Clomiphene citrate treatment for late onset hypogonadism: rise and fall

ABSTRACT Objective: Previous series have demonstrated that Clomiphene Citrate (CC) is an effective treatment to increase Total Testosterone (TT) in Late Onset Hypogonadism (LOH) patients. However, what happens to TT levels after ending CC treatment is still debatable. The objective of this study is to evaluate TT levels 3 months after the discontinuation of CC in patients with LOH who were previously successfully treated with the same drug. Materials and Methods: Twenty-seven patients with LOH that were successfully treated (achieved TT levels >11nmol/l) with CC 50mgs daily for 50 days were prospectively recruited in our Andrological outpatient clinic. CC was then stopped for 3 months and TT levels were measured at the end of this period. Results: Mean TT level before discontinuation of CC was 22.7±8.1nmol/L (mean±SD). Three months after discontinuation, mean TT level significantly decreased in all patients, 10.2±3.9nmol/l (p<0.01). Twenty-one patients (78%) decreased TT levels under 11nmol/L. Six patients (22%) had TT levels that remained within the normal recommended range (≥11nmol/l). No statistical significant differences were observed between both groups. Conclusion: In the short term LOH does not seem to be a reversible condition in most patients after CC treatment. More studies with longer follow-up are needed to evaluate the kinetics of TT in LOH.

De Sanctis-Cacchione Syndrome in a female infant - Case report / Sindrome de De Sanctis-Cacchione em lactente do sexo feminino - Relato de caso

The De Sanctis-Cacchione Syndrome is the rarest and most severe kind of xeroderma pigmentosum, characterized by microcephaly, hypogonadism, neurological disorders, mental and growth retardation, with very few cases published. The clinical findings compatible with De Sanctis-Cacchione Syndrome and the therapeutic approach used to treat a one year and nine months old child, with previous diagnosis of xeroderma pigmentosum, are reported.

A síndrome de de Sanctis-Cacchione é a forma mais rara e grave do xeroderma pigmentoso e é caracterizada por microcefalia, hipogonadismo, alterações neurológicas e retardo mental e de crescimento, com poucos casos publicados. Relatam-se os achados clínicos compatíveis com essa síndrome e a terapêutica instituída em uma lactente de um ano e nove meses, com diagnóstico prévio de xeroderma pigmentoso.

Hypogonadotropic Hypogonadism Revisited

Impaired testicular function, i.e., hypogonadism, can result from a primary testicular disorder (hypergonadotropic) or occur secondary to hypothalamic-pituitary dysfunction (hypogonadotropic). Hypogonadotropic hypogonadism can be congenital or acquired. Congenital hypogonadotropic hypogonadism is divided into anosmic hypogonadotropic hypogonadism (Kallmann syndrome) and congenital normosmic isolated hypogonadotropic hypogonadism (idiopathic hypogonadotropic hypogonadism). The incidence of congenital hypogonadotropic hypogonadism is approximately 1-10:100,000 live births, and approximately 2/3 and 1/3 of cases are caused by Kallmann syndrome (KS) and idiopathic hypogonadotropic hypogonadism, respectively. Acquired hypogonadotropic hypogonadism can be caused by drugs, infiltrative or infectious pituitary lesions, hyperprolactinemia, encephalic trauma, pituitary/brain radiation, exhausting exercise, abusive alcohol or illicit drug intake, and systemic diseases such as hemochromatosis, sarcoidosis and histiocytosis X. The clinical characteristics of hypogonadotropic hypogonadism are androgen deficiency and a lack/delay/stop of pubertal sexual maturation. Low blood testosterone levels and low pituitary hormone levels confirm the hypogonadotropic hypogonadism diagnosis. A prolonged stimulated intravenous GnRH test can be useful. In Kallmann syndrome, cerebral MRI can show an anomalous morphology or even absence of the olfactory bulb. Therapy for hypogonadotropic hypogonadism depends on the patient's desire for future fertility. Hormone replacement with testosterone is the classic treatment for hypogonadism. Androgen replacement is indicated for men who already have children or have no desire to induce pregnancy, and testosterone therapy is used to reverse the symptoms and signs of hypogonadism. Conversely, GnRH or gonadotropin therapies are the best options for men wishing to have children. Hypogonadotropic hypogonadism is one of the rare conditions in which specific medical treatment can reverse infertility. When an unassisted pregnancy is not achieved, assisted reproductive techniques ranging from intrauterine insemination to in vitro fertilization to the acquisition of viable sperm from the ejaculate or directly from the testes through testicular sperm extraction or testicular microdissection can also be used, depending on the woman's potential for pregnancy and the quality and quantity of the sperm.

