17-ketosteroids and Acne-Vulgaris

17beta-Hydroxysteroid dehydrogenases (17beta-HSDs) mainly catalyze the reduction of C17-ketosteroids to their corresponding hydroxylated forms as well as the reverse reaction (oxidation). Able to convert inactive or less active steroid hormones into more potent ones and vice versa, certain 17beta-HSDs play a key role, especially in the regulation of estrogen and androgen levels. The therapeutic potential of this enzyme family, especially for the treatment of breast cancer, prostate cancer, acne and osteoporosis, then stimulated the development of inhibitors of 17beta-HSDs and important progress was achieved over the last years.. This review article reports all patent applications related to the inhibitors of 17beta-HSDs, including some articles needed to complement the information presented.. Readers will be informed about the role and function of 17beta-HSDs in the first section and about the history of inhibitor development in the second section. Furthermore, in the third and main section, the readers will learn about the structures of patented inhibitors originating from different companies and academic groups.. The increase in the number of 17beta-HSD inhibitors reported in the last years augurs well for the future. The challenge is now to translate these results into clinical studies to allow determination of the therapeutic usefulness of 17beta-HSD inhibitors.

Topics: 17-Hydroxysteroid Dehydrogenases; 17-Ketosteroids; Acne Vulgaris; Animals; Clinical Trials as Topic; Drug Design; Enzyme Inhibitors; Humans; Neoplasms; Osteoporosis; Patents as Topic

The ongoing development and gradual availability of the new anti-androgens hold exciting clinical implications for the future. The biosynthesis and interchangeability of the sex steroids, the roles of the ovaries and adrenals and the value and interpretation of biochemical assays in clinical practice are briefly discussed. Because the anti-androgens are used primarily for seborrhoea/acne/hirsutism/oligomenorrhoea, the pathophysiological basis of this socially debilitating syndrome is discussed. The classification of the anti-androgens, their indications, side-effects, dosage schemes and results of treatment are reviewed. Finally, a summary of a possible clinical management regimen is presented.

Topics: 17-Ketosteroids; Acne Vulgaris; Adrenal Hyperplasia, Congenital; Androgen Antagonists; Androgens; Androsterone; Contraceptives, Oral, Hormonal; Cyclopentanes; Cyproterone; Dermatitis, Seborrheic; Dihydrotestosterone; Estradiol Congeners; Female; Follicle Stimulating Hormone; Glucocorticoids; Hirsutism; Humans; Hydroxysteroids; Luteinizing Hormone; Male; Medroxyprogesterone; Nandrolone; Prostatic Neoplasms; Receptors, Androgen; Sex Hormone-Binding Globulin; Steroids; Testosterone

Topics: 17-Ketosteroids; Acne Vulgaris; Androgen-Insensitivity Syndrome; Androgens; Female; Glucocorticoids; Hirsutism; Humans; Male; Methods; Polycystic Ovary Syndrome; Protein Binding; Secretory Rate; Skin; Testosterone

Topics: 17-Ketosteroids; Acne Vulgaris; Animals; Cortisone; Dehydroepiandrosterone; Endocrinology; Estrogens; Female; Gonadal Steroid Hormones; Humans; Male; Rats; Sebaceous Glands; Skin; Testosterone; Tetracycline

Treatment of virilization symptoms in 230 patients is reported. 68 patients were treated with Planovin (4 mg megestrol acetate and .05 mg ethinyl estradiol), 77 with SH81041 (100 mg Cyproterone acetate for 10 days and .05 mg ethinyl estradiol for 21 days), and 85 were treated first and Planovin and then with SH81041. Acne, seborrhea, hirsutism, and alopecia improved under treatment with each preparation; results were similar with acne and alopecia, while SH81041 was somewhat more effective than Planovin in treating seborrhea and hirsutism. Therapeutic results obtained during treatment with SH81041 in acne and alopecia are retained during Planovin treatment, but seborrhea and hirsutism become worse again. Successful treatment was independent of the severity of hirsutism and the duration of of treatment. Side effects included breakthrough bleeding and sweating.

