Perfil androgénico en mujeres hirsutas: Modificaciones de sus niveles en la fase lútea / Androgenic profile in hirsute women: Modifications of the levels in lutheal phase

Introducción: El objetivo de este estudio fue evaluar Los niveles de Testosterona (T), T libre TL, DHEAs y Androstanodiol glucuronidato (A2G) mujeres hirsutas con ciclos menstruales (CM) regulares en la fase folicular (FF) y en una muestra tomada entre -5 a -10 días premenstrual (FL) a los efectos de 1) poder definir bioquímicamente el tipo de hirsutismo y 2) determinar si el aumento de Progesterona modifica los niveles de los andrógenos. Materiales y Métodos: En 65 mujeres hirsutas con CM regulares se determinó en FF los niveles de T, A2G, y DHEAs por RIE y TL calculada por la ecuación de la ley de acción de masas, y en la FL los niveles de P4. En 28 de las 65 pacientes, en la FL se repitió el perfil androgénico Resultados: Los niveles de T correlacionaron, en todos los casos, con los de TL. En 51 de las pacientes los niveles de P4 fueron ovulatorios, 25 de las cuales tuvieron normales los andrógenos evaluados (Hirsutismo Idiopático) De las 26 pacientes restantes, en 2 tenían T aumentada, en 4 la DHEAS. Se obtuvieron 2 parámetros aumentados en los siguientes casos; en 2 la DHEAs y el A2G, en 1 la T y la DHEAs y en1 la T y el A2G. En 4 pacientes se obtuvieron incremento de los 3 parámetros. Estas pacientes corresponden a Hiperandrogénicas ovulatorias. Las 12 restantes de estas 26 hirsutas tenían solamente el A2G aumentados. Dado que éste constituye la expresión periférica de la 5alfa reductasa, las mismas podrían incluirse en el grupo de hiperandrogénicas ovulatorias por aumento local de DHT. En 14 de las 65 pacientes los niveles de P4 fueron compatibles con ciclos anovulatorios correspondiendo a pacientes con Síndrome de Ovario Poliquístico (SOP). En 6 de ellas se constató aumento de 1, 2 o los 3 parámetros evaluados (SOP hiperandrogénicos), en las restantes 6 pacientes los niveles androgénicos fueron normales (SOP con hirsutismo clínico). El A2G aumentó significativamente en FL en las mujeres con ciclos ovulatorios (4.89±2.19 vs 3.36±2.38 ng/ml en FL y FF, respectivamente). En las anovulatorias las diferencias no fueron significativas (4.32±3.16 vs 4.69±4.54 ng/ml en FL y FF, respectivamente. Estos resultados indican que la P4 podría inducir un incremento del A2G. Dado que la T no se modificó en la FL respecto a FF (0.28±0.22 vs 0.30±0.25ng/ml en hirsutas ovulatorias y 0.47±0.32 vs 0.42±0.23 en hirsutas anovulatorias) es posible que la P4 aumente el A2G por un camino distinto a la de la T y DHT Conclusiones: En base a estos resultados podemos concluir que la determinación de A2G podría ser empleada como parámetro complementario en el estudio del hiperandrogenismo debiendo realizarse en FF dado que en FL podría ser el resultado del metabolismo de hormonas no androgénicas.