Racial differences in hypogonadal improvement and prostate-specific antigen levels in hypogonadal men treated with testosterone replacement therapy

PURPOSE: To observe hypogonadal men undergoing testosterone replacement therapy (TRT) and assess racial differences in hypogonadal improvement and prostate-specific antigen (PSA) levels. MATERIALS AND METHODS: In a retrospective analysis, 75 hypogonadal men were followed for an average 34 months after initiating TRT. Total testosterone and PSA levels were assessed every 6 months, and patients diagnosed with prostatitis or prostate cancer during treatment were excluded. RESULTS: For 16 African American men, the average age at diagnosis of hypogonadism was 53.5 years, compared with 57.8 years in 59 Caucasian men (p = NS). Pre- and post-treatment testosterone was 219 ng/dL and 310 ng/dL in African American men, and 247 ng/dL and 497 ng/dL in Caucasian men (p = NS). Symptomatic response was 81 percent in African American men and 93 percent in Caucasian men (p = NS). Baseline PSA level was 1.32 ng/mL in African American men and 1.27 ng/mL in Caucasian men, and there was no significant difference in PSA between racial groups at 6-month intervals, although there was a small decreasing trend in the PSA of African Americans compared with Caucasians. CONCLUSIONS: Hypogonadal African American men have a similar normalization of testosterone and symptomatic response as hypogonadal Caucasian men, and PSA levels remain stable over time in both groups. In this hypogonadal cohort, in contrast to studies of eugonadal men, higher PSA levels in African Americans were not observed.

Predictors of successful conception in a clinical trial of 30 patients with primary amenorrheic hypogonadotrophic hypogonadism treated by ovulation induction

A clinical trial was designed to assess the association between the treatment of infertile females with Hypogonadotrophic Hypogonadism and their fertility state considering conception as the desired outcome. Serum hormones, LH, FSH and estradiol, endometrial thickness and count of active ovarian follicles were assessed by U/S to evaluat their role in anticipating a successful conception. Standard protocols of ovulation induction were used in a clinical trial [historical cohort design] of 30 patients with primary hypogonadotrophic hypogonadism. For ethical reasons no attempt was made to fix the number of induction courses given to the female patient [such a variability is suspected to confound the result to a limited extent], so a female was followed up with several courses of ovulation induction [according to the advice of the physician in charge] for a median duration of I year with conception as the final outcome of interest. Four serum hormonal markers [FSH, LH, Prolaction and estradiol] were assessed before and 12-14 days after initiating therapy. Transvaginal U/S was done to measure endometrial thickness and the number of dominant follicles in both ovaries after 12-14 days of treatment. Serum estradiol concentration, endometrial thickness and number of dominant follicles were significant predictors of successful conception. Using endometrial thickness as a decision rule to predict successful conception at a cutoff value of 7 mm, considering the rule as positive if equal or greater than 7 mm, resulted in a positive predictive value [PPV] of 50% [Relative risk of having conception was 4.3 times]. The confidence in a positive rule was increased to 71.4% [PPV =11.4%] when the cutoff value was set higher at 8 mm endometrial thickness. Using the number of dominant follicles as a decision rule at a cutoff value of 4 resulted in a PPV of 60%. This PPV was further increased to 72.7%] when the cutoff value was set higher at 5. An U/S finding of 5 or more dominant follicles increased the.probability of having conception by 12.6 times. A serum estradiol concentration at day 12 of 114 pgm/ml and higher predicted successful conception with a PPV of 50% [relative risk of having conception was 7], increasing this cutoff value of serum estradiol to a maximum of 498.5 pgm/ml increased the PPV to 66.7%. a clinician can predict successful conception after the first 2 weeks of initiating therapy with a moderate degree of confidence depending on serum estradiol, endometrial thickness and number of dominant follicles in the ovary. Other factors however need to be considered to increase the confidence of prediction, such as the type of insemination technique, sperm count of husband. A larger sample size and a survival analysis design is needed to assess the exact risk of having conception after each course of treatment

A concomitant decrease in cortical and trabecular bone mass in isolated hypogonadotropic hypogonadism and gonadal dysgenesis