Topics: 17-Ketosteroids; Acne Vulgaris; Adolescent; Adult; Alopecia; Androgen Antagonists; Clinical Trials as Topic; Cyproterone; Dermatitis, Seborrheic; Ethinyl Estradiol; Female; Hirsutism; Humans; Megestrol; Virilism

Topics: 17-Ketosteroids; Acne Vulgaris; Adult; Antidepressive Agents, Tricyclic; Chronic Disease; Dibenzocycloheptenes; Female; Gas Chromatography-Mass Spectrometry; Humans; Mass Spectrometry; Middle Aged

22 adult females with therapy-resistant acne vulgaris were treated for 12 months with Diane, a drug containing cyproterone acetate and ethinylestradiol. Treatment was withdrawn in 7 patients because of side-effects of lack of of effect. In the remaining 15 patients, the treatment had extremely promising results, from 70 to 90% improvement of the acne. In a remarkably high number of patients, the androgen production, measured by the urinary excretion of fractional 17-ketosteroids, was elevated. None of these patients had signs of endocrinological diseases, in particular no cases of hirsutism of Stein-Leventhal syndrome were found. The current concept of the course of acne is that the conversion in the skin of testosterone to dehydrotestosterone is increased. The finding of an elevated urinary excretion of androgenic substances in this group of acne patients indicates that the pathogenesis is far more complicated.

Topics: 17-Ketosteroids; Acne Vulgaris; Adult; Contraceptive Agents, Male; Cyproterone; Cyproterone Acetate; Drug Combinations; Ethinyl Estradiol; Female; Humans; Hydrocortisone; Testosterone

Five females with idiopathic hirsutism, ten with adrenogenital syndrome, four with acne vulgaris, and three with Stein-Leventhal syndrome were treated for nine months with large or small doses of cyproterone acetate (100 or 2 mg daily, respectively) in combination with oestrogen. The drug had a good effect on the acne vulgaris and moderated the hirsutism. In the various patient groups the serum testosterone level was decreased to between 58.6% (+/- 28.7% S.E.) and 10.8% (+/- 8.2% S.E.) of the basal value. No essential difference in effectiveness was observed between the large and small doses. Based on study of the side-effects, it is recommended that laboratory liver tests are used for control.

Topics: 17-Ketosteroids; Acne Vulgaris; Adolescent; Adrenal Hyperplasia, Congenital; Adult; Alanine Transaminase; Aspartate Aminotransferases; Cyproterone; Cyproterone Acetate; Female; Hirsutism; Humans; Hydrocortisone; Polycystic Ovary Syndrome; Testosterone

Cyproterone acetate, combined with ethinyl estradiol, was administered to 60 women (mean age: 25 years) suffering from hirsutism, acne and alopecia for 3--39 months. The rate of success was 94% for acne, 85% for hirsutism and 55% for alopecia. These results are comparable to those already reported. No correlation was found between the degree of the disease or plasma levels of testosterone, androstenedione, respectively urinary 17-cetosteroids, and the effectiveness of the treatment. Side effects were rare and identical in frequency and nature to those encountered during treatment with estrogen-containing contraceptives.

Topics: 17-Ketosteroids; Acne Vulgaris; Adult; Alopecia; Androstenedione; Cyproterone; Female; Hirsutism; Humans; Testosterone

28 cases of moderate to severe hirsutism, two cases of acne and one case of axilary hidrosadenitis were tested continuously on average over 6 months by the daily administration of 100 mg cyproterone acetate. This drug was then given together with 1-2 mg oestradiol valerate over a further 6 month period by reversed sequential therapy. The effect of treatment was judged as being moderate only in 7 cases of idiopathic and one case of adrenal hirsutism and good in the remaining cases. However, this regimen caused a marked lowering of the urinary dehydroepiandrosterone sulphate and low polar oestrogen levels and also the plasma testosterone level. At the same time, according to preliminary results, the fraction of sex hormone binding globulin was raised. The plasma hydrocortisone level was depressed by about 20%. The fractions of 17-KS and 17-KGS decreased slightly at first, but then returned to normal. The side effects of continuous treatment were mainly gestagenic and of reversed sequential therapy mainly oestrogenic in nature. The continuation rate was 81% during a treatment period of two years.