Introduction: The aim of the present study was to evaluate the circulating levels of Testosterone (T), free T (TL), DHEAs and Androstanediol glucuronide (A2G) in hirsute women with regular menstrual cycles (CM) in follicular phase (FF), and in a samples obtained 5 to 10 days before the next menstrual bleeding (FL), in order to 1) biochemically define type of hirsutism and 2) determine whether the increase in progesterone (P4) induces changes in androgen levels. Materials and Methods: Sixty five hirsute women with regular CM were studied. FF levels of T, A2G and DHEAs were determined by RIA, and TL by mass law calculation. FL levels of P4 were measured by RIA. In 28 of the 65 patients the androgen profile was also evaluated in FL. Results: The levels of T correlated in every case with those of TL. In 51 patients P4 levels were ovulatory. Twenty five of them showed normal androgen levels (Idiopathic hirsutism). From the remaining 26 patients, 2 had increased T, and 4 had increased DHEAs. Two parameters were found increased in the following cases: DHEAs and A2G in 2, T and DHEAs in 1, and T and A2G in 1. All the 3 parameters were found increased in 4 cases. These patients were ovulatory hiperandrogenic women. The remaining 12 of these 26 hirsute women had only A2G increased. Since this steroid is the peripheral expression of the 5alpha reductase activity, these women could be included in the ovulatory hiperandrogenic group because of a local increase in DHT. In 14 of the 65 patients the levels of P4 correlated with anovulatory cycles corresponding to Polycystic Ovarian Syndrome (SOP). In 6 of them an increase of 1, 2 or the 3 parameters were observed (Hiperandrogenic SOP); in the remaining 6 patients androgen levels were normal (SOP with clinical hirsutism). FL A2G significantly increased in women with ovulatory cycles (4.89±2.19 vs 3.36±2.38 ng/ml in FL and FF, respectively. Differences were no significant in the anovulatory patients (4.32±3.16 vs 4.69±4.54 ng/ml in FL and FF, respectively. These results indicate that P4 could induce an increase in A2G. Since T did not change in FL respect to FF (0.28±0.22 vs 0.30±0.25ng/ml in ovulatory hirsute and 0.47±0.32 vs 0.42±0.23 in anovulatory hirsute) it is possible that P4 increases A2G through a pathway different than that of T and DHT. Conclusions: Based on these results we conclude that A2G could be used as a complementary parameter in the study of hiperandrogenism, only in FF since in FL, it could be the result of the metabolism of non-androgenic hormones.

Altered luteinizing hormone pulsatility in infertile patients with idiopathic oligoasthenozoospermia.

In a previous study, we demonstrated that oligoasthenozoospermic (OAZ) patients had two types of testosterone response to human chorionic gonadotrophin (HCG) administration: group 1 (OAZ-1) had an altered, monophasic (no first peak) response, and group 2 (OAZ-2) had a normal biphasic response. The objective of the present work was to study the luteinizing hormone (LH) pulsatility in OAZ-1 compared with both OAZ-2 and men of proven fertility (PF), in order partly to determine the possible aetiology of the blunted acute testosterone response to HCG in these patients. LH pulsatility was measured in 10 PF, 10 OAZ-1 and 10 OAZ-2 patients, in blood samples taken every 5 min for 6 h in PF, and for 4 h in OAZ patients. LH values were determined by a time-resolved immunofluorometric assay. Frequency and amplitude of the LH pulses were determined by a computer program. LH pulse frequency, expressed as pulses/4 h, was significantly lower in OAZ-1 (1.5+/-0.97) than in PF (2.4+/-0.63) and OAZ-2 (2.4+/-0.84) patients. In six OAZ-1 and two OAZ-2 patients, LH pulsatility was diminished, as they showed less than two pulses/4 h. No statistically significant differences in LH pulse amplitude were found. These results, together with a higher number of OAZ-1 cases found with decreased LH pulsatility, suggest that, at least in a subset of these men, quantitative and/or qualitative alterations of LH secretion might have occurred.

Altered testicular hormone production in infertile patients with idiopathic oligoasthenospermia.

We studied the kinetics of testicular response to human chorionic gonadotropin (hCG) in oligoasthenospermic and asthenospermic patients (OAZ-AZ). The responses of testosterone (T), androstenedione (A), 17 OH-progesterone (17OHP), and estradiol (E2) were evaluated in 60 OAZ-AZ patients and compared to those of 10 normal men. The responses of T, A, and 17OHP to hCG in the control group displayed a biphasic pattern with an initial peak at 4 hours and a second peak after 24 hours. The E2 response showed a single peak between 24 and 48 hours after hCG administration. OAZ-AZ patients had two types of T responses: group 1 (n = 40) had no first peak and group 2 (n = 20) had a normal response pattern. The response of A was similar to that of T, and the E2 response was normal in both groups. There were three types of 17OHP responses in group 1 (low, high, or normal); however, the 17OHP response was normal in group 2. Treatment of group 1 with aromatase inhibitors (aminoglutethimide or testolactone) induced an improvement of the acute T response only in patients with high or normal 17OHP response to hCG, whereas no effects were observed in patients with low 17OHP response. In group 2, the aromatase inhibitors induced no changes in the T response. These results demonstrate that in some OAZ-AZ patients (group 1, blunted T response) testicular hormone production is altered. They also suggest the presence of two enzyme blocks: one at the 17,20 desmolase level, mediated by E2, and another at early biosynthetic steps, not mediated by E2.