and carbohydrates, or evolution, daily changes triggered by puberty or pregnancy, certain birth control pills or corticosteroids [13]. Men's skin is different than women's coats. ...
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What is acne vulgaris? A commonly diagnosed skin disease concerning clogging and inflammation of pilosebaceous units is called acne vulgaris. Mostly, adolescence and puberty are affected because of hormone and their daily routine. Gender is one of the critical factors to cause acne. Thus, excellent skin cares are needed to prevent acne vulgaris, leading to another symptom, including stress, low self-esteem, and depression. Importantly, due to our surroundings, there are many kinds of pollution that we have to face in our daily lives and cannot be avoided. One of the causes of acne is air pollution; air pollution can come in many kinds, such as UV rays, smoke, or PM (particulate matter). PM carries out small particles in the air that clog our skin's pores or UV rays that directly damage our face if we do not have proper protection, resulting in acne outbreaks. Treating these acne outbreaks can be a lengthy and challenging process. Therefore, this review was to provide and update the method to shield and resolving the fair facial skin among air pollution surrounding. The author conducted this review thought collecting the article from Google Scholar and Pubmed using these keywords, including Acne vulgaris, air pollution, treatment, adolescence, self-esteem, and protection. There are a few steps that will protect and help resolve your skin from air pollution. First of all, cleansing your skin with a gentle cleanser is an excellent option to keep natural moisture in your skin. After cleansing, it is essential to use a gentle and soothing toner that helps remove grease and traces of dirt from blocking your pores, which might trigger acne. Scrubbing is the next step after the toner has been applied; mild scrubbing will ensure your skin is thoroughly cleansed of all harmful particles clogging your pores. Facial oil proves to boost moisten and shield your facial skin from toxic air substances. However, for long-term using facial oil can cause irritation to your skin, another option can be moisturizer instead. Make sure to apply sunscreen to protect against both UVB and UVA rays and apply it multiple times throughout the day when you are exposed to the air pollution. In addition, high sugary, salty and fats diets have the relationship with acne vulgaris. People with acne must avoid these types of food to reduce negative effect to acne. The protection and maintenance of facial skin is significantly important to make our face healthy. Moreover, the perks of having clear and healthy facial skin can boost up your confidence as well as decreasing our stress and anxiety that are being released throughout your body.
... Androgens can also induce follicular hyperkeratosis, a key element in the pathogenesis of acne, independent of their impact on the sebaceous gland. In addition, the combination of increased sebum production and follicular hyperkeratosis enables the growth of Propionibacterium acnes bacteria that contribute to the activity of acne [4,5]. ...
... Biologically, it is hypothesized that acne and menstrual symptoms may share the same underlying pathogenetic process since elevated androgen levels, on the one hand, result in excessive sebum production and follicular hyperkeratosis that cause acne and, on the other hand, disturb the ovulatory hormones ending with premenstrual and menstrual symptoms [4][5][6][7]. However, a large crosssectional twin study conducted on 400 cases of acne twins and 2414 non-affected controls showed no association between acne and reproductive hormones [15]. ...
Article
Background Acne and menstrual symptoms are highly prevalent among young women. Since both acne and menstrual symptoms have similar hormonal pathogenesis, it is highly suggested that the two conditions are associated. Herein, we conducted this study to assess the relationship between acne and menstrual symptoms among young women. Subjects and methods In this population-based cross-sectional study, a multi-stage random sampling approach was used to include 3065 young women (18–25 years) from Egypt. Women were interviewed for their socio-demographic characteristics, gynecological history, premenstrual and menstrual symptoms, and history of acne and perimenstrual acne flare during the past 6 months. Results The mean age of women was 21.5 ± 2.2 and their age of menarche was 13.1 ± 1.5 years. During the previous 6 months, 44.8% of participants had acne. After adjusting for socio-demographic and gynecological characteristics, acne was associated with most menstrual symptoms with odds ratios (ORs) and 95% confidence intervals (CIs) as follows: [premenstrual symptoms: 1.23 (1.05–1.44) for irritation or nervousness, 1.45 (1.24–1.68) for fatigue, 1.37 (1.15–1.62) for breast tenderness, 1.48 (1.21–1.80) for abdominal bloating, and 1.36 (1.11–1.66) for nausea or vomiting], [menstrual symptoms: 1.63 (1.19–2.23) for dysmenorrhea and 1.24 (1.06–1.45) for dysmenorrhea requiring drugs], and [symptoms severity: 1.44 (1.24–1.68) for missing events and 1.38 (1.16–1.64) for medical consultation]. Of acne patients, 56.7% reported perimenstrual acne flare: 58.5% before menses, 35% during menses, and 6.5% after menses. Conclusion This study supports the concept that acne is associated with menstrual symptoms. Physicians should consider screening for menstrual symptoms among young women with acne.
... A routine approach to the management of patients with hyperandrogenism signs is an endocrine evaluation, comprising tests such as DHEAS, total and free testosterone, and LH/FSH ratio. Although women with hyperandrogenism should receive hormonal therapy, women with normal serum androgen levels also respond well to the treatment (14). Endocrinologic abnormalities are rare in acne patients but they can be the only clinical sign of androgen excess in women (15). ...
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Background One of the significant signs that may occur in patients suffering from hyperandrogenism is acne. It is obvious that knowing the cause and exact reason of each sign helps the physician come up with better examination and conclusion regarding the symptoms related to hyperandrogenism. Methods We conducted a case-control study at the department of dermatology of Farshchian hospital in Hamadan, Iran, on 110 cases who continuously had been diagnosed with acne. The control subjects were outpatients that did not have acne but came to the clinic for consultation on dermatologic diseases other than hyperandrogenism. The patients were asked about the presence or absence of acne, age, menstrual regularity, body weight, height, hirsutism, androgenetic alopecia, family members with acne history, and food habits. Results Acne was strongly associated with higher BMI, alopecia, menstrual dysfunction, positive familial history, and overuse of sweet and fatty foods. There was no association between acne and hirsutism. Some degrees of overmatching may arise from choosing dermatologic control subjects as well as from inclusion of other complaints. Conclusions BMI, Alopecia, menstrual dysfunction, positive familial history, and overuse of sweet and fatty foods may influence the risk of acne.
... However, in the last 5 to 10 years it has achieved first-line status. [1][2][3][4][5] Common options in the United States include combined oral contraceptives (COCs) and spironolactone. Both agents inhibit binding of testosterone to androgen receptors, and conversion of testosterone to dihydrotestosterone; they also increase sex hormonebinding globulin, which reduces free testosterone in the blood. ...
Article
Therapeutic actives for acne have changed little in the last decade. Recognition that acne is an inflammatory condition, not an infectious one, has led to a call for reduction in antibiotic use, which has culminated in a re-evaluation of our nonantibiotic choices. Spironolactone and oral contraceptives have become more acceptable first-line choices, and earlier use of isotretinoin has been proposed.
... The most important etiology of acne is related to sex hormone increase in circulation and subsequently target organs (2). One of the other pathophysiological signs of acne is excess metabolic rate and basal metabolism (4,5). Some of the most important etiologic foods in these categories are those with higher carbohydrate and fatty contents. ...
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Background Role of insulin-like growth factor 1 (IGF1) and contributing cancer risk has been shown in many studies. Hence, this study was performed to determine the serum level of IGF-1 in patients with acne vulgaris in comparison with healthy subjects. Methods The current study was a case-control assessment performed on a sample of 102 subjects, including 51 known cases of acne and 51 healthy subjects (without acne as controls). Serum IGF-1 level was assessed and compared across the two groups. Results Both groups were matched for age and gender (P > 0.05). The mean IGF-1 level was significantly (P = 0.0001) higher in the case group. There was a significant reverse correlation between age and serum IGF-1 level (P = 0.002, r = -0.417). Also, the mean serum IGF-1 level was significantly higher in males compared with females in the case group (P = 0.006). The severity and location of acne had no association with serum IGF-1 level (P > 0.05). Conclusions Overall, according to the obtained results in this study, it may be concluded that rate of metabolism is increased in patients with acne. This finding suggests that nutrition-related lifestyle factors play a role in acne pathogenesis. Hence, modifications in these styles are recommended to control acne formation. Also, use of IGF-1-reducing drugs, such as metformin, may be useful for treatment of acne. However, this matter may be confirmed by future studies.
... It can be effective for the treatment of acne, hirsutism and alopecia; however, hepatic toxicity limits the use of flutamide for acne as cases of fatal hepatitis have been reported. 56 ...
Article
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Niti Khunger, Krati Mehrotra Department of Dermatology and STD, Vardhman Mahavir Medical College, Safdarjang Hospital, New Delhi, IndiaCorrespondence: Niti KhungerDepartment of Dermatology and STD, Vardhman Mahavir Medical College, Safdarjang Hospital, Ring Road, New Delhi 110029, IndiaEmail drniti@rediffmail.comAbstract: Although acne is a disease predominant in adolescence, it is being increasingly observed in adult life, including the menopausal period. The etiology of menopausal acne is multifactorial, with hormonal imbalance being the major culprit. There is a relative increase of androgens in the menopausal female that leads to clinical hyperandrogenism manifesting as acne, hirsutism and androgenetic alopecia. Other endocrine disorders including thyroid abnormalities, hyperprolactinemia and insulin resistance also play a role. Genetics, stress, dietary changes, lack of sleep and exercise and other lifestyle changes are implicated as trigger factors. Most menopausal women with isolated few acne lesions have normoandrogenic serum levels and do not require extensive investigations. However, baseline investigations including total testosterone are useful. Patients must also be evaluated for associated comorbidities such as obesity, diabetes, hypertension and dyslipidemia. A detailed history can help to exclude polycystic ovarian syndrome, late-onset congenital adrenal hyperplasia or medications as a cause of acne. The evaluation of menopausal acne and the approach to treatment depend on the severity of acne and associated features. In patients with mild acne without virilization, prolonged topical therapy is the mainstay of treatment. Though combined oral contraceptives are effective, they are relatively contraindicated in the postmenopausal period. Spironolactone is the first choice of therapy in the subset of patients that require oral anti-androgen therapy. Procedural treatment can be useful as it can also help in the treatment of associated acne scars and concomitant skin aging. It is also important to focus on lifestyle changes such as reducing stress, controlling obesity, having a healthy diet, exercise and proper skin care routine to reduce acne. The focus of this article is on the clinical presentation and management challenges of menopausal acne, which represents a special subtype of acne.Keywords: acne, adult, menopause, hormonal, hyperandrogenism
... En cas de résistance à la doxycycline, il est possible de donner la minocycline, car les résistances croisées sont rares dans ce cas [1]. Si le traitement se prolonge au-delà de deux mois, même avec un antibiotique systémique, il faut [7]. L'effet du traitement ne peut être apprécié qu'après deux à quatre mois. ...
... Spezifische Therapien können bei einem Hyperandrogenismus mit Virilisierung mit den Androgenantagonisten Cyproteronacetat, 2-100 mg/d (2 mg sind enthalten in Diane-35 ® , Feminac 35 ® oder Minerva ® , 10 mg in Androcur-10 ® und 50 mg in Androcur ® ), oder Spironolacton (Aldactone ® ), 25-200 mg/d (EBM-Evidenzgrad B), durchgeführt werden. Vor Beginn der Therapie muss bei beiden Präparaten ein negativer Schwangerschaftstest vorliegen und eine Antikonzeption durchgeführt werden, da es durch die Verwendung der entsprechenden Präparate bei männlichen Föten zu einer Feminisierung kommen kann [7]. Die Wirkung der Therapie lässt sich erst nach zwei bis vier Monaten beurteilen. ...
... Ce rôle se manifeste par un effet antigonadotrope, caractérisé par une suppression de l'ovulation entrainant une inhibition de la production ovarienne d'androgènes. Cela permet de réduire la concentration sérique d'androgène et de diminuer la production de sébum (Thiboutot et Chen, 2003 ;Lai et al., 2012 ;Thiboutot, 2004). ...
