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Context: Hypothalamus-pituitary-gonadal (HPG)-axis disturbances are a common phenomenon in patients with classic congenital adrenal hyperplasia (CAH). 11-oxygenated androgens have been suggested to play a role in this context., Design: Cross-sectional single center study including 89 patients (N = 42 men, N = 55 women) with classic CAH., Main Outcome Measures: Differences in steroid markers in men with hypogonadism and women with secondary amenorrhea with a special focus on 11-ketotestosterone (11KT) and 11β-hydroxyandrostenedione (11OHA4)., Results: Hypogonadotropic hypogonadism was present in 23 % of men and 61 % of those women currently not on contraceptives suffered from irregular menstrual cycles or amenorrhea. Testicular adrenal rest tumor (TART) was documented in 28 % of men. 11KT (3.5x) and 11OHA4 (5.7x) among other adrenal steroids were significantly elevated in men with hypogonadism and in women with amenorrhea in comparison to those with a regular cycle (11KT: 5.2x; 11OHA4: 3.7x). 11-oxygenated androgens were not higher in men with TART than in those without. There was a negative association of 11KT and 11OHA4 with FSH but not with LH in men. As expected, all steroids were strongly correlated with each other and cases of disproportionally elevated 11-oxygenated androgens that could explain for HPG-disturbances or TART in otherwise controlled patients were rare and also found in eugonadal individuals., Conclusions: In CAH, 11-oxygenated androgens are elevated in women with menstrual disturbances and in men with hypogonadotropic hypogonadism. Due to the close correlation of 11-oxygenated androgens with other adrenal steroids it remains to be shown if their measurement is superior to conventional markers of androgen control., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Context: Epidemiologic studies of polycystic ovary syndrome (PCOS) are limited, especially in populations where diagnostic resources are less available. In these settings, an accurate, low-cost screening tool would be invaluable., Objective: To test the use of a simple questionnaire to identify women at increased risk for PCOS and androgen excess (AE) disorders., Study Design: Prospective cohort study from 2006-2010., Setting: Community-based., Participants: Women aged 14 to 45 years., Intervention: A screening telephone questionnaire consisting of 3 questions was tested, where participants were asked to self-assess the presence/absence of male-like hair and menstrual irregularity. Participants were then invited to undergo a direct examination, including completing a medical history and undergoing a modified Ferriman-Gallwey (mFG) hirsutism score, ovarian ultrasound, and measurement of circulating total and free testosterone, DHEAS, TSH, prolactin and 17-hydroxyprogesterone levels., Main Outcome Measure: Accuracy of questionnaire in predicting PCOS, AE, and irregular menses., Results: Participants with self-assessed irregular menses and/or excess hair were labeled "Possible Androgen Excess (Poss-AE)" and those self-assessed with regular menses and no excess hair were labeled "Probable Non-Androgen Excess (Non-AE)." The study was completed in 206/298 (69%) of the Poss-AE and in 139/192 (73%) of the Non-AE. Of Poss-AE and Non-AE subjects, 82.5% and 15.8%, respextively, presented with PCOS. The calculated sensitivity, specificity, positive predictive value, and negative predictive value of the 3-question telephone survey to predict PCOS was 89%, 78%, 85%, and 83%, respectively., Conclusions: A simple telephone questionnaire, based on self-assessment of body hair and menstrual status, can be used with a high predictive value to identify women at risk for AE disorders, including PCOS, and to detect healthy controls. This approach could be an important tool for needed epidemiologic studies., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Androgen is a steroid hormone associated with high blood pressure (BP). The effect of androgen on BP in females is unknown., Methods: Androgen, vascular endothelial growth factor (VEGF), interleukin (IL)-6 and matrix metalloproteinase (MMP)-9 were evaluated in females with menstruation disorders (n = 135, 28 ± 5 years old) and normal BP, pre-hypertension, stage 1 hypertension, and stage 2 hypertension., Results: Normal-BP (n = 57), pre-hypertension (n = 44), stage-1-hypertension (n = 21), and stage-2-hypertension (n = 13) females had similar androgen (3.3 ± 1.5, 2.7 ± 1.2, 3.1 ± 1.4, and 3.5 ± 1.3 ng/ml, p > 0.05) and IL-6 levels (1.7 ± 2.2, 1.9 ± 2.6, 1.3 ± 1.2 and 2.4 ± 3.3 pg/ml, p > 0.05). However, normal BP females had lower MMP-9 (609 ± 307 versus 891 ± 385 ng/ml, p < 0.05) than stage-1-hypertension females. In addition, normal BP females had lower VEGF (166 ± 103 versus 255 ± 139, 272 ± 128 and 301 ± 216 pg/ml, p < 0.05) than the other three groups. In normal-androgen females, VEGF levels were similar among the four groups. However, in high-androgen females, normal BP groups had lower VEGF levels than pre-hypertension, stage-1, and stage-2 hypertension groups (166 ± 94 versus 294 ± 153, 281 ± 160 and 357 ± 253 p < 0.05)., Conclusions: Androgen can modulate growth factors and extracellular matrix proteins, which may contribute to the pathophysiology of hypertension in young females.

