Androstanediol Glucuronide Levels Research Articles

Orale Kontrazeptiva und Androgenisierungserscheinungen

Androgenisierungserscheinungen der Haut können aufgrund einer Hyperandrogenämie, einer vermehrten lokalen Androgenbildung in der Haut oder wegen einer „Hypersensitivität” der Haut gegenüber Androgenen entstehen. Wichtigster pathogenetischer Faktor ist neben einer Erhöhung der Serumkonzentration des gesamten und freien Testosterons eine verstärkte lokale Aktivität der 5α-Reduktase, zu deren Diagnose das Serum-Androstandiolglucuronid jedoch nicht geeignet ist. Alle östrogendominanten Ovulationshemmer bewirken bei 60 - 80 % der Frauen mit Akne und Seborrhö eine Besserung, wobei etwa die Hälfte des Therapieerfolgs auf einen Plazeboeffekt zurückgeführt werden kann. Vermutlich führt die Teilnahme an einer Studie zu einer sorgfältigeren Hautpflege und Vermeidung aknefördernder Faktoren. Die günstige Wirkung der oralen Kontrazeptiva beruht auf einer Senkung der ovariellen und adrenalen Produktion der Androgene und Androgenpräkursoren, einer Erhöhung des SHBG sowie auf einem lokalen Effekt des Ethinylestradiols und der Gestagene, wobei unterschiedliche Mechanismen zum Tragen kommen können. Bei einer androgenetischen Alopezie läßt sich mit Ovulationshemmern, die ein antiandrogen wirksames Gestagen enthalten, bei längerer Behandlung in vielen Fällen eine Besserung erreichen. Bei Frauen mit Hirsutismus sind orale Kontrazeptiva weniger wirksam, doch wird in schweren Fällen nicht selten unter einer längeren Therapie mit einer Kombination von Ethinylestradiol und hohen Dosen von Cyproteronacetat ein günstiger Effekt beobachtet. Präparate, die ein Gestagen mit androgenen Eigenschaften in zu hoher Dosierung enthalten, sind nicht nur weniger wirksam, sondern können sogar bei prädisponierten Frauen Androgenisierungserscheinungen verursachen. Gelegentlich wird aber auch zu Beginn einer Behandlung mit oralen Kontrazeptiva ein leichter diffuser Haarausfall oder eine vorübergehende Verstärkung einer bestehenden Akne beobachtet. Wenn es nach dem Absetzen eines Ovulationshemmers zu einer Akne oder einem Haarausfall kommt, so verschwinden die Symptome meist nach einiger Zeit.

Isolated Absence of Adrenarche in A Postpubertal Female

Background The development of pubic and axillary hair (adrenarche) is part of the process of normal puberty. We report a case of isolated absence of adrenarche in a post-pubertal female. A review of the literature reveals no previously reported case of isolated absence of adrenarche in a postpubertal female. An investigation was understaken to evaluate the etiology of the lack of sexual hair growth in this patient. Case A 14 year-old postpubertal female presented complaining of heavy menstrual bleeding approximately four months after her first menstrual period. The patient had been previously diagnosed with a developmental delay and speech impediment by her referring physician. Further workup revealed a normal menstrual pattern, yet the physical examination was remarkable for the absence of axillary and pubic hair, as well as short stature. A complete evaluation was performed which included chromosome analysis, serum dehydroepiandrosterone sulfate (DHEA-S), androstenedione, testosterone, dihydrotestosterone (DHT), and 3-alpha androstanediol glucuronide. The serum androstenedione, testosterone, DHT, and 3-alpha androstanediol glucuronide levels were within normal limits. The DHEA-S levels were low yet adrenal function as analyzed by the Adrenocorticotropic hormone (ACTH) stimulation test was normal. Radiologic studies included pelvic ultrasound and bone age assessment with a bone age of 16 years. Skin biopsy of the mons pubis documents the presence of hair follicles. No previous or similar history has been noted in the patient's family history. Also of note, the patient is the product of a consanguineous relationship. Conclusion After review of our investigational findings, it is felt that this unique case likely represents an androgen receptor or post-receptor defect in the hair follicle.

Androstanediol glucuronide in patients with pancreatic cancer and in those with chronic pancreatitis.

The differential diagnosis between pancreatic cancer and chronic pancreatitis is extremely difficult. Beside CA19-9 level determinations, many tests have been tried with the aim to facilitate this distinction. Serum androgen levels have been used for this purpose. To further explore the value of androgen markers in differentiating pancreatic cancer from chronic pancreatitis we determined the serum levels of androstanediol glucuronide and of androgens in the two groups of patients and compared them with CA19-9 levels. A total of 25 males were entered into the study. Of these, 13 patients had pancreatic cancer and 12 chronic pancreatitis. They were comparable as to their body weight and age. Patients with pancreatic cancer had significantly lower serum testosterone, dihydrotestosterone and androstanediol glucuronide levels, but not testosterone/dihydrotestosterone ratios when compared to patients with chronic pancreatitis. Only androstanediol glucuronide and dihydrotestosterone serum concentrations had such a small overlap between the two groups that could be used for differentiation, their sensitivity and specificity being comparable to those of CA19-9 levels. The present study has shown for the first time that serum androstanediol glucuronide levels in male patients with pancreatic cancer are significantly lower than in those patients with chronic pancreatitis. Furthermore, the sensitivity and specificity of serum andorstanediol glucuronide levels which can be used to differentiate between pancreatic cancer and chronic pancreatitis are comparable to those of CA19-9.

Comparison of plasma androgen glucuronide levels after percutaneous or peroral androgen treatment in men: evidence for important splanchnic contribution to plasma 17 beta-hydroxyandrogen glucuronides.