Thesis
L’acné représente l’un des motifs de consultation les plus fréquents en dermatologie, notamment chezl’adolescent et le jeune adulte. Cette pathologie est complexe et multiparamétrique et, à ce titre, cemémoire présente les mécanismes impliqués dans la pathogenèse de l’acné, les facteurs de risquesassociés et les effets des médicaments utilisés dans le traitement de l’acné en France.La pathogénie de l’acné fait intervenir plusieurs groupes de mécanismes que sont une hyperséborrhéeavec une modification de la composition du sébum, une hyperkératinisation des follicules pilosébacés,une amplification de la colonisation de ces follicules par la bactérie Propionibacterium acnesainsi qu’une réaction inflammatoire. La chronologie de ces événements reste incertaine. Cependant,l’activité de la glande sébacée et la qualité du sébum produits ont un rôle central dans cettepathogenèse et de fait sont sans doute le point de départ du développement de la pathologie.L’activité des sébocytes présents dans les glandes sébacées sont sous l’influence de nombreusesmolécules telles que des hormones, des facteurs de croissance ou des neuropeptides. La modificationdes taux de ces molécules chez le patient acnéique en comparaison aux sujets sains conditionne ledéveloppement de l’acné. Les androgènes et l’IGF-1 ont par exemple un rôle important dansl’apparition de l’acné à l’adolescence.Mais, ces mécanismes pathogéniques sont également sous l’influence de divers facteurs de risques(alimentation, stress, soleil, tabac…). Une mise au point des connaissances actuelles, de l’implicationet des mécanismes par lesquels le mode de vie et le patrimoine génétique influent sur ledéveloppement l’acné est présentée dans ce mémoireEnfin, il est également question de comprendre comment les médicaments permettent une réductiondes lésions d’acné, et de passer en revue les recommandations actuelles d’utilisation de cesmédicaments pour traiter le plus efficacement les patients acnéiques.
... And increased DHT may act on infundibular keratinocytes leading to abnormal hyperkeratinization. If abnormal hyperkeratinization occur in keratinocytes, sebum production increases excessively in sebaceous gland [15][16][17]. 5α-reductase converts DHT from testosterone. Thus, inhibition of 5α-reductase activity improves AV by reducing ...
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Quercus mongolica (QM)—a member of the Fagaceae family—has been used as traditional medicine in Korea, China and Mongolia as a treatment for inflammation of oral, genital or anal mucosa and for external inflammation of skin. To treat acne vulgaris (AV), we evaluated the inhibition of inflammatory cytokines (IL-6 and IL-8) of QM leaf extract (QML) and its main compound, pedunculagin (PD) in vitro and 5α-reductase inhibitory activity by western blotting. As results, QML and PD showed potent NO production inhibitory activity compared with the positive control (PC), NG-monomethyl-L-arginine (L-NMMA). QML and PD was also showed the decreases of IL-6 and IL-8 compared with the PC, EGCG and exhibited potent 5α-reductase type 1 inhibitory activities compared with the PC, dutasteride.
... The response to therapy with SPL is usually evident after 3 months of initiation of treatment with SPL. [25][26][27] Apart from its beneficial role in facial acne SPL has also shown to be effective in truncal acne. [28] Once the desired endpoint of control of acne lesions has been obtained, maintenance dosing of SPL ranging from 25 to 50 mg/day maybe particularly beneficial in those women who tend to have sporadic outbreaks of inflammatory or isolated nodulocystic lesions. ...
... Presence of bacteria, heat, oil, and dirt is responsible for the generation of this acne type. Inflammatory lesions of size below 5 mm may also be present in the affected area [8]. ...
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Background: Acne is a multifactorial skin disease associated with pilosebaceous unit and caused by bacteria Propionibacterium acnes and Acne vulgaris. Near about 95% people throughout the world suffer from acne at some point in their life span. This disease is more prominent in adults compared to neonates and prepubescent children. Conventionally it is treated with either creams or gels having large number of side effects on patients. Methods: We searched about recent advancements in the use of nanotechnological carriers for effective treatment of acne. We focused on the use of liposomes, niosomes, microemulsions, microsponge, microspheres, and nanoparticles to improve anti-acne therapy. Results: The encapsulation of anti-acne drugs in various nanotechnological carriers improve their efficacy and reduce side effects. These carriers show controlled drug release and improved drug penetration even upto pilosebaceous unit of skin. Local tolerability of anti-acne molecules can be improved by adjusting the concentration in nanotechnological carriers. Conclusions: Nanotechnological carriers have opened a new window to design novel, effective and low dose systems for effective eradication acne disease. However, very few nanocarrier based formulations are available in market for topical use and much progress is required in this field to improve anti-acne therapy.
... It is not a life-threatening condition but it lasts for years and causes physical and emotional stress. 1 Successful management of acne involves choosing right medication according to the type of acne: mild, moderate, or severe. 2 Chemical peeling is a documented option in the treatment of active acne. The mechanism of action lies in causing desquamation by targeting the corneosomes and keratinocytes, enhancing breakdown and decreasing cohesiveness. ...
Article
Background Successful management of acne involves choosing proper medication. Chemical peeling is a well‐known option in treatment of acne vulgaris. Objective To evaluate and compare the clinical efficacy and safety of combination chemical peels vs single peel in treatment of mild‐to‐moderate acne. Methods The study included 45 patients with mild‐to‐moderate acne divided into three equal groups. Group A underwent combination sequential peels with modified Jessner's solution (MJ) followed by trichloro acetic acid (TCA20%) on the right (Rt) side of the face vs TCA 30% on the left (Lt) side. Group B was treated by combination peels of salicylic (20%) mandelic (10%) (SM) mixture on the Rt half vs salicylic acid 30% on the Lt half. Group C underwent combination sequential peeling of MJ and TCA on the Rt side vs SM combination peels on the Lt side. All patients received six sessions with 2‐week intervals and followed up for 3 months after the last session. Side effects were reported. Results Both sides of the face showed significant improvement of acne lesions but improvement was significantly higher and earlier in sides treated by combination peels. Side effects were minimal. Conclusion In conclusion, combination peels achieved a higher and earlier therapeutic response with a reasonable cost that is maintained for a relatively long periods than single peel. Combination sequential peels gave the best results.
... 15 The inner glandular layer starts presenting an increase in colonization by Propionibacterium acnes, a Gram-positive bacteria responsible for the onset of the inflammatory process. [16][17][18] New data have disclosed that the development of lesions is related to the activation of the innate immunity, and that this process can occur even before follicular hyperkeratinization. [18][19][20][21][22][23][24][25][26] Histopathological and immunohistochemical investigations confirm that a lymphocytic infiltrate composed of memory and effector T-cells is the first finding at the beginning of the disease. 27,28 Jeremy et al showed the existence of a center-follicular inflammatory process before the development of the microcomedo. ...
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Acne is a multifactorial and inflammatory disease of pilosebaceous follicles, which affects most adolescents. Recent epidemiological data revealed a difference in adults affected by this disease. Women have a high prevalence and incidence when compared with men, especially after 25 years of age. In contrast to what was initially thought, most of these patients do not present endocrinopathy capable of leading to the development of the lesions. When present, polycystic ovarian syndrome is the main cause. However, in these cases, acne is rarely the only dermatological manifestation; hirsutism and acanthosis nigricans are often present. The majority of the normoandrogenic acne patients present a history since adolescence, but in many cases the lesion distribution and intensity change with time. There is often a typical localization of the lesions in the lower third of the face and lateral region of the neck. Another interesting feature is related to the impact on quality of life (QoL), which is always intense. Often there are signs of depression, even when the lesions are mild. As most adult patients are women, in addition to the conventional options, there is also hormone treatment. Combined oral contraceptives and spironolactone are good options. Knowing more about the particularities in etiopathogenesis, impact on QoL, and specific treatment options is important to all dermatologists who face the challenge of treating acne in adults.
... Androgens play a major role (Harper, 2008;Lucky et al., 1994Lucky et al., , 1997, as evidenced by the response of acne in adult women to hormonal treatments, especially in the context of hyperandrogenism disorders such as polycystic ovary syndrome (PCOS) and the use of hormone-based therapies such as oral contraceptive and anti-androgen medications in women with normal androgen levels (Lolis et al., 2009). In addition, the lack of acne in androgen-insensitive women (Imperato-McGinley et al., 1993;Thiboutot, 2004) and rising levels of dehydroepiandrosterone sulfate in association with the onset of acne in premenarchal girls and a subset of patients with PCOS also play a major role (Lucky et al., 1994;Chen et al., 2011). Androgens stimulate sebum production via androgen receptors on the sebaceous glands. ...
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This review focuses on the treatment options for adult female patients with acne. Acne in adult female patients may start during adolescence and persist or have an onset in adulthood. Acne has various psychosocial effects that impact patients' quality of life. Treatment of acne in adult women specifically has its challenges due to the considerations of patient preferences, pregnancy, and lactation. Treatments vary widely and treatment should be tailored specifically for each individual woman. We review conventional therapies with high levels of evidence, additional treatments with support from cohort studies and case reports, complementary and/or alternative therapies, and new agents under development for the treatment of patients with acne.
... Several other studies show that women with acne have elevated levels of free testosterone and total testosterone, though this same relationship is not seen in men [83]. Estrogen can counter androgens through negative feedback loops, suggesting that increasing dietary phytoestrogens may be a better solution than attempting to decrease testosterone, which can have negative effects on male fertility since testosterone is necessary for spermatogenesis [84][85][86]. Estrogen seems to have a beneficial effect on skin, decreasing sebaceous gland size, sebum production and acne [87,88]. ...
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Acne vulgaris affects most people at some point in their lives. Due to unclear etiology, likely with multiple factors, targeted and low-risk treatments have yet to be developed. In this review, we explore the multiple causes of acne and how plant-based foods and supplements can control these. The proposed causative factors include insulin resistance, sex hormone imbalances, inflammation and microbial dysbiosis. There is an emerging body of work on the human gut microbiome and how it mediates feedback between the foods we eat and our bodies. The gut microbiome is also an important mediator of inflammation in the gut and systemically. A low-glycemic load diet, one rich in plant fibers and low in processed foods, has been linked to an improvement in acne, possibly through gut changes or attenuation of insulin levels. Though there is much interest in the human microbiome, there is much more unknown, especially along the gut-skin axis. Collectively, the evidence suggests that approaches such as plant-based foods and supplements may be a viable alternative to the current first line standard of care for moderate acne, which typically includes antibiotics. Though patient compliance with major dietary changes is likely much lower than with medications, it is a treatment avenue that warrants further study and development.
... Furthermore, clinical studies proved the increased activity of type I 5-alpha-reductase in keratinocytes from patients with acne, which led to increased production of active androgens. Studies carried out with men and women reported that, when the levels of these hormones were unstable, acne can worsen [12,30]. ...
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In addition to dermatological complications, acne can affect the quality of life of individuals in numerous ways, such as employment, social habits and body dissatisfaction. According to our expertise, caprylic acid and propanediol would not have a direct action on Cutibacterium acnes. Despite this, we investigated the existence of a synergistic effect among xylitol, caprylic acid and propanediol as a mixture of compounds representing a single topical active ingredient that could benefit the treatment against acne. In vitro and in vivo assays were performed to challenge and to prove the efficacy of propanediol, xylitol and caprylic acid (PXCA) against acne. PXCA had its MIC challenged against C. acnes (formerly Propionibacterium acnes) and Staphylococcus aureus, resulting in concentrations of 0.125% and 0.25%, respectively, and it also developed antimicrobial activity against C. acnes (time-kill test). PXCA was able to reduce the 5-alpha reductase expression in 24% (p < 0.01) in comparison with the testosterone group. By the end of 28 days of treatment, the compound reduced the skin oiliness, porphyrin amount and the quantity of inflammatory lesions in participants. According to the dermatologist evaluation, PXCA improved the skin's general appearance, acne presence and size.
... Flutamide{2-methyl-N-[-nitro-3-(trifluoromethyl) phenyl]propanamide)} which comes under the class of cytostatic, is extensively used as a non-steroidal anti-androgen drug as a cure for advanced prostate cancer (NARAYANA et al., 1981). Besides, this has also been used in hormonal treatment in female (Thiboutot, 2004;Jing and Anjali, 2016). Upon the oral consumption of the flutamide drug, flutamide and its metabolites gets distributed to the ven-tral prostate and seminal vesicle regions and the metabolism takes place. ...
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Flutamide is a man-made non-steroidal anti-androgen drug that is extensively used for the prostate cancer therapy. Though the drug has a higher benefit ratio in treating cancer, it also exhibits certain lethal side effects to humans. It acts as an environmental pollutant instigating water pollution and aquatic organism damage by interfering in their reproductive cycle and its effect on aquatic life is a major concern. Hence, it is mandatory to detect the presence of this nitro-aromatic compound. For the effective determination of this analyte, gold modified Polyhedral Oligomeric Silsesquioxane (abbreviated as POSS-S-Au) based organic-inorganic hybrid material as chemical modifier has been used. This material synthesized via a hydrolysis-condensation reaction technique followed by a phase transfer method is utilized for the first time in the electrochemical determination of anti-cancer drug. The as-synthesized nanomaterial has been subjected to various Physio-chemical characterization and the Fourier Transform- Infrared Spectroscopy (FT-IR) spectra confirm the presence of -SH organic group and Si-O-Si stretch. X-ray Photoelectron Spectroscopy (XPS) spectra affirms the presence of silicon, oxygen, gold, and Sulphur owing to the introduction of gold through the thiolation of silicate core. The fabricated sensor showed excellent electro-catalytic activity for detecting flutamide with limit of detection (LOD) of 0.12 M, and higher sensitivity of around 0.048 A/M.