Reproductive disorders and psychological distress are common co-morbidities of obesity in young women. Psychological and reproductive disturbances may also be associated with increased food cravings but the relationships between these factors have not been explored. This study aimed to explore the pattern of food cravings and to determine the relationship between psychological distress, reproductive health and food cravings in overweight and obese young women using baseline data in a weight loss trial. A total of 198 young women were included in this analysis (BMI 33.3+/-0.3 kg/m(2), age 28+/-0.3 years). The most frequently craved food item was chocolate (3.9+/-0.08 i.e., sometimes-often). The most frequently craved food categories were fast foods (2.6+/-0.07) and sweets (2.5+/-0.05). Psychological distress was significantly correlated with food cravings (R(2)=0.18, P<0.05). High fat (r=0.2), sweets (r=0.17) and overall cravings (r=0.20) were significantly correlated with energy intake (P<0.05). Psychological distress did not correlate with energy intake (P>0.05). Participants with menstrual disturbances had greater fast food cravings independent of age, BMI and PCOS status (P<0.05). Participants with hyperandrogenemia had greater high fat food cravings independent of age, BMI and PCOS status (P<0.01). Energy intake did not differ with menstrual disturbances or hyperandrogenemia (P>0.05). These results suggest that psychological distress, hyperandrogenemia and menstrual disturbances are associated with greater food cravings. Further investigations are required to elucidate the relationship between hyperandrogenemia and food cravings in young women.

The objective of this cross-sectional study was to determine the relationship between hyperandrogenemia and blood pressure in women with menstrual irregularities seen at an endocrinology clinic. Women with serum testosterone levels (T) > or = 30 ng/dL were more likely to have general obesity (odds ratio [OR] = 6.8, 95% confidence intervals [CI] = 2.2-27.2) and central obesity (OR = 14.5, 95% CI = 6.1-38.7) than euandrogenemic women. Hyperandrogenemic women (HA) had an OR of 2.4 (95% CI = 1.0-6.2) for elevated SBP and an OR of 2.7 (95% CI = 0.8-8.8) for elevated DBP, independent of age and ovulatory status. Obese HA had an OR of 4.7 (95% CI = 2.3-10.4) for elevated SBP and an OR of 2.9 (95% CI = 1.9-9.9) for elevated DBP. In conclusion, T is associated with an increased risk for obesity and central adiposity. T predicts BP elevation independent of age and ovulatory status. There was a synergistic relationship between obesity and androgens in their affect on BP.

ACTH, prolactin, hydrocortisone, 17 OH-progesterone, androstenedione, dehydroepiandrosterone C, and testosterone were measured in the blood of 36 androgenic women and 8 healthy ones before and after adrenal stimulation. The findings evidence that various mechanisms are responsible for the development of androgynism of an adrenal origin. In patients with congenital virilizing adrenocortical hyperplasia and 21 hydroxylase deficiency excessive androgen production results mainly from activation of delta-4 route of androgen synthesis; in patients with adrenal androgynism and insufficiency of enzymic systems of steroidogenesis the androgen production is explained by functional hyperactivity of the bundle and retinal zones of the adrenal cortex and hyperreactivity to stimulating factors. Hyperproduction of androgens is related to ovarian hyperproduction of not only androstenedione and testosterone, but, in some patients, of dehydroepiandrosterone C as well. Elevated basal blood level of this enzyme cannot be regarded as a sufficiently reliable criterion in the differential diagnosis of the adrenal or ovarian origin of androgynism.

In order to study the changes in androgen levels in patients with polycystic ovary syndrome (PCOS), serum androgen levels (testosterone [T], free-testosterone [free-T] and sex-hormone-binding globulin [SHBG]) were measured and related to the incidence of menstrual abnormalities, obesity and hirsutism. Tests were made in 61 cases of PCOS identified by transvaginal ultrasound and in normal controls. The following results were obtained: 1) The PCOS group with menstrual irregularities had significantly higher levels of T and free-T than the control group, but SHBG levels were not significantly altered. 2) The obese group had significantly higher free-T levels than the non-obese group, and SHBG was significantly lowered. 3) There were significant correlations between the levels of obesity and free-T and SHBG. 4) T and free-T were moderately high in the hirsutism group and SHBG was moderately low, but not significantly so. These findings indicate that, in PCOS patients, serum androgen levels, especially free-T and SHBG, are closely related to menstrual irregularities and the level of obesity.