To assess the impact of hypogonadism on bone mineral density, we performed a cross-sectional study of 70 amenorrheic women, comprising 22 cases of gonadal dysgenesis and 48 cases of isolated hypogonadotropic hypogonadism (IHH). Bone mineral density was measured by DEXA at four sites: the femur neck, Ward's triangle, trochanter, and lumbar spine (L2-4). The results were compared to those of a control group consisting of 60 age-matched, normal-cycling women. Bone mineral densities around age 20 were already significantly lower at all four sites in patients with IHH and gonadal dysgenesis when compared with controls, suggesting that these patients failed to achieve peak bone mass during pubertal development. In patients with IHH, the initial BMD around age 18-20 were significantly lower at all four sites and the decrease in bone density continued rapidly during the early twenties up to age 25, and then it slowed markedly thereafter. Bone biochemical marker, ICTP and osteocalcin were significantly negatively correlated with age and remained increased until age 40, which was reminiscent of menopausal bone loss pattern such as high bone turn-over in the early twenties, followed by slow bone loss in the late twenties. In patients with gonadal dysgenesis, bone biochemical marker, ICTP and osteocalcin were also significantly negative correlated with age and remained increased until age 40, but no significant changes in BMD were noted as a function of age, which may be attributed to the small sample size and slow bone loss. These findings suggest that the initiation of prompt and timely therapeutic intervention as early as possible in the menarchal period and throughout the remainder of life, particularly during the period associated with rapid bone loss.

Hipogonadismo Masculino: Un Enfoque Sencillo y Práctico / Male Hipogonadism: A Simple and Practical Approach

El hipogonadismo masculino representa una diminución de la función testicular con una baja en la producción de testosterona e infertilidad. Puede ser ocasionado por un problema intrínseco de los testículos (hipogonadismo primario), una falla del eje hipotálamo-hipofisiario (hipogonadismo secundario) o una respuesta disminuída o ausente de los órganos blanco a los andrógenos (resistencia androgénica). Los síntomas del hipogonadismo incluyen la caída del vello corporal, disminución de la función sexual y cambios de la voz. Dependiendo de la edad de aparición puede presentarse atrofia testicular, hábito eunocoide y ginecomastia. A largo plazo puede presentarse osteoporosis. El diagnóstico se sospecha clínicamente y se establece con la demostración de concentraciones bajas de testosterona sanguínea. Si existe un aumento concomitante de las gonadotropinas circulantes, Hormona Folículo Estimulante y Hormona Luteinizante, se habla de un hipogonadismo primario; pero si ambas están disminuidas el hipogonadismo es secundario. Existen diferentes formas de testosterona para el tratamiento de los pacientes con hipogonadismo; la más común, es la testosterona de depósito (enantato o cipionato) la cual se inyecta por vía intramuscular. La terapia actual consiste en la administración de testosterona por vía transdérmica, no escrotal, obteniéndose una concentración normal de testosterona con preservación del ritmo cardíaco

Uso de hormona de crecimiento en pacientes con hipogonadismo hipogonadotrófico post-quirúrgico, resistente al uso de gonadotrofinas / Use of growth hormones in patients with postsurgical hypogonadotrophic hypogonadism, gonadotrophins resistent

Se presenta el caso clínico de una paciente de 40 años, portadora de hipogonadismo hipogonadotrófico secundario a la resección transfenoidal de un prolactinoma efectuado en 1983. A pesar de múltiples intentos (10-12) de inducir ovulación con el uso de gonadotrofinas menopáusicas humanas, esto no se logró. En abril de 1995 se adicionó a las gonadotrofinas, hormona de crecimiento en dosis bajas, consiguiéndose ovulación pero no embarazo. En octubre de 1995, en el segundo intento, se consigue embarazo, que cursa normalmente

Hypogonadismes masculins: a propos de 6 observations

Six observations privilegiees d'hypogonadismes masculins ont ete retenues en une annee de consultation de Medecine Interne. Dans la majorite des cas; la symptomatologie fonctionnelle orientait vers la sphere genitale. Le bilan complementaire associant l'exploration de la fonction testiculaire; hypophysaire et des radiographies de la selle turcique a permis de noter une diversite d'etiologies (3 cas de tumeurs hypothalamo-hypophysaires; 1 syndrome de MORSIER KALLMAN et 2 cas de destruction testiculaire). A partir des observations personnelles; les auteurs proposent a la lumiere de la litterature la demarche diagnostique et therapeutique devant les hypogonadismes masculins