... Supplying sufficient amounts of estrogens will decrease sebum production and may act by suppressing androgen production by inhibiting the pituitary from secreting gonadotropin. 4 The effect of progesterone on sebaceous glands was still disputed. Some authors have blamed progesterone for the change of sebum production in females during the menstrual cycle. ...
Article
Introduction: Acne is a chronic inflammatory disorder of the pilosebaceous unit with differential pathogenesis. To elucidate the roles of hormones in acne pathogenesis, we conducted a study to evaluate the serum testosterone, estradiol, progesterone levels in women with acne vulgaris. Methods: We conducted a cross-sectional descriptive study, and 175 women with acne vulgaris were examined; their serum estradiol, progesterone, testosterone were analyzed by chemiluminescence technique and compared with the healthy control group. Results: Increased serum hormone levels in women with acne vulgaris were accounted for 29.7%, and hyperandrogenism was accounted for 16.0% of cases. We found significant differences in testosterone levels (mean value, 55.67±25.56 versus 38.37±10.16 ng/dL, p<0.05) respectively in the acne group and the control group. However, the estradiol level of the acne group (323.15±93.31 pmol/L) was lower than the control group (370.94±58.88 pmol/L) with p<0.05). No statistically significant differences were found for progesterone (0.60±0.38 versus 0.50±0.15 ng/mL, p>0.05) levels. Moreover, we did not find the relationship between serum hormone levels and the severity of acne vulgaris. Conclusion: This study showed that the female acne vulgaris patients may have high serum testosterone levels and low serum estradiol levels compared with those of female controls. However, hormone alterations had no correlation with the acne grades.
... Consistent with the association between acne and puberty, hormones influence both acne development and severity. 3 The exogenous ingestion of either androgens or growth hormone often causes acne. 4,5 Similarly, when these hormone levels are endogenously elevated, such as androgens in patients with polycystic ovarian syndrome or growth hormone in patients with acromegaly, acne occurs more commonly. ...
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Background Acne vulgaris is a common cutaneous disorder. Diet and metabolism, specifically glycemic content and dairy, influence hormones such as insulin, insulin-like growth factor 1, and androgens, which affect acnegenesis. Objective To systematically review high-quality evidence regarding the association of dietary glycemic and dairy intake with acnegenesis. Methods A comprehensive literature search, without timeline restriction, of MEDLINE (completed between October and November 2021) for English-language papers that examined the association between diet and acne was conducted. The evidence quality was assessed using the Ottawa quality assessment scale. Results The literature search yielded 410 articles, of which 34 articles met the inclusion criteria. The literature on whether dairy product intake is associated with acnegenesis is mixed and may be dependent on sex, ethnicity, and cultural dietary habits. High glycemic index and increased daily glycemic load intake were positively associated with acnegenesis and acne severity, an observation supported by randomized controlled trials. Conclusion High glycemic index, increased glycemic load, and carbohydrate intake have a modest yet significant proacnegenic effect. Increased dairy consumption may have been proacnegenic in select populations, such as those in which a Western diet is prevalent. The impact of diet on acnegenesis is likely dependent on sex and ethnicity. Further randomized trials are necessary to fully characterize the potential associations.
... To exemplify, at least two locations of acne (most commonly: thorax, shoulders, jaw, neck and cheeks) were associated with irregular menstrual cycles and intense seborrhea of the face and scalp. Thus, the presence of acne on those sites, accompanied by intense facial seborrhea, hirsutism and irregular menses could reveal endocrine disorders that should be thoroughly investigated (22,23). ...
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Acne is a disorder of the pilosebaceous unit, common among adolescents, which may be extended to adulthood. The aim of this study was to assess the prevalence of hormonal disorders in women with acne resistance to conventional therapy. We included 72 women aged between 15 and 36 years (divided in two age groups) who presented to our clinic between May and October 2014, suffering from moderate and severe forms of papulopustular and nodulocystic acne. The subjects were non‑responsive to classic dermatological treatment or had clinical manifestation of hyperandrogenism. Based on age, we divided the women into two groups, group I with 40 patients aged 15‑22 years and group II with 32 patients aged 23-36 years. Using ELISA, a hormonal profile was performed for each patient in days 1‑3 of the menstrual cycle including, total testosterone, dehydroepiandrosterone sulfate (DHEA‑S), follicle‑stimulating hormone (FSH), luteinizing hormone (LH), estradiol, prolactin, and plasma cortisol. For statistical analysis we used Stata 13 software. We compared the hormonal profile of the two groups and identified significant differences for: testosterone levels (mean value, 0.64±0.35 vs. 0.97±0.50 ng/ml; p<0.0001), DHEA‑S levels (mean value, 0.85±0.27 vs. 1.05±0.33 mg/24 h; p=0.001), prolactin levels (mean value, 281.85±91.113 vs. 353.969±102.841 mIU/ml; p=0.002) and LH levels (14.8±6.7 vs. 20.1±8.2 mIU/ml; p=0.002) were higher in group Ⅱ. No statistically significant differences were found for estradiol (p=0.588) and cortisol (p=0.182) levels. In conclusion, refractory acne can be the first sign of systemic illness including polycystic ovary syndrome. Thus, for a correct therapeutic approach it is necessary to interpret the clinical and biochemical elements in correlation with the medical history.
Article
Background: Glycemic index (GI) and glycemic load (GL) may be implicated in acne pathogenesis. Objective: This cross-sectional study examined differences between GI/GL and biological factors associated with acne among adults with and without moderate/severe acne. Secondary objectives included examining differences between food-aggravated acne beliefs and acne-specific quality of life among adults with and without moderate/severe acne. Design: As part of a cross-sectional study, participants completed a 5-day food record; blood draw to measure biological factors associated with acne (ie, glucose, insulin, insulin-like growth factor-1, insulin-like growth factor binding protein-3, and sex hormone-binding globulin concentrations); body composition assessment; and questionnaire to evaluate food-aggravated acne beliefs and acne-specific quality of life. Food records were analyzed using Nutrition Data Services for Research. Participants: Sixty-four participants (no acne, n=32; moderate/severe acne, n=32) from New York City, NY, were included in this study. Statistical analysis: Independent sample t tests and Mann-Whitney tests examined differences in anthropometric measurements, dietary intakes, biological factors associated with acne, insulin resistance, and acne-specific quality of life between acne groups. A χ(2) test for independence assessed differences in food-aggravated acne beliefs between acne groups. Results: Participants with moderate/severe acne consumed greater total carbohydrate (P=0.003), available carbohydrate (P<0.001), percent energy from carbohydrate (P<0.001), and GL (P<0.001) compared to participants without acne. Participants with moderate/severe acne had greater insulin (P=0.002) and insulin-like growth factor-1 (P=0.009) concentrations, greater insulin resistance (P=0.001), and lower sex hormone-binding globulin (P=0.015) concentrations compared to participants without acne. Although there were no differences between groups, 61% of participants reported food-influenced acne. Participants with moderate/severe acne reported a lower quality of life compared to participants without acne (P<0.001). Conclusions: The results from this cross-sectional study suggest a relationship between dietary carbohydrate, including GL, and acne. Future research is necessary to determine the effect of medical nutrition therapy on biological factors associated with acne and acne severity.
Article
Background Little is known about how dermatologists prescribe hormonal antiandrogen acne treatment (HAAT). Objective The aim of this study was to investigate dermatologists’ HAAT-prescribing habits and HAAT’s impact on systemic antibiotic use in women with acne. Methods We performed a retrospective study at an academic medical center of female patients receiving HAAT (combined oral contraceptive [COC], spironolactone) for acne from January 2005 to October 2015. Data from a control group of female acne patients who never received HAAT were also collected. ResultsA total of 672 female patients received HAAT. Out of all systemic medications for acne, antibiotics were used as first-line treatment in 39% of patients, COCs in 12%, and spironolactone in 21%. Mean antibiotic durations in patients who initiated HAAT for the first time at the study site (250.4 days) were significantly longer than in patients who received HAAT prior to presentation and continued HAAT at the study site (192.0 days) (p = 0.021). A statistically significant inverse association was found between HAAT use and mean antibiotic duration (p = 0.016). ConclusionsHAAT is not typically used as a first-line systemic therapy in women with acne. HAAT usage is associated with shorter cumulative antibiotic durations and early HAAT initiation can decrease systemic antibiotic use in acne treatment.
Chapter
Acne represents the commonest inflammatory dermatosis seen worldwide and is the leading reason for seeing a dermatologist; a number of acne variants are described. In children, these include neonatal, infantile, mid-childhood and prepubertal acne. Acne fulminans and acne conglobata represent severe but rare forms. Predisposing factors may be implicated in acneform dermatoses; these include medications, occupational and environmental triggers, cosmetics, systemic diseases and syndromes. This chapter describes all clinical variants and provides evidence-based or expert opinion on management.
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RESUMO: A acne vulgaris é classificada como a 8ª patologia mais comum em todo o mundo, com uma prevalência estimada de 9,4% globalmente. Ela afeta indivíduos da maioria das idades, no entanto, a prevalência mostra um pico significativo na adolescência. É considerada uma doença inflamatória crônica da unidade pilossebácea multifatorial, envolvendo fatores genéticos, desequilíbrio hormonal, aumento da produção de sebo, queratinização anormal e proliferação bacteriana. E, embora os fatores dietéticos tenham sido considerados sem importância, evidências apoiam o papel da nutrição como um fator predisponente na manifestação da acne. O presente estudo tem como objetivo realizar uma revisão integrativa explorando a associação entre a acne, a ingestão de laticínios (leite, iogurte, queijo), subgrupos de laticínios (gordura total, baixo teor de gordura, desnatado) e o uso de whey protein como suplementação proteica. Optou-se a realização de uma revisão integrativa de literatura que contemplasse a seguinte questão de pesquisa: “Qual a influência dos laticínios e da suplementação proteica em pacientes com diagnóstico de acne?”. A busca na literatura foi realizada na Medical Publisher (PUBMED), Science Direct e na Scientific Eletronic Library (SCIELO). Verificou-se que há evidências que demonstram a correlação do leite, seus derivados e das proteínas do leite “whey protein” na ocorrência da acne vulgar, sendo maior em indivíduos do gênero masculino. Os achados apontam para uma significativa correlação entre a influência dos laticínios e da suplementação proteica na manifestação da acne, mostrando uma maior incidência em indivíduos que fazem o uso de Whey Protein, consumo este popularizado na atualidade e disseminado na população mais jovem, que busca o ganho de massa corporal, desconhecendo os contras do uso desse tipo de susbstância.
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Although most teenagers experience acne, for sexual and gender minority teenagers, acne could be more challenging and require specific psychosocial considerations. Acne may be more strongly associated with mental health issues in sexual and gender minority adolescents. Acne development during puberty may trigger gender dysphoria in transgender patients. Transgender and gender nonbinary patients receiving testosterone therapy may experience new or worsening acne. Comprehensive care for moderate to severe acne in sexual and gender minority adolescents should include culturally competent discussions about sexual behaviors, contraception, and/or gender-affirmation treatment plans.
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Androgen-mediated cutaneous disorders (AMCDs) in women, including acne, hirsutism, and female pattern hair loss, can be treated with hormone-modulating therapies. In the second article in this Continuing Medical Education series, we discuss the hormone-modulating therapies available to dermatologists for the treatment of AMCDs, including combined oral contraceptives, spironolactone, finasteride, dutasteride, and flutamide. Available hormone-modulating treatments used for each AMCDs are reviewed, along with mechanisms of androgen modulation, safety profile, contraindications, monitoring parameters, and evidence of efficacy. Medications discussed include those that are approved by the US Food and Drug Administration for certain AMCDs and some that are used off-label. Despite the ubiquity of hormone-modulating therapies used for AMCDs, this review highlights the need for more rigorous studies to evaluate these therapies for acne, hirsutism, and female pattern hair loss.
