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Journal Article 2015; 36(8): 767-770 PubMed PMID: 26921577 Citation  Keywords:  Androgens:pharmacology, Animals, Female, Gonadotropin-Releasing Hormone:drug effects, Hypothalamus:drug effects, Kisspeptins:drug effects, Neuropeptides:drug effects, RNA, Messenger:drug effects, Rats, Rats, Sprague-Dawley, Receptors, G-Protein-Coupled:dr.   

OBJECTIVE: The neonatal and/or prepubertal androgen milieu affects sexual maturation. In rodents, neonatal chronic testosterone treatment, which is used as a model of polycystic ovary syndrome (PCOS), results in the onset of vaginal opening occurring earlier in the pubertal period.

DESIGN: In the present study, the changes in hypothalamic Kiss1 (a gonadotropin-releasing hormone (GnRH)-stimulating factor) and RF-amide related peptide (RFRP; a GnRH inhibitory factor) mRNA expression induced by testosterone treatment were examined in order to clarify whether these factors are involved in the testosterone-induced acceleration of sexual maturation.

RESULTS: The onset of vaginal opening occurred earlier and uterine weight was increased in female rats subjected to chronic (from postnatal day 23 to day 31) testosterone treatment. Contrary to our expectations, the rats' hypothalamic Kiss1 and Kiss1 receptor mRNA levels were not changed, and their serum luteinizing hormone (LH) levels were decreased. Although hypothalamic RFRP mRNA expression was decreased in the testosterone-treated rats, this change was not reflected in their serum LH levels.

CONCLUSIONS: These results indicate that the advancement of sexual maturation observed in chronic testosterone-treated rats might be caused by a peripheral, rather than a central, mechanism....

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Clinical Study 2015; 36(5): 421-429 PubMed PMID: 26707041 Citation  Keywords:  Adolescent, Adult, Aged, Androgens:therapeutic use, Dehydroepiandrosterone:therapeutic use, Estradiol:therapeutic use, Estriol:therapeutic use, Estrogens:therapeutic use, Estrone:therapeutic use, Female, Hormone Replacement Therapy:methods, Humans, Male, .   

OBJECTIVE: In 2002 we suggested a new hypothesis of migraine. This hypothesis implies that migraine is a consequence of a loss of neurohormonal and metabolic integrity. The goal of this clinical analysis is to present the evaluation of the effect of a multimodal treatment program in migraine management.

MATERIAL AND METHODS: We evaluated 30 patients ages 16-66 with migraine who were treated with a multimodal treatment program. All patients received a complex program which included: hormonorestorative therapy (HT) with bio-identical hormones; correction of balance between sympathetic and parasympathetic systems and simultaneously calcium/magnesium balance; "resetting" the pineal gland; improvement of intestinal absorption through restoration of normal intestinal flora, and a cleanse from parasitic infestation (if necessary). Serum levels of total cholesterol (TC), pregnenolone, dehydroepiandrosterone sulfate (DHEAS), progesterone, total estrogen, and total testosterone were determined,

RESULTS: All patients responded to this regimen. We do not have patients who still have migraine after they started to use this program. Laboratory finding prior to HT showed the significant deficiency in production of all basic steroid hormones (progesterone and pregnenolone production declined the most). Concurrent symptoms such as fibromyalgia, insomnia, depression, gastrointestinal disorders, and fatigue had disappeared. Total cholesterol completely normalized in 22 (91.7%) patients. No adverse effects or complications related to this program were registered.

CONCLUSIONS: Our findings support the hypothesis that migraine is a consequence of a loss of neurohormonal and metabolic integrity, and that migraine can be managed by a multimodal approach....

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Comparative Study 2012; 33(8): 787-791 PubMed PMID: 23391972 Citation  Keywords:  17-alpha-Hydroxyprogesterone:blood, Adolescent, Adrenal Hyperplasia, Congenital:drug therapy, Androgens:blood, Androstenedione:blood, Anti-Inflammatory Agents:therapeutic use, Child, Child, Preschool, Dehydroepiandrosterone:blood, Female, Fingers:anatomy .   

OBJECTIVES: Excessive hyperandrogenism, though proper hydrocortisone supplementation is a frequent clinical problem in girls with congenital adrenal hyperplasia (CAH). This may result from autonomic regulation of androgen production established in prenatal life. It has been suggested that the length of the second finger relative to the length of the fourth finger (2D;4D ratio) is negatively related to prenatal testosterone concentration.

DESIGN AND SETTING: The retrospective study aimed to establish the relationship between the level of androgenization in utero determined using 2D:4D ratio and serum androgen concentrations in treated girls with CAH (21-OH deficiency) has been performed on 19 girls with CAH (21-OH deficiency) at the age of 3.7-19 years (mean 13.8 ± 4.07 years). All subjects were adequately treated with hydrocortisone (10-19 mg/m2; mean 13.81 ± 4.07 mg/m2). Anthropometric measurements of digits length were performed in all girls on X-rays obtained for bone age estimation. Apart from it, serum androgens concentrations (testosterone, androstenedione, s-DHEA) and 17-OH-progesterone (17-OHP) were assayed.

