Assessment of Quality of Life During Gonadotrophin Treatment for Male Hypogonadotrophic Hypogonadism

Koji Shiraishi; Shintaro Okal Hideyasu Matsuyama

Disclosures

Clin Endocrinol. 2014;81(2):259-265. 

In This Article

Results

Of the 41 patients, 37 patients who completed our 24-month protocol were analysed. Because of moving (two patients) and financial problems (two patients), four patients were excluded from this study. Although we basically recommended gonadotrophin treatment, six patients underwent testosterone enanthate treatment because of financial problems and/or reluctance of self-injection. The patients' backgrounds and treatment outcomes of 31 patients who underwent gonadotrophin treatment are shown in Table 1. None of the patients received any hormonal treatment before admission. The mean age of patients who underwent hCG/rhFSH treatment was 26·8 ± 8·5 years old (range; 16–52 years). Nineteen patients were diagnosed with primary MHH, including the following: 10 idiopathic cases, four cases of paediatric pituitary surgery, three cases of Kallmann syndrome and two cases of pituitary ischaemia during delivery. Twelve patients exhibited secondary MHH: eight cases of pituitary surgery with or without radiation; three cases of other brain tumours, including pineal tumours with radiation; and one case of idiopathic adult-onset MHH. Of the 12 patients with secondary MHH, four received growth hormone, seven received thyroid hormone, and six received mineral corticoid replacements because of growth retardation, thyroid or adrenal insufficiency. There was no significant difference in the genital development and spermatogenesis between the patients with and without these comorbidities. The levels of pubic hair and genital stage in the primary cases were significantly lower than the secondary cases (P < 0·05, respectively, Table 1). After gonadotrophin treatment, the average testicular volume increased twofold, and all of the patients exhibited Tanner stage 3 or higher genitals in both primary and secondary cases. The average serum testosterone level was 5·3 ± 1·8 ng/ml. There was no significant difference in the testosterone levels before and after the treatment between primary and secondary cases. Twelve patients underwent semen examinations before treatment and 10 patients (83%) exhibited azoospermia and two secondary MHH patients exhibited cryptozoospermia. Twenty-four (77%) patients underwent semen examinations during the treatment periods, and 21 (88%) observed sperm or an increased number of sperm in their ejaculate. The mean sperm concentration was 12·4 × 106/ml, and the mean sperm motility was 57·1%. The average time to observe sperm in the ejaculate was 16·3 months (primary case: 17·4 months, secondary case: 13·8 months). In the case of pretreatment cryptozoospermia or severe oligozoospermia, the maximum sperm concentration was 23·5 × 106/ml or 18·6 × 106/ml; therefore, these cases were categorized as improvements in spermatogenesis. The average semen volume was also significantly increased after gonadotrophin treatment. There was no significant difference in semen volume and spermatogenesis between primary and secondary cases. Mean haemoglobin increases of gonadotrophin or testosterone treatment were of 2·4 or 1·8 g/dl, respectively, but no patients stopped the hormonal therapy. Gynaecomastia was noted in five cases (16%) without any treatment. Three patients were married during the follow-up period (2 idiopathic cases and 1 postpituitary surgery), and two patients were able to conceive children naturally. One patient who was treated from 24 years old continues to keep normal gonadotrophins and testosterone levels 1 year after discontinuation.

The patients' backgrounds and treatment outcomes of 6 patients who underwent testosterone treatment are shown in Table 2. There was no difference in the development of genitalia compared with gonadtrophin treatment. All the patients who could ejaculate showed azoospermia.

The figure demonstrates the changes in each of the SF-36 domains during gonadotrophin or testosterone treatments. Both gonadotrophin and testosterone treatments significantly improved the PF domain after 12 months (P < 0·05, Fig. 1a). In the RP domain, significant improvements were observed after 12 and 24 months by gonadotrophin or testosterone treatments, respectively (P < 0·05, Fig 1b). BP and SF were not involved in the HRQOL of MHH patients (Fig.1c and f). In the GH and RE domains, large increases, up to normal values, were observed at 24 months by gonadotrophin, but not testosterone treatment (P < 0·001, P < 0·01, respectively, Fig. 1d and g). Similarly, in the VT and MH domains, large increases, up to normal values, were observed from 18 months by gonadotrophin, but not testosterone treatment (P < 0·01, Figure 1e and h). There was no significant difference in the improvement of SF-36 scales between primary and secondary cases. Table 3 presents the associations between patient factors and improvement in the SF-36 domains that exhibited significant improvement (PF, RP, GH, VT, RE and MH), calculated as follows: (crude post-treatment point) – (crude pretreatment point). There were no associations between improvement and patient age, final testicular volume or final serum testosterone concentration and no differences in improvement categorized by cause, pubic hair stage or genital stage. In patients who could ejaculate, the improvement in VT was significantly greater than in those who could not ejaculate (P < 0·05). In patients who could observe sperm in their ejaculate, the improvements in GH, VT, RE and MH were significantly greater than in those who could not observe sperm (P < 0·05). There were the same tendencies if the patients were subdivided by primary and secondary MHH.

Figure 1.

The changes of SF-36 subdomains in patients treated with gonadotrophins (closed square) or testosterone (closed circle). Values during the treatment period were compared with pretreatment value by paired t-test. NBS: norm-based scores of gonadotrophin treatment group. *P < 0·05, **P < 0·01, ***P < 0·001.

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