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Introduction: Acne is a chronic inflammatory disorder of the pilosebaceous unit with differential pathogenesis. To elucidate the roles of hormones in acne pathogenesis, we conducted a study to evaluate the serum testosterone, estradiol, progesterone levels in women with acne vulgaris. Methods: We conducted a cross-sectional descriptive study, and 175 women with acne vulgaris were examined; their serum estradiol, progesterone, testosterone were analyzed by chemiluminescence technique and compared with the healthy control group. Results: Increased serum hormone levels in women with acne vulgaris were accounted for 29.7%, and hyperandrogenism was accounted for 16.0% of cases. We found significant differences in testosterone levels (mean value, 55.67±25.56 versus 38.37±10.16 ng/dL, p<0.05) respectively in the acne group and the control group. However, the estradiol level of the acne group (323.15±93.31 pmol/L) was lower than the control group (370.94±58.88 pmol/L) with p<0.05). No statistically significant differences were found for progesterone (0.60±0.38 versus 0.50±0.15 ng/mL, p>0.05) levels. Moreover, we did not find the relationship between serum hormone levels and the severity of acne vulgaris. Conclusion: This study showed that the female acne vulgaris patients may have high serum testosterone levels and low serum estradiol levels compared with those of female controls. However, hormone alterations had no correlation with the acne grades.
Article
Introduction: Acne is a chronic inflammatory disorder of the pilosebaceous unit with differential pathogenesis. To elucidate the roles of hormones in acne pathogenesis, we conducted a study to evaluate the serum testosterone, estradiol, progesterone levels in women with acne vulgaris. Methods: We conducted a cross-sectional descriptive study, and 175 women with acne vulgaris were examined; their serum estradiol, progesterone, testosterone were analyzed by chemiluminescence technique and compared with the healthy control group. Results: Increased serum hormone levels in women with acne vulgaris were accounted for 29.7%, and hyperandrogenism was accounted for 16.0% of cases. We found significant differences in testosterone levels (mean value, 55.67±25.56 versus 38.37±10.16 ng/dL, p<0.05) respectively in the acne group and the control group. However, the estradiol level of the acne group (323.15±93.31 pmol/L) was lower than the control group (370.94±58.88 pmol/L) with p<0.05). No statistically significant differences were found for progesterone (0.60±0.38 versus 0.50±0.15 ng/mL, p>0.05) levels. Moreover, we did not find the relationship between serum hormone levels and the severity of acne vulgaris. Conclusion: This study showed that the female acne vulgaris patients may have high serum testosterone levels and low serum estradiol levels compared with those of female controls. However, hormone alterations had no correlation with the acne grades.
Article
The article presents the results of evaluating the effectiveness of the combined use of combined oral contraceptives (COC) and Skinoren cream in severe papular-pustular and moderate nodular-cystic acne. Material and methods. Patients of the first group (n = 11) used COC and an external antibacterial drug two times a day for the treatment of acne. Patients of the second group (n = 12) used COC and an external drug containing azelaic acid (Skinoren) for the treatment of acne two times a day. The duration of follow-up was 6 months. The efficiency assessment was carried out taking into account the dynamics of the indicators of the IGA (Investors Global Assessment) scale. The Manchester Scar Scale (MSS) was used to assess the effectiveness of post-acne correction. In addition, the effectiveness was evaluated based on the results of the mexametry. Results. When evaluating IGA in the comparison groups in patients with severe papulopustular acne and moderate nodular cystic acne, comparable efficacy was noted, but the best results were recorded in the COC + Skinoren group (p < 0.05). No effect and deterioration of the condition were observed in any group. When assessing MSS, the most pronounced changes were observed in patients of group 2, where the combination of COC + Skinoren was used. So, in group 1, the severity of scars decreased by 42.3 %, in group 2 by 48.2 % (p < 0.05). The evaluation of the results of the mexametry showed a more pronounced decrease in the amount of pigment in patients from group 2. When studying the results of the severity of erythema, the dynamics similar to the severity of the pigment was obtained. The best result was registered in group 2 (COC + Skinoren) (p < 0.05). Conclusions. The combined use of COC and Skinoren cream for severe papular-pustular and moderate nodular-cystic acne has proven to be an effective method both in relation to the number of inflammatory and retention elements, and in relation to hyperpigmentation.
Chapter
Skin and its appendages make up the integumentary system. It is the largest organ of the body that constitutes about 15–20% of the body weight with a surface area less than 1.5 m2. In this chapter, anatomy and organization of the skin has been described.
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Flutamide is a man-made non-steroidal anti-androgen drug that is extensively used for the prostate cancer therapy. Though the drug has a higher benefit ratio in treating cancer, it also exhibits certain lethal side effects to humans. It acts as an environmental pollutant instigating water pollution and aquatic organism damage by interfering in their reproductive cycle and its effect on aquatic life is a major concern. Hence, it is mandatory to detect the presence of this nitro-aromatic compound. For the effective determination of this analyte, gold modified Polyhedral Oligomeric Silsesquioxane (abbreviated as POSS-S-Au) based organic-inorganic hybrid material as chemical modifier has been used. This material synthesized via a hydrolysis-condensation reaction technique followed by a phase transfer method is utilized for the first time in the electrochemical determination of anti-cancer drug. The as-synthesized nanomaterial has been subjected to various Physio-chemical characterization and the Fourier Transform- Infrared Spectroscopy (FT-IR) spectra confirm the presence of -SH organic group and Si-O-Si stretch. X-ray Photoelectron Spectroscopy (XPS) spectra affirms the presence of silicon, oxygen, gold, and Sulphur owing to the introduction of gold through the thiolation of silicate core. The fabricated sensor showed excellent electro-catalytic activity for detecting flutamide with limit of detection (LOD) of 0.12 µM, and higher sensitivity of around 0.048 µA/µM.
Chapter
The androgen receptor (AR) mediates the endocrine functions of endogenous androgens like testosterone and exerts pleiotropic androgenic (male phenotype development, sexual function) and anabolic (growth and maintenance of musculoskeletal system) effects across most tissues. The AR‐axis, i.e. AR and its downstream effects, is extensively targeted to stimulate anabolism or treat prostatic diseases. Tissue‐selective, direct‐acting synthetic AR agonists are limited in scope by their inadequate separation of anabolic from untoward androgenic or virilizing effects and include FDA approved steroidal androgens (anabolic‐androgenic steroids) and investigational nonsteroidal selective AR modulators (SARMs). Gaining in popularity is testosterone replacement therapy in hypogonadal men. Antagonism of the AR‐axis is common in aging males with androgen‐dependent prostate hyperproliferation [prostate cancer or benign prostatic hyperplasia (BPH)]. Androgen ablation (indirect antagonism) and direct AR antagonism have been the mainstays of prostate cancer therapies for many decades including recent approvals. Indirect antagonists of the AR‐axis include gonadotropin‐releasing hormone agonists or antagonists (androgen‐deprivation therapy), which achieve systemic androgen and estrogen ablation for prostate or breast cancers as a monotherapy or sometimes in combination with steroidogenic enzyme (lyase) inhibitors. DHT‐dependent diseases are treated with 5α‐reductase to block intracrine production of DHT for male pattern baldness and BPH; whereas aromatase inhibitors block androgen metabolism to estrogen in breast cancer. Direct AR antagonists (antiandrogens) with improved potency and anti‐androgenic scope continue to be approved for prostate cancer. Research into innovative ways to directly or indirectly modulate the AR‐axis remains robust, suggesting new therapies will likely be introduced regularly for the foreseeable future.
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This study aims to clarify the antimicrobial behavior of ZnO nanoparticles contrary to Gram-positive and Gram-negative bacteria isolated from patients with acne. The effects of concentration of normal and nanoparticles of ZnO were detected by using microbiological experiments like well agar diffusion method. These tests were performed following standard method; and the concentration studied of normal particles were 5, 10, 15, 20 mg/ml,while the concentration of nanoparticles were 3.12, 6.25, 12.5, 25, 50 mg/ml. Out of 72 patientssuffered from skin infection; 60 only give positive results for bacterial growth, whose ages range between (18-23) years old. And the swabs were collected and transformed for microbiology lab at 20 min approximately. The bacteria isolated,distributed to (16) for each of Staphylococcus epidermidis and Staphlococcus aureus, (10) for each of Propionibacterium acnes and Pseudomonas aeroginosa, And Acinetobacter baumanii and Proteus mirabilis have (4) isolates for each one. The results revealed that, the antibacterial action of ZnO nanoparticles, have more effectiveness than normal particles at all except for S. epidermidis which show susceptibility and inhibition zone with the lower concentration of ZnO NaPs .
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Hormones play a significant role in normal skin physiology and many dermatologic conditions. As contraceptives and hormonal therapies continue to advance and increase in popularity, it is important for dermatologists to understand their mechanisms and dermatologic effects given the intricate interplay between hormones and the skin. This article reviews the dermatologic effects, both adverse and beneficial, of combined oral contraceptives (COCs), hormonal intrauterine devices (IUDs), implants, injections, and vaginal rings. Overall, the literature suggests that progesterone-only methods, such as implants and hormonal IUDs, tend to trigger or worsen many conditions, including acne, hirsutism, alopecia, and even rosacea. Therefore, it is worthwhile to obtain detailed medication and contraceptive histories on patients with these conditions. There is sufficient evidence that hormonal contraceptives, particularly COCs and vaginal rings, may effectively treat acne and hirsutism. While there are less data to support the role of hormonal contraceptives in other dermatologic disorders, they demonstrate potential in improving androgenetic alopecia and hidradenitis suppurativa.
Chapter
The skin is the interfacing barrier to the external environment. Its integrity is required for protection and health. The cells are continuously being replaced in response to both intrinsic and extrinsic forces. Diet and lifestyle affect the skin health. Genetic makeup, including microRNA, also impacts the degree of skin disease. The incorporation of adequate protein, essential fatty acids, low-glycemic carbohydrates, fermented foods, water, minerals, vitamins, and phytonutrient-rich vegetables modulate the endocrine and immunologic systems of the skin, providing the best opportunity for health. Nutritional requirements for this organ system vary widely depending on its state of health or condition. Common skin ailments are impacted by medical nutrition therapies that can alter the severity of the condition. The application of food and dietary choices, the modified elimination diet, and nutrient or bioactive supplementation may impact the root causes of the skin condition. Dermatologic conditions are common in clinical practice. Common conditions may be a result of underlying metabolic dysfunction (acanthosis nigricans); immunologic epigenetic perturbations (psoriasis and pemphigus); the gut-brain-skin axis dysfunction (acne vulgaris and acne rosacea); genetic or acquired deficiency (zinc and acrodermatitis enteropathica, follicular hyperkeratosis); food-triggered hypersensitivity (dermatitis herpetiformis); a multifactorial imbalance of genetic, environmental, innate, and acquired immune dysfunction (atopic dermatitis); and frank deficiency (pellagra, scurvy). These conditions may respond to targeted medical nutrition therapy. The therapeutic opportunities for each common condition are reviewed.
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Contraceptives that contain estrogen and/or progestins are used by millions of women around the world to prevent pregnancy. Owing to their unique physiological mechanism of action, many of these medications can also be used to prevent cancer and treat multiple general medical conditions that are common in women. We performed a comprehensive literature search. This article will describe the specific mechanisms of action and summarize the available data documenting how hormonal contraceptives can prevent ovarian and uterine cancer and be used to treat women with a variety of gynecological and nongynecological conditions such as endometriosis, uterine fibroids, heavy menstrual bleeding, polycystic ovary syndrome, acne, and migraines. Contraceptive methods containing estrogen and progestin can be used for a wide variety of medical issues in women.
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OBJECTIVE Acne vulgaris in female adolescents, when severe or accompanied by other signs of androgenization, may represent a sign of hyperandrogenemia often underdiagnosed, which will have harmful consequences for adult life. The objective of this cross-sectional and retrospective study was to demonstrate the incidence of hormonal changes in the cases of female adolescents with severe or extensive acne, with or without other signs of hyperandrogenism, and propose a hormonal research pattern which should be indicated in order to detect early hyperandrogenemia. METHODS The medical records of 38 female patients aged between 9 and 15 years old with grade II and/or III acne were analyzed. The dehydroepiandrosterone sulfate, dehydroepiandrostenedione, and androstenedione, total testosterone, and dihydrotestosterone sulfate hormones were required prior to initiation of treatment. The hormonal dosages were performed in the serum after at least 3 hours of fasting by means of radioimmunoassay tests. RESULTS Of the 38 patients included, 44.7% presented changes in androgen levels (hyperandrogenemia), and the two most frequently altered hormones were DHEA and androstenedione, with the same incidence (23.6%). CONCLUSIONS The correct and early diagnosis provides an effective and agile approach, including antiandrogen therapy, with the purpose of avoiding the reproductive and metabolic repercussions, besides controlling the inflammatory picture and avoid aesthetic complications.