Topics: 17-Ketosteroids; Acne Vulgaris; Adult; Cyproterone; Dehydroepiandrosterone; Drug Therapy, Combination; Estradiol; Estrogens; Female; Hirsutism; Humans; Hydrocortisone; Lymphadenitis; Middle Aged; Testosterone; Virilism

Tablets containing 2 mg cyproterone acetate and 0.05 mg ethinyl estradiol in a calendar package of 21 days were used as an oral contraceptive to treat acne. The series comprised 20 patients. The women were 18--43 years of age, and all had acne which had previously been resistant to therapy. The treatment was continued for 6 months. Serum testosterone, 17-OHCS, 17-KS, serum ALAT and gamma-GT were recorded prior to the treatment at 3 and 6 months. Ten patients responded well to the treatment, 5 responded moderately well, 3 experienced no change, and 2 became worse. The serum testosterone level fell during the therapy and the ALAT level rose, though only one pathological ALAT value was recorded.. 20 female patients aged 18-43 had acne which had resisted previous treatment. They were prescribed 21 day cycle oral contraceptives containing 2 mg cyproterone acetate and .05 mg ethinyl estradiol. Treatment was continued for 6 months. Serum testosterone, 17-OCHS, 17-KS, serum ALAT, and gamma-GT were recorded prior to the treatment, at 3 and 6 months. 10 patients responded well to the treatment, 5 moderately well; 3 no change, and 2 became worse. During therapy the serum testosterone level fell and the ALAT level rose. Only one pathological ALAT value was recorded.

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Acne Vulgaris; Adolescent; Adult; Alanine Transaminase; Aspartate Aminotransferases; Cyproterone; Drug Combinations; Drug Evaluation; Ethinyl Estradiol; Female; Humans; Tablets; Testosterone

The effectiveness of therapy with cyproterone acetate and ethinyl estradiol was studied in 103 women. Acne and seborrhea responded best with 91.7 and 93.3% respectively, including complete and partial therapeutic success. For hirsutism complete remission and partial improvement were found in 75.3% of the treated women. Under therapy, body weight did not change in 51.9%, while 24.7% of the patients gained weight and 23.4% lost weight. The cycle length remained normal after therapy in 35.8%. Normalization or improvement was found in 54.7%. In 6.3% no improvement was noted after therapy and in 3.2% cycle irregularity developed in women with previous undisturbed pattern. According to BBT, improvement of the functional capacity of the reproductive system was found in 32.9% of the patients. Only 3% of the women studied demonstrated a deterioration. The 17-ketosteroid excretion was diminished in 35.3% after therapy and remained unchanged in 64.7%. The therapeutic regimen used for the study was well tolerated and good cycle control was obtained.

Topics: 17-Ketosteroids; Acne Vulgaris; Adolescent; Adult; Body Temperature; Body Weight; Cyproterone; Dermatitis, Seborrheic; Ethinyl Estradiol; Female; Hirsutism; Humans; Menstruation; Menstruation Disturbances; Remission, Spontaneous

Fifty-two children, age 5-10, from acne-prone families, were studied for a period of 1 year to examine the interrelationship between sebum, acne, pubertal development, and urinary steroid excretion. In each of the subjects, 30 boys and 22 girls, the composition of forehead skin lipid was determined 4 times yearly by thin-layer chromatography, with measurement of triglycerides, diglycerides, free fatty acids, wax esters, squalene, cholesterol, and cholesterol esters. Twice yearly, examination was made of the presence or absence of acne, pubertal maturation and the 24-hour urinary excretion of testosterone as determined by radioimmunnoassay, and of total 17-ketosteroids, dehydroepiandrosterone, androsterone, and etiocholanolone, as determined by paper chromatography. The relative amount of sebaceous lipids was positively correlated with age of the subjects (wax esters p less than .001, squalene p less than .05), as was the triglyceride-diglyceride component (p less than .05). No significant correlation was seen with the fatty acids. Acne, primarily comedonal, occurred in 27/52 subjects (15 girls, 12 boys) and was associated with higher sebum values. One-half of the children with acne had no signs of pubertal development. A significantly positive correlation was observed between the relative amount of sebaceous lipid and the urinary excretion of 17-ketosteroids, androsterone, and etiocholanolone in both sexes, and of testosterone and dehydroepiandrosterone in boys. The development of acne in children is an early pubertal event, often evident before other signs of pubertal maturation, and it is associated with an increase in sebum and in the urinary excretion of androgenic steroids.