To investigate whether glucuronides of 17 beta-hydroxyandrogens are formed mainly in peripheral tissues or in splanchnic tissues, we compared androstanediol (AD) glucuronide (ADG) and dihydrotestosterone (DHT) glucuronide (DHTG) levels as well as the ratios of glucuronides over free steroids after transcutaneous DHT gel administration to levels and ratios found after oral administration of testosterone undecanoate. Whereas DHT and AD plasma levels were much higher after transcutaneous DHT gel administration, ADG and DHTG levels as well as glucuronide/free androgen ratios were an order of a magnitude higher after oral TU. This indicates that 17 beta-hydroxyandrogen glucuronides cannot be considered specific metabolites of androgen target tissues and are formed to a large extent in the splanchnic circulation.

Physiopathology of plasma androstanediol-glucuronide

Plasma androstanediol-glucuronide (ADG) is considered by many authors to be a highly reliable parameter of peripheral androgenicity. Recently, several authors have questioned the reliability of the ADG levels as a parameter of androgenicity. Our data obtained by continuous infusion experiments showed that in women the adrenal steroids, dehydroepiandrosterone sulfate, androstenedione and dehydroepiandrosterone are the major precursors of plasma ADG, accounting for almost the totality of circulating ADG. As expected, in view of its precursors, ADG levels decrease significantly with age. Dexamethasone causes a significant decrease of these levels, whereas in women with Addison's disease the levels are only 20% of normal levels; ovariectomy hardly influences ADG levels. Our data show that in women with moderate hirsutism, plasma ADG levels are no more often increased than the other androgens. In virilizing syndromes ADG levels are higher than expected from precursor levels, suggesting an increased 5α-reductase activity. In hyperthyroidism as well as in euthyroid women with isolated suppressed thyroid stimulating hormone, ADG levels are increased without any sign of virilism. In men, ADG levels have testosterone as a major precursor, but the adrenals contribute to ±30% of ADG levels. After transdermal dihydrotestosterone gel, free androstanediol levels increased by a factor of 40, but ADG levels were only increased by a factor of 4, suggesting that the skin is not very effective in conjugating androstanediol. It is concluded that ADG levels in women reflect essentially adrenal precursor levels as well as 5α-reductase activity in peripheral tissues inclusive of the liver.

Is plasma 5α-androstane 3α, 17β-diol glucuronide a biochemical marker of hirsutism in women?

We investigated whether plasma androstanediol glucuronide (ADG) levels reflect the increased androgenicity in women with idiopathic hirsutism ( n = 24) or hirsutism associated with polycystic ovary syndrome ( n = 10). We also evaluated whether ADG levels parallel the clinical evolution of the hirsutism during a combined treatment, with cyproteroneacetate (2 mg) and ethinylestradiol (35 μg), of women with moderate idiopathic hirsutism. Finally, we investigated if there is evidence for increased conversion of precursors to ADG in hirsutism, by comparing the ADG levels, measured by RIA, to ADG levels obtained by applying the conversion rates of precursors obtained in non-hirsute women. ADG levels were increased in less than half of the patients with mild hirsutism. The clinical cure of hirsutism, which was obtained by the treatment in majority of patients, was accompanied by a significant decrease of plasma ADG levels, but a similar decrease was also observed in the 5 patients who did not respond to treatment. The data show that, although there is evidence for increased conversion of precursors to plasma ADG in mildly hirsute women, the latter is not a reliable parameter of androgenicity. Our data suggest, moreover, that treatment with cytoproterone acetate and ethinylestradiol decreases 5α-reductase activity, as indicated by the more important decrease in ADG levels than in the precursors.

Monthly cyproterone acetate in the treatment of hirsute women: clinical and laboratory effects

Cyproterone acetate given as a single intramuscular dose of 300 mg monthly for 6 months resulted in significant reduction of hirsutism without appreciable side effects. This regimen resulted in decreased levels of luteinizing hormone (LH) and estradiol in the eight women studied. No significant changes were observed in total serum testosterone (T) levels, however, there was a reduction in sex hormone binding globulin (SHBG), resulting in lowered SHBG-bound T, and an increase in non-SHBG-T over this time. Serum androstanediol glucuronide levels decreased in three of four women, although not to normal levels.

Precursors of plasma androstanediol- and androgen-glucuronides in women

Although androstanediol (AD) and androstanediolglucuronide (ADG) are generally considered to be parameters of peripheral androgen action, their plasma levels do not always vary in parallel, suggesting that they may have different precursors. Few hard data being available concerning ADG precursors in women, we studied in postmenopausal women with absent or suppressed adrenal function, the blood conversion rates of testosterone (T), dihydrotestosterone (DHT), androstenedione (A) and dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) to AD and ADG respectively, as well as the conversion of AD to ADG. Moreover conversions of these precursors to testosteroneglucuronide (TG) and dihydrotestosteroneglucuronide (DHTG), respectively, were also studied. Our data show that, whereas plasma A and DHT are the major precursors of AD, plasma DHEAS and A are the major precursors of plasma ADG, accounting for 50 and 15%, respectively, of plasma ADG, A being the major precursor of plasma TG and DHTG, respectively. When the conversion rates, obtained in this study, were applied to the plasma concentration of precursors found in normal young and postmenopausal women, respectively, the calculated concentration of product steroids accounted for almost the totality of the actual plasma levels of ADG, TG and DHTG respectively. The difference in relative importance of their precursors, explains that plasma concentrations of AD and ADG do not always vary in parallel; moreover, the importance of DHEAS as precursor of ADG explains the suppression by dexamethasone and the increase after adrenocortical stimulation of plasma ADG levels.