Article
Objectives Cyproterone acetate is actually the first-line anti-androgenic treatment for severe hyperandrogenism in women. However, as this treatment is currently controversial, the objective of the study was to evaluate the safety and efficacy of spironolactone as a relay for cyproterone acetate. Methods This is a monocentric retrospective study conducted between December 2002 and January 2018 at the Jeanne de Flandre Hospital at the University Hospital Center of Lille. Patients with clinical hyperandrogenism who received treatment with cyproterone acetate and then spironolactone were included. A total of 37 patients were clinically and biologically evaluated before treatment, followed by cyproterone acetate and spironolactone. Results Clinically, the vast majority of patients were satisfied with the relay by spironolactone and found no difference between the two treatments. Biologically, testosterone and delta-4 androstenedione levels were significantly decreased with cyproterone acetate and spironolactone compared to no treatment. No significant differences were found when comparing levels under cyproterone acetate and under spironolactone. In addition, 87,5% of patients were free of side effects. Conclusions The data collected show the clinical and biological efficacy of spironolactone as a relay for cyproterone acetate in the treatment of hyperandrogenism. This anti-androgen therefore appears as an effective and well-tolerated alternative, as a relay for cyproterone acetate in patients with hyperandrogenism. Copyright © 2020. Published by Elsevier Masson SAS.
Article
Introduction: Acne is a chronic inflammatory disorder of the pilosebaceous unit with differential pathogenesis. To elucidate the roles of hormones in acne pathogenesis, we conducted a study to evaluate the serum testosterone, estradiol, and progesterone levels in women with acne vulgaris. Methods: We conducted a cross-sectional descriptive study, and 175 women with acne vulgaris were examined; their serum estradiol, progesterone, and testosterone were analyzed by chemiluminescence technique and compared with the healthy control group. Results: Increased serum hormone levels in women with acne vulgaris accounted for 29.7%, and hyperandrogenism accounted for 16.0% of cases. We found significant differences in testosterone levels (mean value, 55.67±25.56 versus 38.37±10.16 ng/dL, p<0.05) respectively, in the acne group and the control group. However, the estradiol level of the acne group (323.15±93.31 pmol/L) was lower than the control group (370.94±58.88 pmol/L), with p-value under 0.05. No statistically significant differences were found for progesterone (0.60±0.38 versus 0.50±0.15 ng/mL, p>0.05) levels. Moreover, we did not find the relationship between serum hormone levels and the severity of acne vulgaris. Conclusion: This study showed that female acne vulgaris patients may have high serum testosterone levels and low serum estradiol levels compared with those of female controls. However, hormone alterations had no correlation with acne severity.
Article
Acne is a common, worldwide problem that is usually multifactorial in etiology, but androgens may play a pivotal role in the development and severity of acne. Endocrinopathies, like polycystic ovarian syndrome, ovarian tumors, or adrenal hyperplasia or tumors may be detected in some patients with acne, especially if acne is sudden in onset, associated with hirsutism or menstrual irregularities, or associated with cushingoid facies, acanthosis nigricans, patterned hair loss, or deepened voice. In these instances, serum free and total testosterone, DHEAS, and LH, and FSH should be tested. Appropriate referral and long term follow up is warranted in patients diagnosed with an endocrinopathy. Hormonal therapies for acne include systemic medications with various mechanisms: androgen receptor blockers, adrenal androgen production blockers, or ovarian androgen production blockers. Androgen receptor blockers include spironolactone, cyproterone acetate, chlormadinone, and flutamide; adrenal androgen production blockers include glucocorticoids, and ovarian production blockers include gonadotropin-releasing agonists and oral contraceptives. Herein, practical guidelines are shared for the practicing physician treating hormonally related acne.
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MLN64 is a protein that is highly expressed in certain breast carcinomas. The C terminus of MLN64 shares significant homology with the steroidogenic acute regulatory protein (StAR), which plays a key role in steroid hormone biosynthesis by enhancing the intramitochondrial translocation of cholesterol to the cholesterol side-chain cleavage enzyme. We tested the ability of MLN64 to stimulate steroidogenesis by using COS-1 cells cotransfected with plasmids expressing the human cholesterol side-chain cleavage enzyme system and wild-type and mutant MLN64 proteins. Wild-type MLN64 increased pregnenolone secretion in this system 2-fold. The steroidogenic activity of MLN64 was found to reside in the C terminus of the protein, because constructs from which the C-terminal StAR homology domain was deleted had no steroidogenic activity. In contrast, removal of N-terminal sequences increased MLN64’s steroidogenesis-enhancing activity. MLN64 mRNA was found in many human tissues, including the placenta and brain, which synthesize steroid hormones but do not express StAR. Western blot analysis revealed the presence of lower molecular weight immunoreactive MLN64 species that contain the C-terminal sequences in human tissues. Homologs of both MLN64 and StAR were identified in Caenorhabditis elegans, indicating that the two proteins are ancient. Mutations that inactivate StAR were correlated with amino acid residues that are identical or similar among StAR and MLN64, indicating that conserved motifs are important for steroidogenic activity. We conclude that MLN64 stimulates steroidogenesis by virtue of its homology to StAR.
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Keratinocyte growth factor (KGF), a recently discovered 18.9 kD member of the fibroblast growth factor family has been shown to selectively induce keratinocyte proliferation and differentiation in tissue culture. To explore its potential stimulating keratinocyte growth and differentiation in vivo, we analyzed for the influence of KGF on epithelial derived elements within a wound created through the cartilage on the rabbit ear. KGF accelerated reepithelialization (p = 0.004) and increased the thickness of the epithelium (p = 0.0005) when 4-40 micrograms/cm2 recombinant KGF was added at the time of wounding. The regenerating epidermis showed normal differentiation as detected by cytokeratin immunostaining. Remarkably, however, KGF stimulated proliferation and differentiation of early progenitor cells within hair follicles and sebaceous glands in the wound bed and adjacent dermis. There was a transient but highly significant increase in specific labeling of cycling cells in both basal and suprabasal layers that extended into the spinous layer of the regenerating epidermis. As an indication of specificity, the inflammatory cells and fibroblasts within the wound were not influenced by KGF. The results indicate that KGF is unique in its ability to accelerate reepithelialization and dermal regeneration by targeting multiple epithelial elements within the skin. These results suggest that KGF may induce specific epithelial progenitor cell lineages within the skin to proliferate and differentiate, and thus may be a critical determinant of regeneration of skin. Furthermore, these findings illustrate the potential capacity of this system to analyze epithelial differentiation programs and disorders of epidermis, dermal glandular elements, and hair follicles.
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The growth and development of hair follicles is influenced by a number of different growth factors and cytokines, particularly members of the fibroblast growth factor (FGF) family. Keratinocyte growth factor (KGF or FGF-7) is a recently identified 28-kd member of the FGF family that induces proliferation of a wide variety of epithelial cells, including keratinocytes within the epidermis and dermal adnexa. Because KGF induces marked proliferation of keratinocytes, and both KGF and KGF receptor (KGFR) mRNA are expressed at high levels in skin, we sought to localize KGF and KGFR in skin by in situ hybridization. KGFR mRNA was relatively strongly expressed by keratinocytes in the basilar epidermis as well as throughout developing hair follicles of rat embryos and neonates. KGF mRNA was expressed at lower levels than was KGFR but could be localized to follicular dermal papillae in rat embryos and neonates. These results prompted us to investigate the effects of KGF on hair follicles in two distinct murine models of alopecia. In the first model, recombinant KGF (rKGF) induced dose-dependent hair growth over most of the body in nu/nu athymic nude mice when administered intraperitoneally or subcutaneously over 17 to 18 days. When administered subcutaneously, rKGF induced the most extensive hair growth at the sites of injection. Histologically, rKGF induced marked follicular and sebaceous gland hypertrophy, a normalization of the nu/nu follicular keratinization defect, and an increase in follicular keratinocyte proliferation as assessed by bromodeoxyuridine labeling. In the second model, a neonatal rat model of cytosine arabinoside chemotherapy-induced alopecia in which interleukin-1, epidermal growth factor, and acidic FGF have all demonstrated some degree of alopecia cytoprotection, rKGF induced a dose-dependent cytoprotective effect, abrogating as much as 50% of the alopecia in this model when administered beginning 1 day before the onset of chemotherapy. Taken together, these data suggest that KGF is an important endogenous mediator of normal hair follicle growth, development, and differentiation.
Article
Background This study examined the relationships of pubertal maturation and sex steroid hormones to the development of acne in young girls. Black (n=317) and white (n=306) premenarchal girls with a mean age of 9.97±0.62 years were evaluated for acne prevalence and severity, pubic hair and areolar maturation, and sex steroid hormone levels. Results Overall, 77.8% of the girls had some acne; of the whole group, 48.3% had only comedonal acne, 2.2% had only inflammatory acne, and 27.3% had both types. Although black girls matured at an earlier age than white girls, racial differences in acne were minimal when adjusted for pubertal maturation. Acne increased with advancing maturation; at Tanner pubic hair stages 1, 2, and 3, the prevalence of acne rose from 73.1% to 84.0% and to 90.6%, respectively. Acne lesion counts at seven facial locations revealed a predominance of midfacial acne on the middle aspect of the forehead, nose, and chin. Sex steroid hormone levels measured in 365 of the girls were found to increase significantly during maturation from prepuberty to early puberty. Testosterone-estrogen—binding globulin and the ratio of testosterone to estradiol decreased. In 118 prepubertal girls, estradiol, total and free testosterone, progesterone, testosterone to estradiol ratio, and testosterone-estrogen—bindingglobulin levels were no different whether in subjects with acne or without acne. However, the level of dehydroepiandrosterone sulfate, an androgen of adrenal origin, was significantly higher in prepubertal girls with acne. Conclusion Acne, especially the comedonal type, can be the first sign of pubertal maturation in girls, even preceding pubic hair and areolar development. Concentration of dehydroepiandrosterone sulfate is significantly and specifically associated with the initiation of acne in young girls.(Arch Dermatol. 1994;130:308-314)
Article
Objective: To identify and describe patients with hepatotoxicity possibly caused by flutamide, an antiandrogen drug. Design: Case series of reports, submitted to the Adverse Drug Event Reporting System of the Food and Drug Administration. Setting: Outpatient clinics and physicians' offices in the United States. Patients: Nineteen patients treated with flutamide for prostate cancer or benign prostatic hypertrophy (for Investigation of a New Drug or off-label use). Measurements: Evidence of increased liver enzyme levels, hyperbilirubinemia, associated clinical symptoms, and diagnoses of cholestatic hepatitis. Autopsy reports were used when available
Article
• Background and Design.— Increases in sebaceous gland activity are often the earliest sign of the approach of puberty in children. These increases have been attributed to increases in the secretion of adrenal androgens, but the supporting data are sparse and are based on measurements of urinary, rather than serum, androgen concentrations. In this study, we examined sebum composition, serum levels of dehydroepiandrosterone sulfate, and pubertal stage in 111 boys and girls, aged 2 to 15 years. Sebum composition was evaluated by measuring the ratio of wax esters/(cholesterol + cholesterol esters), a ratio known to increase with increasing sebaceous gland activity. Results.— Both wax esters/(cholesterol + cholesterol esters) ratios and serum dehydroepiandrosterone sulfate levels began to increase in children 7 to 10 years old. These changes occurred in many children before the appearance of any physical signs of puberty. Wax esters/(cholesterol + cholesterol esters) ratios were correlated with dehydroepiandrosterone sulfate levels in both boys and girls. In prepubertal children, the regression lines passed through the origin. In subjects who were in early or late puberty, the y intercepts of the regression lines had positive values. Conclusion.— Adrenal androgens appear to be the major determinants of sebaceous gland activity during the prepubertal period and to be additive to another hormone or hormones during puberty.(Arch Dermatol. 1992;128:1345-1348)
Article
The presence of 5α-reductase (5α-R) in skin may indicate that the androgen regulation of sebaceous glands and sebum production requires the local conversion of testosterone to dihydrotestosterone. The goals of this study were to identify which isozyme of 5α-R (type 1 or type 2) is expressed in sebaceous glands from facial areas, scalp, and non-acne-prone areas; to determine if 5α-R activity is concentrated in sebaceous glands; to assess whether there are regional differences in this enzyme's activity; and to test the effects of azasteroid inhibitors and 13-cis retinoic acid on 5α-R in these tissues. Sebaceous glands were microdissected from facial skin, scalp, and non-acne-prone skin (arm, breast, abdomen, leg), and the activity of 5α-R was determined. A total of 49 samples from 23 male and 21 female subjects without acne (age range, 16 to 81 years, 56 ± 20 years [mean ± SD]) was analyzed. The biochemical properties of the enzyme in each of the samples tested are consistent with those of the type 1 5α-R. Minimal to no type 2 5α-R was detected. The level of 5α-R activity was significantly higher in the sebaceous glands compared to whole skin in facial skin (p = 0.047), scalp (p = 0.039), and non-acne-prone skin (p = 0.04). Enzyme activity in sebaceous glands from facial skin and scalp was significantly higher than in a comparable amount of sebaceous gland material obtained from non-acne-prone areas (32 ± 6 [mean ± SEM]), 35 ± 7 (mean ± SEM) versus 6.0 ± 3.0 (mean ± SEM) pmol/min/mg protein, p = 0.014 and 0.007, respectively). Finasteride and 13-cis retinoic acid were poor inhibitors of the enzyme with 50% inhibitory concentration values greater than 500 nM. These data demonstrate that in the skin from older patients without acne the type 1 isozyme of 5α-R predominates, its activity is concentrated in sebaceous glands and is significantly higher in sebaceous glands from the face and scalp compared to non-acne-prone areas, and the action of 13-cis retinoic acid in the control of acne is not at the level of 5α-R. Furthermore, we suggest that specific inhibition of the type 1 5α-R may offer a viable approach to the management of sebum production and, hence, acne.