RESULTS: Mean androgens serum concentrations in examined group were: testosterone 150.21 ± 155.44 ng/ml; androstenedione 4.15 ± 5.32 ng/ml, s-DHEA 70.39 ± 85.52 µg/dl. Mean 2D:4D ratio was 0.96 ± 0.04. Analysis of correlation showed positive linear correlations between testosterone, s-DHEA and 2D:4D ratio (r=0.53, p=0.023 and r=0.53; p=0.019, respectively).

CONCLUSIONS: 2D:4D ratio parameter may be a simple test in indentification of female CAH patients prone to excessive androgen secretion despite proper treatment. The autonomization of adrenal androgens production in foetal life may cause its elevated levels in female patients with CAH although treated adequately....

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Case Reports 2012; 33(3): 257-259 PubMed PMID: 22635079 Citation  Keywords:  Androgens:metabolism, Female, Humans, Immunohistochemistry, Middle Aged, Ovarian Neoplasms:complications, Ovary:pathology, Sertoli-Leydig Cell Tumor:complications, Testosterone:metabolism, Virilism:etiology,.   

: Sertoli-Leydig cell tumor is a rare and usually unilateral tumor of the ovary occurring in women's reproductive age. Only about 10% of these patients are over 50 years of age. One third of these patients are suffering from signs of virilisation. This work summarizes the morphological and immunohistochemical characteristics of this tumor in a 56-year old woman with clinical signs of virilisation....

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Journal Article 2011; 32(6): 847-856 PubMed PMID: 22286802 Citation  Keywords:  Adult, Amenorrhea:blood, Androgens:blood, Blood Glucose:metabolism, Female, Follicle Stimulating Hormone:blood, Gonadotropin-Releasing Hormone:administration & dosage, Humans, Insulin:blood, Luteinizing Hormone:blood, Oligomenorrhea:blood, Polycystic Ovar.   

OBJECTIVE: As increased frequency of gonadotrophin-releasing hormone (GnRH) pulses is characteristic for polycystic ovary syndrome (PCOS), we assessed gonadotrophin response to GnRH in women with PCOS with normal and raised androgens and in regularly menstruating controls.

DESIGN, PATIENTS AND METHODS: The study involved 155 subjects: PCOS, n=121, age (mean±SD) 24.8±5.4 yrs, BMI 24.5±6.0 kg/m2, all with oligo-/amenorrhoea and PCO morphology, and 34 controls. Gonadotrophins were measured in early follicular phase after GnRH stimulation (0, 30 and 60 minutes).

RESULTS: Fifty four (41.9%) women with PCOS had androgens (testosterone, androstendione, dihydroepiandrosterone sulphate) within the reference range, and would fulfil the "Rotterdam", but not the Androgen Excess Society PCOS criteria. Baseline and stimulated LH concentrations were higher in PCOS (9.09±5.56 vs 4.83±1.71 IU/l, 35.48±31.4 vs 16.30±6.68 IU/l, 33.86±31.8 vs 13.45±5.2 IU/l, at 0, 30 and 60 min post GnRH, respectively, p<0.0001). An LH/FSH ratio in PCOS increased further after GnRH stimulation. ROC analysis revealed that LH30min/FSH30min >2.11 or LH60min/FSH60min >1.72 had 78.3% and 87.5% sensitivity and 81.7% and 81.3% specificity for diagnosis of PCOS. Both baseline and GnRH-stimulated LH and FSH concentrations were similar in women with PCOS and raised androgens and with androgens within the reference range (p=0.71 and p=0.20 for LH and FSH, respectively).

CONCLUSIONS: Regardless of their androgen status, women with PCO morphology and oligo-/amenorrhoea have higher baseline and GnRH-stimulated LH concentrations and higher GnRH-stimulated LH/FSH ratio than controls, suggestive of similar underlying mechanism accounting for menstrual irregularities. These observations support validity of PCOS diagnostic criteria based on the Rotterdam consensus....

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Journal Article 2009; 30(4): 515-524 PubMed PMID: 20010498 Citation  Keywords:  Androgens:pharmacology, Animals, Catalase:metabolism, Cell Division:drug effects, Cell Line, Transformed, Cell Survival:drug effects, Down-Regulation:drug effects, Drug Interactions, Glioma, Glucose:pharmacology, Mice, Microtubules:drug effects, Neuroblas.   

OBJECTIVES: Diabetic complications can often affect the central nervous system since the chronic exposure to hyperglycemia can result in the production of high concentration of reactive oxygen species with subsequent damage of several cell structures such as the cytoskeleton. In order to antagonize the oxidative status many substances have been tested as antioxidants. In the present work attention has been focused on the possible nitrosative effect of hyperglycemia on microtubular network of neuroblastoma and glioma mortalized cell lines, testing the possible neuroprotective effect of testosterone.