Topics: 17-Ketosteroids; Acne Vulgaris; Child; Child, Preschool; Female; Humans; Lipids; Male; Puberty; Sebum; Skin; Testosterone

Topics: 11-Hydroxycorticosteroids; 17-Ketosteroids; Acne Vulgaris; Adult; Endocrine System Diseases; Female; Humans; Hydrocortisone; Injections, Intravenous; Liver Diseases; Male

Adolescent girls and single women with progressive hirsutism due to polycystic ovaries present a therapeutic dilemma. Clomiphene citrate is useful only to induce ovulation and has no beneficial effect on hirsutism. Surgical wedge resection of these ovaries usually arrests progression of hirsutism and restores ovulatory menses. Such treatment, however, is best reserved until such time as pregnancy would be an equal objective. Treatment of 5 patients by hypothalamic-pituitary-ovarian suppression with 100-mg estradiol pellets implanted subcutaneously every 6 months reduced ovarian size in all 5 patients and halted the progression of hirsutism.

Topics: 17-Ketosteroids; Acne Vulgaris; Adolescent; Adult; Estradiol; Female; Follicle Stimulating Hormone; Hirsutism; Humans; Luteinizing Hormone; Medroxyprogesterone; Menstruation Disturbances; Ovarian Function Tests; Polycystic Ovary Syndrome

Topics: 17-Ketosteroids; Acne Vulgaris; Adrenal Glands; Adult; Blood Cell Count; Cushing Syndrome; Diabetes Complications; Diagnosis, Differential; Ecchymosis; Female; Hirsutism; Humans; Hydrocortisone; Hypertension; Ketosteroids; Male; Obesity

Topics: 17-Ketosteroids; Acne Vulgaris; Adult; Humans; Klinefelter Syndrome; Male; Testosterone

Topics: 17-Ketosteroids; Acne Vulgaris; Adolescent; Adrenocortical Hyperfunction; Adult; Androgens; Child; Dexamethasone; Endocrine System Diseases; Estrogens; Female; Hirsutism; Humans; Menstruation Disturbances; Obesity; Ovarian Diseases; Progesterone

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Acne Vulgaris; Adolescent; Adrenal Glands; Adult; Androgens; Chorionic Gonadotropin; Corpus Luteum; Corpus Luteum Hormones; Dexamethasone; Estrogens; Female; Humans; Progestins

Topics: 17-Ketosteroids; Acne Vulgaris; Adrenal Cortex Hormones; Anti-Bacterial Agents; Betamethasone; Dermatitis; Fludrocortisone; Humans; Hydrocortisone; Intestinal Diseases; Intestine, Small; Ointments; Prednisolone; Psoriasis; Skin Diseases; Tetracycline

Topics: 17-Ketosteroids; Acne Vulgaris; Age Factors; Humans; Infant; Male

Topics: 17-Ketosteroids; Acne Vulgaris; Age Factors; Humans; Infant; Male

Topics: 17-Ketosteroids; Acne Vulgaris; Adenoma; Adrenal Gland Neoplasms; Adrenalectomy; Child, Preschool; Cortisone; Female; Humans; Virilism

Topics: 17-Ketosteroids; Acne Vulgaris; Adolescent; Adrenal Cortex Hormones; Amenorrhea; Clitoris; Female; Hirsutism; Hoarseness; Humans; Ovarian Neoplasms; Sertoli-Leydig Cell Tumor

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Acne Vulgaris; Adolescent; Adult; Atrophy; Back; Child; Female; Humans; Lumbosacral Region; Male; Obesity; Sex Factors; Skin; Skin Diseases

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Acne Vulgaris; Adolescent; Adult; Androgen Antagonists; Androgens; Dimethyl Sulfoxide; Female; Humans; Male; Pharmaceutical Vehicles; Pregnanes; Sebum

Topics: 17-Ketosteroids; Acne Vulgaris; Adolescent; Adult; Dehydroepiandrosterone; Female; Histocytochemistry; Humans; Male; Sex Factors; Skin