Article
Purpose: To assess the efficacy and safety of a low-dose oral contraceptive (OC) containing norethindrone acetate (NA) and ethinyl estradiol (EE) (Estrostep; Parke-Davis, Morris Plains, NJ) compared with placebo in the treatment of moderate acne vulgaris, and the impact of treatment on quality of life. Methods: A total of 593 women ranging in age from 14 to 49 years were enrolled in 2 identical, randomized, double-blind, placebo-controlled, parallel-group, multicenter studies over six 28-day cycles. Two hundred ninety-seven subjects received NA/EE (1 mg NA/20 μg EE for 5 days, 1 mg NA/30 μg EE for 7 days, and 1 mg NA/35 μg EE for 9 days), and 296 received placebo. Efficacy for primary end points was determined by changes in acne lesion counts and an investigator's facial acne global assessment (FAGA). In addition, differences in mean scores of 4 domains of an acne-specific quality-of-life questionnaire (Acne-QoL) were examined. Results: Estrostep-treated subjects showed a significantly greater decrease from baseline in lesion counts at study exit, including inflammatory lesions (P = .0014), comedones (P = .0003), and total acne lesions (P < .0001) relative to placebo. A significantly greater proportion of Estrostep-treated subjects had investigator ratings on the FAGA of absent, minimal, or mild compared with placebo (P = .0004) at the end of the study. In addition, Estrostep-treated subjects had significant improvements in Acne-QoL ratings versus placebo, with improvements in all 4 domains: self perception, role-emotional, role-social, and acne symptoms (all P < .0001). Conclusions: As measured by both lesion counts and a rigorous investigator assessment, Estrostep was efficacious in the treatment of moderate acne vulgaris. Finally, acne treatment with Estrostep resulted in a significant improvement in health-related quality of life.
Article
Sebaceous glands were isolated by manual dissection using a stereomicroscope from skin specimens of bald scalp of men with male-pattern baldness undergoing hair transplant or scalp reduction surgery and also from specimens taken from hairy and bald areas of scalp at autopsy of adult male victims of accidental death within 3 h post mortem. Homogenates of the isolated glands exhibited activities of Δ5-3β-hydroxysteroid dehydrogenase (3βHSD), 17β-hydroxysteroid dehydrogenase and testosterone 5α-reductase by the conversion of [3H]dehydroepiandrosterone (DHA) to 3H-Δ4-androstenedione (AD), [3H]testosterone, and [3H]dihydrotestosterone. Homogenates of glands from bald (B) scalp had greater 3βHSD activity than homogenates of glands from hairy (H) scalp. After differential centrifugation, 3βHSD activity was found mainly in the microsomal and 105,000 × g supernatant fractions. Specific activity of the enzyme based on protein mass was highest in the microsomal fraction; however, the total 3βHSD activity in the 105,000 × g supernatent of B glands was significantly (p < .01) greater than that of H glands. 3βHSD activity in sebaceous glands isolated from autopsy specimens did not differ from that of glands isolated from surgical specimens in apparent Km(0.13- 0.14 μM), pH optima (8.0), or coenzyme requirement for NAD. Since substantial 3βHSD activity was present in the cytosol, and cytosol of B glands showed increased 3βHSD activity, the increased conversion of DHA to AD may be a critical step for androgenic action and may be responsible for excessive androgenicity in male-pattern baldness.
Article
High doses of flutamide, which is the only antiandrogen that specifically blocks the androgen receptor, have recently been used with good clinical results in women with hirsutism. Since regression of hair growth requires long-term therapy, clinical and economic considerations are important. The use of the lowest efficacious dosage could reduce costs. This study was undertaken to compare safety and efficacy of a low dose of flutamide (125 mg twice daily) alone and in combination with a triphasic oral contraceptive (OC) in women with idiopathic hirsutism. Flutamide was administered orally in a low dose of 125 mg twice daily for 12 months alone in women with no risk of pregnancy or during the use of an oral contraceptive. Women were seen every 3 months and were evaluated for hirsutism score, hormone and lipid measurements. The study, which was conducted as a prospective open trial, was proposed to patients with idiopathic hirsutism, that is, with serum androgen levels in normal range and LH/FSH ratio less than 2. A statistically significant decrease in hirsutism score as compared to baseline was observed after only 3 months with either treatment, flutamide alone (16.9 +/- 1.6 vs 14.2 +/- 1.7, P < 0.0001) or the combination of flutamide with OC (15.6 +/- 0.8 vs 11.9 +/- 0.8, P < 0.001). Three months after cessation of treatment a statistically significant decrease from baseline was observed in the two groups. Nevertheless, at 6 months post-treatment this decrease was still significant only in the group who took flutamide in combination with an oral contraceptive. Flutamide alone does not appear to modify the levels of lipoproteins. The association of flutamide with a triphasic formulation significantly increased the HDL-C levels. This study shows beneficial effects of a low dose of flutamide in women with idiopathic hirsutism. The addition of an oral contraceptive is judicious to prevent pregnancy and reduce recurrence of hirsutism after cessation of flutamide. Peripheral androgenic blockage does not modify lipid profiles and it might reduce the negative effect of oral contraceptive on HDL-C levels. The addition of electrolysis delays the recurrence of hirsutism after cessation of flutamide.
Article
The enzyme steroid 5 alpha-reductase catalyzes the conversion of testosterone into the more potent androgen, dihydrotestosterone, and impairment of this reaction causes a form of male pseudohermaphroditism in which genetic males differentiate predominantly as phenotypic females. We previously isolated cDNA clones that encode a human steroid 5 alpha-reductase enzyme. Here, we report molecular and genetic studies demonstrating that the gene encoding this cDNA is normal in subjects with the genetic disease steroid 5 alpha-reductase deficiency. We further show that in contrast to the major steroid 5 alpha-reductase in the prostate and cultured skin fibroblasts, the cDNA-encoded enzyme exhibits a neutral to basic pH optima and is much less sensitive to inhibition by the 4-aza steroid, finasteride (MK-906). The results provide genetic, biochemical, and pharmacological support for the existence of at least two steroid 5 alpha-reductase isozymes in man.
Article
Rat preputial cells were grown in an epithelial cell primary monolayer culture system identical to that used for culturing epidermal cells, which were studied for comparison. Despite similar appearance when observed by phase contrast microscopy, other features identified the preputial cells as a unique epithelial cell population. Preputial cells grew as a relatively small number of large colonies, formed domes before confluence, and expressed a specific acinar keratin, K4, which had previously been found in human sebaceous glands. In addition, preputial cells formed fewer cornified envelopes than epidermal cells, too few to discern the reduction of envelope formation by retinoic acid treatment in vitro which was found in epidermal cells. Rat preputial cells in monolayer culture, therefore, are a promising model for studying the effects of hormones on sebaceous cell growth and differentiation.
Article
Increases in sebaceous gland activity are often the earliest sign of the approach of puberty in children. These increases have been attributed to increases in the secretion of adrenal androgens, but the supporting data are sparse and are based on measurements of urinary, rather than serum, androgen concentrations. In this study, we examined sebum composition, serum levels of dehydroepiandrosterone sulfate, and pubertal stage in 111 boys and girls, aged 2 to 15 years. Sebum composition was evaluated by measuring the ratio of wax esters/(cholesterol + cholesterol esters), a ratio known to increase with increasing sebaceous gland activity. Both wax esters/(cholesterol + cholesterol esters) ratios and serum dehydroepiandrosterone sulfate levels began to increase in children 7 to 10 years old. These changes occurred in many children before the appearance of any physical signs of puberty. Wax esters/(cholesterol + cholesterol esters) ratios were correlated with dehydroepiandrosterone sulfate levels in both boys and girls. In prepubertal children, the regression lines passed through the origin. In subjects who were in early or late puberty, the y intercepts of the regression lines had positive values. Adrenal androgens appear to be the major determinants of sebaceous gland activity during the prepubertal period and to be additive to another hormone or hormones during puberty.
Article
We showed previously that the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, the rate-limiting enzyme of cholesterol biosynthesis, increases after both barrier disruption with organic solvents and in essential fatty acid deficiency (EFAD). Here, we treated EFAD hairless mice with linoleic acid, columbinic acid (C18: 3, n-6, trans; not metabolizable to known regulatory eicosanoids), prostaglandin E2 (PGE2), or latex occlusion, and determined transepidermal water loss (TEWL), epidermal protein content, and epidermal HMG CoA reductase activity. Increased TEWL rates in EFAD were accompanied by increased HMG CoA reductase activity (+130%, n = 6, p less than 0.01) and protein content (+69%; n = 6, p less than 0.025). Artificial restoration of the barrier by occlusion reduced the increase in enzyme activity and protein content toward normal, but barrier function, measured immediately after removal of the latex wrap, deteriorated further (TEWL: two-fold greater than EFAD unoccluded; p less than 0.01). Topical applications of either linoleate or columbinate (but not PGE2), normalized barrier function, HMG CoA reductase activity, and protein content. These results show that a) barrier function modulates HMG CoA reductase activity; b) reduction of cholesterol synthesis with occlusion results in a further deterioration in barrier function, suggesting that increased synthesis is a protective homeostatic response; and c) the barrier abnormality reflects a requirement for specific fatty acids for the barrier rather than resulting from epidermal hyperplasia or decreased prostaglandin generation.
Article
In the treatment of androgen-mediated skin disorders spironolactone provides a valuable therapeutic option. This article reviews the use of spironolactone as an antiandrogen in dermatologic therapy. The endocrinologic effects, pharmacology, dermatologic uses, and side effects are discussed, and guidelines for its use are provided.
Article
The effect of a low dose triphasic oral contraceptive (OC) was evaluated during a 6-month treatment period in 41 patients (mean age, 25.4 +/- 0.7 yr) who had grade I-IV postpubertal acne and normal menses. The OC contained three dose levels of ethynyl estradiol and dl-norgestrel. Acne lesions were assessed, and serum androgen levels were measured during a control cycle and between days 17-21 of treatment cycles 1, 2, 3, and 6. Four patients dropped out after 3 months of treatment. Acne was significantly improved after the first OC cycle. After six cycles, the number of comedones had decreased by 79.6 +/- 3.2% (range, 50-100%) in 69.4% of the patients. Mean baseline levels of testosterone, 17-hydroxyprogesterone, and dehydroepiandrosterone sulfate were in the upper third of the normal range, with elevated individual values in 18.9%, 36.5%, and 26.8% of the women, respectively. Mean baseline levels of androstenedione, free testosterone (T), and 3 alpha-androstanediol glucuronide (3 alpha-diol-G) were above the normal range, with elevated individual values in 51.2%, 75.0%, and 85.4% of the patients, respectively. Sex hormone-binding globulin (SHBG) levels were below the normal range in 26.8% of the cases. At the end of the first OC cycle, there was a significant (P less than 0.01) decrease in all androgen precursors and a 2-fold increase in SHBG. Androstenedione and free T decreased into the normal range during OC intake. Serum 3 alpha-diol-G levels remained elevated, but had decreased by 34.5% at cycle 6 (P less than 0.05). These results show that the triphasic OC has significantly improved acne in postpubertal women for whom acne was the main manifestation of mild hyperandrogenic activity. The improvement in acne corresponded to a decrease in adrenal/ovarian androgens and free T, which led to a decreased metabolism to 3 alpha-diol-G, presumably by the sebaceous glands. The increase in SHBG is considered an estrogenic effect, and the triphasic formulation containing low dose dl-norgestrel is not androgenic but, rather, an estrogen-dominant formulation; as such, this product is recommended in women requiring contraception who also have idiopathic acne.