Adrenocortical and ovarian function in women with hyperprolactinemia and hyperandrogenism was evaluated using the functional ACTH1-24-test (with syncorpin--25 U/ml), a radioimmunoassay was used to estimate the levels of II-OCS, androgens, progestins, estrogens and prolactin in the blood serum of 29 women with primary prolactinemic hypogonadism (HG), in 15--with hyperandrogenic ovarian dysfunction, in 27--with the hypothalamic syndrome of neuro-endocrine type, and in 13 healthy women. Marked interference of a clinical picture was found in patients with disturbed menstrual and reproductive function with relation to the presence of galactorrhea and hirsutism. All the examinees retained glucocorticoid function. Patients with hyperprolactinemia demonstrated an increase in the basal concentration of the ovarian androgen androstenedione in the absence of its response to ACTH. The level of 17-oxyprogesterone in them was decreased. A paradoxical response of prolactin to syncorpin was observed in patients with microprolactinemia, the syndrome of the "empty" Turkish saddle and functional type of HG.

Ninety-seven adolescents (0.5-6.0 years in gynaecological age) suffering from various kinds of menstrual irregularities were studied and compared with 20 adults by performing ovarian ultrasonography and plasma hormonal determinations. High percentages of multifollicularity (57.7%) and enlarged ovaries (46.3%) were found in the entire group of adolescents. Adolescents with multifollicular ovaries (more than 4 cystic areas) showed higher percentages of luteinizing hormone (LH: 32%), testosterone (T: 34%), and androstenedione (A: 43%) levels exceeding the upper normal adult range than subjects with homogeneous (less than 4 cystic areas) ovaries (LH: 12%, T: 10%, A: 19%, respectively). Ovulation can further discriminate the adolescents: in fact, adolescents with homogeneous ovaries and ovulatory cycles have a hormonal pattern almost identical to that of adults. On the contrary, subjects with multifollicular ovaries and anovulatory cycles show low values of follicle-stimulating hormone (FSH) and high values of LH, T and A, significantly different from those in ovulatory subjects with homogeneous ovaries (P less than 0.005) and from those in adults (P less than 0.005).

Seventeen patients with irregular menstrual periods and androgenic symptoms such as excessive hair growth, acne, and oily skin were treated with spironolactone. The basal levels of serum testosterone (T), dihydrotestosterone (DHT), estradiol (E2), and luteinizing hormone (LH) were significantly higher in the patients than in the controls. After a 4-week treatment with spironolactone, serum T and DHT showed significant decreases. Before treatment, the serum sex hormone binding globulin (SHBG) levels were significantly lower in the patients than in the controls. After initiation of the spironolactone treatment, the SHBG levels tended to increase but not significantly. Spironolactone treatment resulted in the improvement or disappearance of acne in 4 of 5 patients who suffered from this ailment. Improvement of hirsutism was obtained in 2 of 10 patients. Although 4 oligomenorrheic patients and 6 amenorrheic patients showed anovulatory bleeding but did not ovulate, 2 patients in the amenorrheic group ovulated. Two patients complained of tiredness and weakness, and 2 others of polyuria and polydipsia. Both groups showed only temporary symptoms, so treatment was not interrupted. Spironolactone has beneficial effects on ovarian function and few side effects, so it may prove to be an effective anti-androgen, especially for hyperandrogenic anovulatory patients.