METHODS: Neuroblastoma (C1300) and glioma (C6) cell lines were cultured in the presence of 300 mM (C1300) or 310 mM (C6) D-glucose, with or without 50 nM testosterone. After 72 hrs, morphology, growth rate, cell viability and catalase activity were evaluated. In addition, with the aim to detect any changes in the amount of tubulin isoforms, Western blot analysis was performed.

RESULTS: In D-glucose-exposed cells, it was found a down-regulation of tubulin isoforms and an increase in 3-nitro-L-tyrosine and subsequent modifications in cell morphology, growth rate, viability and catalase activity. All these changes were more severe in neuroblastoma than in glioma cell line. When testosterone was added to the medium, all the parameters were very similar to controls. This neuroprotective action was well-detectable in C1300 cells, whereas testosterone was not able to recover significantly in C6 cells.

CONCLUSION: Our results displayed: i) a selective action of high glucose on microtubules; ii) a different sensitivity to oxidative stress in neuronal and glial cells; iii) a different neuroprotective action of testosterone on neuronal and glial cells....

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Historical Article 2008; 29(4): 589-597 PubMed PMID: 18766169 Citation  Keywords:  Androgens, China, Chronobiology Phenomena, Data Interpretation, Statistical, Egypt, History, Ancient, Humans, Male, Models, Theoretical, Periodicity, Social Class,.   

UNLABELLED: DISCOVERY: A periodicity of 500 years has been discovered in the political history of ancient Egypt and documented by means of inferential statistics. Periods of chaos and waning of central power (some of them called "intermediate periods") recurred every 500 years.

DATA & METHODS: Input for the computation is the mean duration of ruling dynasties calculated per each half century. Fisher's periodogram analysis and Halberg's cosinor regression have been used. A highly significant (p < 0.00002) periodicity of approximately 500 years has been found. Data are taken from two different historians and results for low and middle chronology are being compared. FURTHER RESULTS: Lability of dynastic power in ancient Egypt as well as China between 3000 and 500 B. C. culminated each 500 years synchronously. No local events, confined to Egypt or China alone, can serve as an explanation. The rhythm of "dark ages" seems to continue beyond Egyptian and ancient Chinese history into the modern era and seems to be world-wide.

HISTORICAL BACKGROUND: It is a surprising fact, that this periodicity has been known already to the priests of Babylon, who ascribed this to the maleficient influence of god Nergal. The same periodicity has been described by the Chinese philosopher Mencius in the 3rd century B.C. and attributed to the will of tian (heaven). Egyptians elevated their war god Seth every 500 years and European kings assumed masculine nicknames.

CONCLUSION: This recurring cultural pattern of aggressiveness and strife resembles overall traits of male psyche or mid-life crisis. We suggest to look for an unknown cosmophysical factor impacting the neuroendocrine system of man by raising the levels of androgens periodically. EXPLANATION HYPOTHESES: Sun impacts global weather on Earth, but there is no known significant periodicity of 500 years in solar activity. The Wheeler weather cycle almost fits the cycle of Egyptian political history. But his cold-dry periods seem to lag behind the periods of social destabilization and hence can not cause them. An alternative view (based on idealistic rather than materialistic presuppositions) is, that periodic long-term shifts of archetypes take place within the collective unconscious of mankind independently of external environment....

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Comparative Study 2006; 27(6): 763-767 PubMed PMID: 17187005 Citation  Keywords:  Adult, Androgen Antagonists:therapeutic use, Androgens:blood, Androstenedione:blood, Cyproterone Acetate:therapeutic use, Dehydroepiandrosterone:blood, Drug Combinations, Ethinyl Estradiol:therapeutic use, Female, Ghrelin, Humans, Peptide Hormones:blood, .   

OBJECTIVE: Ghrelin is a natural ligand of the growth hormone secretagogue receptor and has been shown to be a potent stimulant of GH secretion. It has also orexigenic effects and regulates energy homeostasis. Recent studies claim that ghrelin influences the androgen level and probably takes part in PCOS pathomechanism. The aim of the study was an assessment of ghrelin level in plasma in women with PCOS before and after the treatment and ghrelin's influence on androgen level change.

MATERIAL AND METHODS: The study included 25 women with the diagnosed PCOS (mean age 25.3+/-4.05 yr). The tests were done twice: before the treatment and after 6-month therapy with Diane 35 (cyproterone acetate 2 mg with ethinylestradiol 35 mug). Following hormones were measured: ghrelin, free testosterone, androstendione, dehydroepiandrosterone sulfate, 17-OH-progesterone and estradiol.

RESULTS: The received results in both groups were compared with the control group (11 healthy women, mean age 26.0+/-2.6 yr). No statistically significant differences in ghrelin levels before (187.8+/-8.1 fmol/ml) and after the therapy (185.6+/-9.5 fmol/ml) were found. Similar results were received when two groups of women compared with the control (186.5+/-8.7 fmol/ml). No correlations between ghrelin and androgen levels were confirmed.

CONCLUSIONS: Final conclusion is that there is no direct impact of ghrelin level on PCOS pathogenesis, however, its role in development of obesity, hyperinsulinemia and insulin resistance co-occurring with metabolic disorders syndrome cannot be excluded....

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