Article
Polycystic ovarian syndrome (PCOS) appears to be due to a previously unrecognized type of steroidogenic abnormality, one in which hyperandrogenism arises from a regulatory abnormality (dysregulation) rather than from enzyme deficiency. It appears that PCOS typically arises from masculinized regulation of the androgen-forming enzyme (cytochrome P450c17 alpha) within ovarian thecal cells. This may arise by either excessive stimulation by luteinizing hormone (LH) or by escape from desensitization to LH. We review evidence which is compatible with the concept that the latter situation may result from an intrinsic intraovarian flaw in the paracrine feedback mechanism by which thecal androgen biosynthesis is inhibited and that coexistent adrenal 17-ketosteroid hyper-responsiveness to corticotropin (ACTH) may be due to a similar type of dysregulation of adrenocortical P450c17 alpha.
Article
Since the recent introduction of a drug regimen containing 2 mg of the antiandrogen cyproterone acetate and 50 micrograms ethinyl-oestradiol (Diane; oestrogen-cyproterone acetate) several uncontrolled reports have extolled the benefits of this drug. Double blind studies, however, are lacking. Sixty two patients with moderate or moderately severe acne were therefore included in a double blind trial of treatment for six months comparing tetracycline alone, oestrogen-cyproterone acetate alone, and a combination of these agents. Sebum excretion rates and bacterial counts were measured before, during, and after treatment, at the same time as a clinical assessment was made. At six months the acne (as assessed by overall grade) had improved by 68% in the antibiotic treated group and by 74% in the oestrogen-cyproterone treated group. The group given a combination of both agents improved by 82%, which was significantly better (p less than 0.025) than the improvement in the tetracycline treated patients. No significant difference was found between the groups given oestrogen-cyproterone alone and the combined treatment. The sebum excretion rate was suppressed by 25% in the patients in both groups receiving oestrogen-cyproterone but not in the group given antibiotics alone. Oestrogen-cyproterone acetate is as effective as antibiotics in treating acne in women, and adding antibiotics offers no advantage over using oestrogen-cyproterone on its own, although in this study the combination was more effective than tetracycline alone at six months.
Article
The effect of high-dose cyproterone acetate-ethinyl estradiol treatment on rates of sebum secretion and on the proportions of linoleic acid (18:2 delta 9,12) and sebaleic acid (18:2 delta 5,8) in the skin surface lipids of three female acne patients was examined. Changes in rates of sebum secretion were evaluated indirectly by measuring the ratio of wax esters/(cholesterol + cholesterol esters) in the subjects' skin surface lipid. In two of the subjects, this ratio indicated a reduction of sebum secretion rates to the childhood range. Concomitantly, there was an increase in linoleic acid and a decrease in sebaleic acid in all lipid classes. In the third subject, in whom there was only a small reduction in sebum secretion rate, the proportion of linoleic acid in the cholesterol esters more than doubled, but the changes in the other lipid classes were small or nonexistent. The results indicate that the proportions of linoleic acid and sebaleic acid in sebum are influenced by sebum secretion rates.
Article
Lipogenesis in isolated human sebaceous glands from [U-14C]glucose, [U-14C]leucine, [U-14C]isoleucine, and [U-14C]valine has been determined by thin-layer chromatography. Total lipogenesis from 2 mmol/l [U-14C]glucose was 114.8 +/- 22.3 pmol/gland per h (mean +/- SE), with 53.8% being incorporated into triglycerides, 20.2% into squalene, 12.8% into phospholipids, 2.1% into cholesterol and 7.1% into wax monoester and cholesterol ester and 5% into di- and monoglycerides and free fatty acids. Total lipogenesis from 2 mmol/l [U-14C]leucine, 2 mmol/l [U-14C]isoleucine, and 2 mmol/l [U-14C]valine in the presence of 2 mmol/l glucose was 26, 29 and 9%, respectively, of that seen with 2 mmol/l glucose alone. The pattern of 14C distribution in the various lipid classes from the three U-14C-labelled branched-chain amino acids was not significantly different from that seen with [U-14C]glucose.
Article
We measured hormone levels in 59 women and 32 men with longstanding cystic acne resistant to conventional therapy. Affected women had higher serum levels of dehydroepiandrosterone sulfate, testosterone, and luteinizing hormone and lower levels of sex-hormone-binding globulin than controls. Affected men had higher levels of serum dehydroepiandrosterone sulfate and 17-hydroxyprogesterone and lower levels of sex-hormone-binding globulin than controls. To lower dehydroepiandrosterone sulfate, dexamethasone was given to men, and dexamethasone or an oral contraceptive pill, Demulen (or both), was given to women. Of the patients treated for six months, 97 per cent of the women and 81 per cent of the men had resolution or marked improvement in their acne. The dose of dexamethasone required to reduce dehydroepiandrosterone sulfate levels was low, rarely exceeding the equivalent of 20 mg of hydrocortisone per day. We conclude that most patients with therapeutically resistant cystic acne have androgen excess and that lowering elevated dehydroepiandrosterone sulfate results in improvement or remission of acne in most instances.
Article
We have studied a group of young adult women of mean age 23.8 +/- 6.5 (SD) years with only acne (A, n = 46), only hirsutism (H, n = 10), and acne plus hirsutism (A + H, n = 19) who sought dermatologic care. We measured the androgens, total and free testosterone (T), free 17 beta-hydroxysteroids (17-beta), dehydroepiandrosterone sulfate (DS), and the androgen precursors 17 alpha-hydroxypregnenolone (17-Preg) and 17 alpha-hydroxyprogesterone (17-Prog), as well as testosterone-estrogen binding globulin in all patients. Plasma hormone levels of the patients were compared to those of 23 controls of mean age 25.6 +/- 6.6 years who had neither acne nor hirsutism. Mean levels of all hormones measured, except 17-Preg, were elevated in the women with acne. Fifty-two percent of Group A, 60% of Group H, and 63% of Group A + H patients had at least one abnormal hormone level. The most frequently elevated plasma androgens in all the women with acne were: free T 25%, free 17-beta 23%, and DS 19%. Total T was high in only 12%. Elevations of plasma androgens were present in some women who did not have hirsutism or irregular menses. Identification of endocrine abnormalities in women with acne may potentially offer an opportunity for hormonal therapy.
Article
3 beta-hydroxysteroid dehydrogenase delta 4-5-isomerase (delta 5-3 beta-HSD) catalyzes an early step in the synthesis of testosterone from dehydroepiandrosterone (DHA). We compared enzyme activity in back skin biopsies with sebum excretion rate (SER) in 14 individuals. The rate of conversion of [7 alpha-3H]DHA into [3H]-4-androstene-3,17-dione was measured in cryostat sections of skin and compared with the sebaceous gland content of the same biopsies. Reaction rate was proportional to the volume of sebaceous gland tissue in the sections. Enzyme activity was absent from sections without histologically identifiable sebaceous gland tissue. This suggests that the delta 5-3 beta-HSD is localized in sebaceous glands. SER, measured by a modified photometric technique at the biopsy site, correlated highly with sebaceous gland volume and with the rate of conversion of DHA into androstenedione in the biopsy. For each biopsy, specific activity of delta 5-3 beta-HSD in sebaceous glands was calculated by dividing the rate of formation of [3H]-4-androstene-3,17-dione by sebaceous gland volume. Specific activity of delta 5-3 beta-HSD did not correlate significantly with SER, suggesting that variations in concentration of delta 5-3 beta-HSD in sebaceous glands probably do not underlie variations in sebaceous gland activity.
Article
Human forehead skin incubated in vitro is known to metabolize testosterone to 17-oxosteroids faster than the reverse reaction, while axillary skin rapidly metabolizes androstenedione to 17 beta-hydroxysteroids, such as testosterone and 5 alpha-dihydrotestosterone. While this has been confirmed using a larger number of patients, some indication has been found that 17 beta-hydroxysteroid oxidoreductase activity declines with age in the axilla. The relative rates of 17 beta-oxidation and reduction (direction of operation of skin 17 beta-hydroxysteroid oxidoreductase activity) were not altered by variety of incubation conditions. Large amounts of a membrane-bound 17 beta-hydroxysteroid oxidoreductase, showing preference for NAD as coenzyme and testosterone (rather than androstenedione) as steroid substrate, were found in forehead skin from one patient. On the other hand, the main axillary skin enzyme in skin from another patient was soluble and showed preference for NADP and androstenedione. It is postulated that 17 beta-oxidation and reduction in skin is controlled by the relative amount, the coenzyme preferences and the kinetic properties of these two enzymes.
Article
Steroidogenic acute regulatory protein (StAR) plays a key role in steroid hormone synthesis by enhancing the metabolism of cholesterol into pregnenolone. We determined the organization of the StAR structural gene, mapped to 8p11.2. The gene spans 8 kb and consists of seven exons interrupted by six introns. The 1.3 kb of DNA upstream from the transcription start site directed expression of a luciferase reporter gene in mouse Y-1 adrenal cortical tumor cells but not in BeWo choriocarcinoma cells. Reporter gene expression in the Y-1 cells was increased more than 2-fold by 8-Br-cAMP, indicating that the 1.3 kb DNA fragment contains sequences that confer tissue-specific expression and cAMP regulation. The sequence of a related StAR pseudogene, mapped to chromosome 13, lacks introns and has an insertion, numerous substitutions, and deletions. Expression of StAR in COS-1 cells cotransfected with cholesterol 27-hydroxylase (P450c27) and adrenodoxin resulted in a 6-fold increase in formation of 3 beta-hydroxy-5-cholestenoic acid, demonstrating that StAR's actions are not specific to steroidogenesis but extend to other mitochondrial cholesterol-metabolizing enzymes.
Article
Evidence is provided that human skin, the largest body organ exposed to multiple stressors, expresses proopiomelanocortin (POMC), corticotropin releasing hormone (CRH) and CRH-receptor (CRHR) genes in vivo. In vitro studies show that POMC and CRHR mRNAs are transcribed in melanocytes, cells derived from the neural crest, and in keratinocytes, cells derived from the ectoderm. CRH mRNA is transcribed in cultured melanocytes but not in keratinocytes. It is proposed that an equivalent of the 'hypothalamus-pituitary axis' composed of the CRH-CRHR-POMC loop is conserved in mammalian skin.
Article
To identify and describe patients with hepatotoxicity possibly caused by flutamide, an antiandrogen drug. Case series of reports, submitted to the Adverse Drug Event Reporting System of the Food and Drug Administration. Outpatient clinics and physicians' offices in the United States. Nineteen patients treated with flutamide for prostate cancer or benign prostatic hypertrophy (for Investigation of a New Drug or off-label use). Evidence of increased liver enzyme levels, hyperbilirubinemia, associated clinical symptoms, and diagnoses of cholestatic hepatitis. Autopsy reports were used when available. From the time of marketing of flutamide in February 1989 through March 1991, the Food and Drug Administration received reports of 19 patients in the United States who developed serious hepatotoxicity while using flutamide. Fourteen patients had resolution of abnormal liver function test results after discontinuing or decreasing the dose of flutamide, but five patients died of progressive liver disease. Autopsy reports from three patients and abnormal pathologic results from three other patients (reported to the Food and Drug Administration or in the medical literature) showed hepatocellular necrosis and possibly cholestasis. Thorough work-ups excluded other possible causes than flutamide. Flutamide appears to cause hepatotoxic effects in certain patients. Physicians should tell patients to immediately report to physicians nausea, vomiting, fatigue, jaundice, and other signs and symptoms of liver injury.