Androgenetic alopecia (a.A.) occurs quite frequently. Up to 79% of women suffer at least temporarily from varying degrees of intermittent diffuse hair loss in the centro-parietal and/or fronto-temporal regions. A.A. is caused by an androgen excess acting on the hair follicle for prolonged periods of time in the presence of a genetic predisposition. However, often hyperandrogenemia cannot be demonstrated in such patients. 125 women with clinically typical a.A. were investigated prospectively under standardized conditions. Patient age ranged from 18 to 68 years (mean +/- SD: 34 +/- 11.6). Atypical uterine bleeding such as menorrhagia, hypermenorrhea and polymenorrhea were found in 69 women. The hair loss varied between 50 and 400 hairs per day (124 +/- 125). Additional signs of hyperandrogenism, i.e. seborrhea (n = 83), acne (n = 52) and hirsutism (n = 28), were often observed. Basal levels of total and free testosterone (T and FT), dihydro-T (DHT) DHEA-sulfate (DS), delta 4-androstendione (A), 17 alpha-hydroxy-progesterone (17P), cortisol (F), progesterone (P), 17 beta-estradiol (E2), sex hormone binding globuline (SHBG), prolactin (PRL), thyreoidea-stimulating hormone (TSH), ferritin (Fe), vitamin B12 (B12) and folat (Fo) were determined by RIA. FT was also measured by equilibrium dialyses. Different methods of determining bound and unbound T were used; their diagnostic value is discussed in detail. In addition, a combined ACTH/TRH-stimulation test was performed in all patients. Pathologic changes of one parameter were detectable in 26.4% of patients, while 67.2% revealed deviations of two or more indices. Excluding clinically relevant borderline values, only 6.4% of patients were without any abnormalities. The incidence rate of pathologic parameters was as follows: FT in % = 52%, Fe = 42%, PRL = 34%, E2 = 34%, FT in pg = 29%, DHT = 28%, SHBG = 26%, TSH = 20.8%, DS = 19%, T = 14%, 17P = 11%, Fo = 7%, A = 6%, F = 6%, B12 = 5%. Group and individual case analyses revealed significant correlations between (1) the levels of the various androgens, PRL and TSH and (2) the E2, SHBG and FT values; these, in turn, were correlated to (3) the occurrence of certain bleeding anomalies (amount, duration, interval) and corresponding ferritin deficiency. Therapy was directed at normalizing the disturbed estrogen-androgen-balance. Using low-dose antiandrogens, estrogens, prolactin suppressants, corticoids, iron-II-preparations as well as estrogen-containing hair lotions hair loss was arrested in 74 of 104 treated women, while regrowth of hair was accomplished in 16 patients. 14 women did not respond to therapy.

The plasma concentrations of total testosterone, free testosterone index, androstenedione, 17 beta-estradiol, luteinizing hormone, follicle-stimulating hormone, prolactin, and urinary 17-ketosteroid and 17-ketogenic steroid excretion were measured in 48 nonhirsute and 119 hirsute patients. Hormone data were compared within and between groups according to whether the menstrual cycles were eumenorrheic, amenorrheic, or oligomenorrheic. Eleven hirsute women treated with prednisone were followed for 6 months. It was concluded that: (1) androstenedione, testosterone, free testosterone index, and adrenal androgens alone or in combination play a role in the pathogenesis of the hirsutism observed in eumenorrheic women and in the amenorrhea and oligomenorrhea of both hirsute and nonhirsute women; (2) body weight correlated with adrenal adrogens (17-ketosteroids) in nonhirsute women and with androstenedione in hirsute women; (3) prednisone significantly suppressed androstenedione and 17-ketosteroids (p less than 0.05), with a decline of testosterone to 65% and luteinizing hormone to 51% of pretreatment values, with favorable clinical effects on the hirsutism, menstrual dysfunction, and infertility; (4) concentrations of 17 beta-estradiol were lower in amenorrheic than in eumenorrheic and oligomenorrheic women of both groups.

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.

The androgen status was determined in 105 women with hirsutism. Raised values of at least one androgenic hormone was found in 58 women, most frequently free testosterone, dehydroepiandrosterone sulphate and delta-4-androstendion. No significant correlation was found between the androgen level and the degree of hirsutism or the frequency of disturbances of menstruation apart from amenorrhoea. Fifty-three women were examined at least six months after the electroepilation therapy. Significant decrease in the degree of hirsutism and the frequency of self-treatment were found together with great satisfaction with the result of treatment.

It is important to diagnose hyperandrogenism in women. By disturbing ovulation, it is actually one of the most frequent causes of infertility. In this particular case, its diagnosis has specific implications: sometimes specific treatment is indicated, or the risk of fetal virilization should be prevented. There is always the possibility of a diagnosis of polycystic ovary, prompting precautionary measures to be taken that are likely to limit the risks linked to the multifollicular development that is so frequent with this disorder. In addition, hyperandrogenism exposes the patient to various gynecological and general complications: cancer of the endometrium, progressive increase in menstrual disturbances and infertility, obesity, metabolic disturbances and probably increase in cardiovascular risks. Certain types of hyperandrogenism give rise to diseases that expose the patient to specific risks: virilizing tumors, Cushing's syndrome, neonatal risks linked to congenital hyperplasia of the adrenal glands. Hyperandrogenism should be borne in mind not only when the clinical picture is that of virilization, but also when there is any disturbance in eugonadal ovulation, whether or not this is manifested as menstrual disturbances or as infertility, and especially whether or not it is accompanied by hirsutism.