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Acne Vulgaris; Adenoma; Adrenal Gland Neoplasms; Adrenal Hyperplasia, Congenital; Carcinoma; Child; Child, Preschool; Dehydroepiandrosterone; Female; Hirsutism; Humans; Infant; Lung Neoplasms; Male; Neoplasm Metastasis; Radiography; Virilism

Topics: 17-Ketosteroids; Acne Vulgaris; Adolescent; Adult; Contraceptives, Oral; Dermatitis, Seborrheic; Estrogens; Female; Humans; Hypertrichosis; Menstruation Disturbances; Mestranol; Ovulation; Progestins; Virilism

Topics: 17-Ketosteroids; Acne Vulgaris; Adolescent; Adult; Chorionic Gonadotropin; Estrogens; Female; Gastric Juice; Gonadotropins, Pituitary; Humans; Liver; Lynestrenol; Male; Pregnanediol

Topics: 17-Ketosteroids; Acne Vulgaris; Adolescent; Chromatography, Paper; Estrogens; Female; Humans; Male; Methods; Vitamin A; Vitamin B Complex

Topics: 17-Ketosteroids; Abscess; Acne Vulgaris; Adolescent; Adrenal Glands; Adult; Female; Humans; Male

Topics: 17-Ketosteroids; Acne Vulgaris; Dehydroepiandrosterone; Female; Glucosephosphate Dehydrogenase; Humans; Male; Sebaceous Glands; Sebum

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Abscess; Acne Vulgaris; Adolescent; Adrenal Glands; Adult; Female; Humans; Male

Topics: 17-Ketosteroids; Acne Vulgaris; Adolescent; Dehydroepiandrosterone; Female; Glucocorticoids; Gonadal Steroid Hormones; Humans; Male; Middle Aged; NADP; Prednisolone

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Acne Vulgaris; Adolescent; Adrenal Hyperplasia, Congenital; Adrenocortical Hyperfunction; Adult; Amenorrhea; Brain; Diagnosis; Female; Hirsutism; Humans; Hypertension; Metabolic Diseases; Mixed Function Oxygenases; Obesity; Urine; Virilism

Topics: 17-Ketosteroids; Acne Vulgaris; Adolescent; Adult; Child; Chromatography, Paper; Female; Hirsutism; Humans; Male; Urine

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Acne Vulgaris; Adrenal Cortex Hormones; Adrenal Gland Neoplasms; Adrenocortical Carcinoma; Adrenocorticotropic Hormone; Androgens; Androsterone; Antineoplastic Agents; Diuretics; Edema; Estrogens; Etiocholanolone; Feminization; Humans; Hydroxylation; Hypertension; Male; Metyrapone; Neoplasms; Pharmacology

Topics: 17-Ketosteroids; Acne Vulgaris; Adolescent; Biomedical Research; Body Fluids; Humans; Male; Metabolism; Sebum; Sex; Urine

Topics: 17-Ketosteroids; Acne Vulgaris; Adrenocortical Hyperfunction; Alopecia; Chromatography; Female; Hirsutism; Humans; Hypertrichosis; Staphylococcal Infections; Urine

Topics: 17-Ketosteroids; Acne Vulgaris; Body Fluids; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Urine

Topics: 17-Ketosteroids; Acne Vulgaris; Adrenocorticotropic Hormone; Female; Humans; Hydrocortisone; Hypertrichosis; Infertility; Infertility, Female; Menstruation Disturbances; Metrorrhagia; Ovary; Ovulation; Urine

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Acne Vulgaris; Adrenal Cortex Hormones; Humans

Topics: 17-Ketosteroids; Acne Vulgaris; Biological Transport; Body Fluids; Steroids; Urine; Vitamin A

Topics: 17-Ketosteroids; Acne Vulgaris; Humans; Pregnanediol; Steroids; Urine

Topics: 17-Ketosteroids; Acne Vulgaris; Body Fluids; Humans; Male; Steroids; Urinary Tract

Topics: 17-Ketosteroids; Acne Vulgaris; Diethylstilbestrol; Humans; Male; Urinary Tract

Topics: 17-Ketosteroids; Acne Vulgaris; Androgens; Humans