Article
Androgen receptors were localized in cryostat sections of human skin using monoclonal antibodies to the human androgen receptor. Bound antibodies were detected using biotinylated rabbit anti-rat IgG, peroxidase-conjugated streptavidin, and diaminobenzidine as chromogen. In the neonatal foreskin, antibody to androgen receptor bound to keratinocytes in the epidermis and to fibroblasts and vascular endothelial cells in the dermis. Immunohistochemical staining was stronger in nuclei than in cytoplasm. This staining was specific, because there was no significant staining when antibody to the androgen receptor was replaced with IgG from nonimmunized rats or with buffer, or when antibody to androgen receptor was incubated, prior to immunostaining, with a trp E-human androgen-receptor fusion protein used as immunogen. Incubation of androgen receptor antibody with trp E alone did not affect staining. Androgen-receptor antibody also bound to keratinocytes, fibroblasts, and endothelial cells in skin from adult men and women. Skin from the scalp, nose, lip, back, and chest gave positive staining for androgen receptor. Antibody to androgen receptor also bound to the coil and ductal cells of eccrine glands, external root sheath of hair follicles, epithelium in the hair bulb, dermal papilla cells, and sebocytes. There was no significant binding to adipocytes, collagen, or stratum corneum. These results show that androgen receptor is present in cells that are known to be targets for androgens and also in cells in which the biologic effects of androgens are yet to be characterized.
Article
The growth and development of pilosebaceous units in their characteristic pattern depends on the interaction of androgens and diverse biologic factors. Stromal-epithelial interactions are essential features. Considerable evidence suggests that androgens stimulate the growth of sensitive pilosebaceous units primarily by acting on specific stromal cells and that androgens and retinoic acid interact to regulate specific stages of sebocyte differentiation.
In addition to the classical steroidogenic tissues, namely the ovaries, testes, adrenals and placenta, a large series of human peripheral tissues possess all the enzymatic systems required for the formation of active androgens and oestrogens from a relatively large supply of precursor steroids provided by the adrenals. This chapter describes the structure, function, tissue-specific expression and regulation of the 3 beta-HSD and 17 beta-HSD gene families as well as some information about the aromatase gene. While, so far, most therapeutic approaches have been aimed and limited at controlling steroid formation by the classical steroidogenic tissues, it is clear that major efforts should now be turned towards intracrinology in order to understand better the physiological mechanisms controlling local steroid formation in peripheral target tissues and thus be in a position to develop novel therapeutic approaches that take into account the high proportion of steroids that are made locally and are responsible for the growth and function of normal as well as cancerous tissue.
Article
To evaluate the androgen control of sebum, subjects with complete androgen insensitivity and male pseudohermaphrodites with inherited 5 alpha-reductase deficiency and decreased dihydrotestosterone (DHT) production had sebum production studied. A hydrophobic polymeric film applied to the forehead was used to measure sebum production through the use of air filled micropores. Sebum scores of normal preadrenarchal children (ages 2-6), and normal age-matched adult males and females, were studied as well as males treated with the 5 alpha-reductase inhibitor, finasteride, for benign prostatic hyperplasia who were studied at baseline and after drug therapy. Androgen insensitive subjects had no sebum production by this methodology, and the results were identical to preadrenarchal children. In contrast, adult male pseudohermaphrodites with 5 alpha-reductase deficiency and a selective decrease in DHT production had sebum production scores identical to normal age-matched males. Males with benign prostatic hyperplasia treated with the 5 alpha-reductase inhibitor, finasteride, to lower DHT levels did not decrease the sebum score from baseline values. The lack of demonstrable sebum in androgen-insensitive subjects clearly demonstrates the absolute androgen control of sebum production. The DHT dependency of the sebaceous gland, however, could not be demonstrated in this study. Two 5 alpha-reductase isoenzymes 1 and 2, have been described. 5 alpha-reductase-2 is the gene responsible for inherited 5 alpha-reductase deficiency. Although the degree of inhibition of DHT in utero and in adulthood in male pseudohermaphrodites with a defect in 5 alpha-reductase-2 enzyme activity caused severe impairment of external genital and prostate differentiation and decreased facial and body hair, it had no demonstrable effect on sebaceous gland development or function. Furthermore, lowering DHT levels in adulthood had no effect on sebum production. If the gland is rich in the enzyme 5 alpha-reductase-2, it is proposed that the sebaceous gland is either exquisitely sensitive to DHT, requiring only small amounts for normal development and function, or that male levels of testosterone compensate for DHT and maintain normal sebaceous gland activity throughout life. It is also possible that 5 alpha-reductase-1 is the enzyme of the sebaceous gland and is unaffected in the inherited condition and by finasteride.
Article
The conversion of cholesterol to pregnenolone, the rate-limiting step in steroid hormone synthesis, occurs on mitochondrial cytochrome P450scc, which catalyzes this reaction by receiving electrons from NADPH via a flavoprotein [adrenodoxin reductase (AdRed)] and an iron sulfur protein [adrenodoxin (Adx)]. The behavior of the genes and mRNAs encoding these proteins has been studied in several systems, but little is known about the behavior of the human proteins. Using cloned cDNAs for human P450scc and AdRed, we constructed bacterial expression vectors to make milligram quantities of the corresponding proteins. These, plus purified human Adx similarly prepared by Dr. L. Vickery, were injected into rabbits to raise antiserum to each of the proteins. Each antiserum was highly specific and did not cross-react with other mitochondrial proteins detectable by Western blotting. Human JEG-3 choriocarcinoma cells and mouse Y-1 adrenocortical carcinoma cells were then incubated for 0-24 h with 1 mM 8-bromo-cAMP (8Br-cAMP) or 30 nM phorbol 12-myristate 13-acetate (PMA; phorbol ester) plus 1 microM A23187 (calcium ionophore) to activate the protein kinase-A and -C pathways, respectively. In JEG-3 cells, 8Br-cAMP increased and PMA/A23187 slightly decreased the abundance of P450scc and Adx, but neither treatment had a detectable effect on AdRed. The production of pregnenolone by these cells increased 3-fold in response to 8Br-cAMP and fell to one third in response to PMA/A23187. In Y-1 cells, 8Br-cAMP increased the abundance of all three proteins, while PMA/A23187 decreased the abundance of P450scc and Adx. The production of pregnenolone by these cells increased 9-fold in response to 8Br-cAMP and was unaffected by TPA/A23187. These studies show that the three proteins of the cholesterol side-chain cleavage system behave in response to 8Br-cAMP and PMA/A23187 as predicted from the study of their genes and mRNAs, indicating that the chronic regulation of steroidogenesis in these cell systems is regulated principally at the level of mRNA abundance.
Article
Ligand-mediated activation of the insulin-like growth factor 1 (IGF-1) receptor is critical for epidermal keratinocyte proliferation in vitro, and its expression in normal and psoriatic epidermis suggests that it might regulate keratinocyte proliferation in vivo. In this study, we used a monoclonal antibody (alpha-IR3) that binds to the alpha-chain of this receptor to study its expression (i) in other epithelial cell types in human skin and (ii) in growth-activated epidermis associated with various cutaneous pathologies. In normal skin, IGF-1 receptors were expressed by basal epidermal keratinocytes as well as by basal-like or undifferentiated germinative epithelial cells associated with the follicular outer root sheath, sebaceous glands, and the hair matrix. There was minimal IGF-1 receptor expression in differentiating outer root sheath, hair shaft, and sebaceous epithelial cells. IGF-1 receptor expression in non-growth-activated epidermis of long-standing seborrheic keratoses was confined to the basal epidermal layer, as in normal epidermis. In contrast, hyperplastic epidermis undergoing "regenerative" differentiation (keratin 16+, Ki67+ suprabasal keratinocytes) from psoriasis, chronic skin wounds, and plaques of mycosis fungoides consistently showed increased expression of IGF-1 receptor. In these conditions, the region of expanded IGF-1 receptor expression delimited the epidermal zone of keratinocyte proliferation. In cultured keratinocytes, the subcellular localization of the IGF-1 receptor could be modulated from plasma membranes to the cell cytoplasm by ligand binding, suggesting that the in vivo cytoplasmic staining occasionally observed represents internalization of receptors following ligand stimulation. Our results suggest that cell surface IGF-1 receptors are widely expressed by epithelial cells with proliferative potential, that receptor expression can be modulated with differing epidermal growth states, and that these receptors are largely downregulated in highly differentiated epithelial cells.
Article
17 beta-Hydroxysteroid dehydrogenases (17 beta-HSDs) are enzymes involved in both the activation and inactivation of androgens and estrogens. 17 beta-HSD type 1 shows a high specificity for C18 steroids and is the major isozyme in the granulosa cells of the ovary. Its role is to convert the inactive C18 steroid estrone to the active estrogen estradiol, which in turn locally promotes maturation of the follicle. In contrast, attenuation of estradiol action in the glandular epithelium of the secretory endometrium is achieved by expression of the oxidative type 2 isozyme that inactivates estradiol to estrone. An interesting feature of 17 beta-HSD type 2 is that the enzyme also possesses 20 alpha-HSD activity, i.e., it catalyzes the 20 alpha-oxidation of the inactive C21 steroid 20 alpha-dihydroprogesterone to the active progestin progesterone. As the type 2 enzyme is also active on androgens, it may play a general role in the peripheral inactivation of androgens and estrogens, thus determining their steady-state levels in target tissues. The reductive 17 beta-HSD type 3 is predominantly expressed in the testis and converts the inactive C19 steroid androstenedione to the active androgen testosterone. The importance of the type 3 enzyme in male steroid hormone physiology is underscored by the genetic disease 17 beta-HSD deficiency. Mutations in the 17 beta-HSD3 gene impair the formation of testosterone in the fetal testis and give rise to genetic males with normal male Wolffian duct structures but female external genitalia. To date, 15 mutations have been identified in 18 subjects with the disease.
Article
To evaluate the efficacy of a triphasic, combination oral contraceptive (OC), (norgestimate-ethinyl estradiol), in comparison with placebo in the treatment of moderate acne vulgaris. Two hundred fifty women were enrolled in a multicenter, randomized, double-blind, placebo-controlled clinical trial to evaluate the effectiveness of norgestimate-ethinyl estradiol in the treatment of acne vulgaris. Subjects were 15-49 years old and had moderate acne vulgaris. Each month for 6 months, subjects received either 3 consecutive weeks of active OC treatment followed by 1 week of inactive drug, or 4 consecutive weeks of color-matched placebo tablets. Efficacy was assessed by facial acne lesion counts, the investigator's global assessment, and the subject's self-assessment. Hormone levels were also measured. Despite the large placebo effect inherent in an acne trial (due to, for example, careful skin care, frequent office visits, regression to the mean), of the 164 subjects who completed the study without major protocol deviations, the OC group was significantly better than the placebo group for all primary efficacy measures: inflammatory lesions (mean reduction, 51.4% compared to 34.6%; P = .01), total lesions (mean reduction, 46.4% compared to 33.9%; P = .001); investigator's global assessment (83.3% compared to 62.5%; P = .001). Free testosterone decreased significantly and sex hormone-binding globulin increased significantly in the OC group, but remained unchanged in the placebo group. A triphasic combination of norgestimate and ethinyl estradiol is an effective treatment for moderate acne vulgaris in women with no known contraindication to OC therapy.
Article
Acne vulgaris, or acne, as it is generally called, is the most common skin disease, affecting nearly 80 percent of persons at some time between the ages of 11 and 30 years.1 It can persist for years and result in disfigurement and permanent scarring, and it can have serious adverse effects on psychosocial development, resulting in emotional problems, withdrawal from society, and depression.2 The pathogenesis of acne is multifactorial, and therapy can now be directed at many of these factors. This review summarizes current concepts of the rational treatment of acne vulgaris. Pathophysiology of Acne Acne vulgaris is the result . . .
Article
Despite anecdotal evidence of a possibility of decreased effectiveness of oral contraceptives (OCs) with some antibiotics, it is not known whether antibiotic use in dermatologic practices engenders any increased risk of accidental pregnancy. Our purpose was to examine the effect of commonly prescribed oral antibiotics (tetracyclines, penicillins, cephalosporins) on the failure rate of OCs. The records from three dermatology practices were reviewed, and 356 patients with a history of combined oral antibiotic/OC use were surveyed retrospectively. Of these patients, 263 also provided "control" data (during the times they used OCs alone). An additional 162 patients provided control data only. Five pregnancies occurred in 311 woman-years of combined antibiotic/OC exposure (1.6% per year failure rate) compared with 12 pregnancies in 1245 woman-years of exposure (0.96% per year) for the 425 control patients. This difference was not significant (p = 0.4), and the 95% confidence interval on the difference (-0.81, 2.1) ruled out a substantial difference (> 2.1% per year). There was also no significant difference between OC failure rates for the women who provided data under both conditions, nor between the two control groups. All our data groups had failure rates below the 3% or higher per year, which are typically found in the United States. The difference in failure rates of OCs when taken concurrently with antibiotics commonly used in dermatology versus OC use alone suggests that these antibiotics do not increase the risk of pregnancy. Physicians and patients need to recognize that the expected OC failure rate, regardless of antibiotic use, is at least 1% per year and it is not yet possible to predict in whom OCs may fail.