madman
Super Moderator
Background: In this study, we evaluated MHH patients who wished to preserve fertility, assessing the efficacy of a short course (12 months) of a combined hCG +clomiphene citrate.
Materials and Methods: The cross-sectional study included 19 patients with hypogonadotropic hypogonadism who were admitted to the Andrology and Fertility Hospital of Hanoi between March 2016 and March 2018. Using hCG every three days in combination with clomiphene citrate 25mg per day until normal testosterone levels are reached, maintain the dose until spermatozoa are present.
Results: The mean age was 30.2 ± 5.6. Differences in penis length between the time before and after treatment were significant (p=0.005). The average dose of hCG using in our study was 5579 ± 1773.7 IU. After treatment 6 months and 12 months, the changes in clinical features in all patients and the total hypogonadotropic hypogonadism group were statistically significant (p<0.001). In particular, the differences in testosterone hormone levels in the partial hypogonadotropic hypogonadism group were also statistically significant (p=0.03). No adverse event was observed in our study. The number of patients appearing sperm in the semen is 9 patients (47.4%) after 12 months, but most of the sperm were completely deformed (<1%), and the average motility in the progressive motility group was below 8%.
Conclusion: In conclusion, a combination of hCG and clomiphene citrate may be an option for MHH patients who desired fertility. After 12 months, 47.4% of patients have sperm in semen but almost all of them were deformities. Hormone profile and secondary sexual characteristics improved significantly. There was no adverse event in our study that considered it as safe therapy.
Introduction
Male hypogonadism is divided into hypergonadotropic and hypogonadotropic (male hypogonadotropic hypogonadism, MHH). MHH is caused by insufficient secretion of gonadotropins and can be classified into three, namely, congenital, acquired, and idiopathic. MHH presents as absent/delayed/arrested sexual maturation and infertility. It has a lower prevalence than primary hypogonadism.1 To optimize the management of MHH after confirmation of the disease and consideration of future fertility prospects, the timing and choice of therapeutic intervention are important. Therapy involves the use of testosterone to induce the development of secondary sexual characteristics, which in turn leads to puberty and to the maintenance of secondary sexual characteristics.2 Therapy is likely to be life-long and requires regular monitoring. Thus, choosing a therapy to optimize responses and avoid adverse events is essential. Testosterone can come from exogenous or endogenous sources. Testosterone replacement therapy using exogenous testosterone is good for improving the quality of life and achieving physical benefits, but this therapy is not suitable for those who are currently seeking fertility.3,4 Exogenous testosterone suppresses gonadotropin hormones in the hypothalamus-pituitary–testes axis, which is necessary for normal spermatogenesis to occur. To maintain fertility, exogenous testosterone treatment should be stopped.
Gonadotropin replacement therapy (GRT) induces both spermatogenesis and endogenous testosterone. GRT requires either pulsatile gonadotropin-releasing hormone (GnRH) or gonadotropin administration. Gonadotropins can be self-administered subcutaneously and are not inferior to the more costly GnRH.5 Human chorionic gonadotropin (hCG) injection is also an effective therapy for patients with MHH.6 The benefits of hCG treatment for MHH patients instead of testosterone were confirmed in the current review.7 Clomiphene citrate (CC), a selective estrogen receptor modulator, is being used (off-label) for testosterone deficiency and does not interfere with spermatogenesis. CC effectively increases serum testosterone with few side effects in men with testosterone deficiency8 and is safe for the long-term management of hypogonadism.9
Treatment Plan
*One of the two brands of hCG (Pregnyl®, Merck & Co., Inc or IVF-C®, LG Lifesciences) was used every 3 days, the dose depended on the response of each patient (from 3000 IU to 10,000 IU) in combination with CC at 25 mg per day until normal testosterone levels are reached. The dose is maintained until spermatozoa appeared in the semen. Supplementation with HMG or FSH was made if the patient wanted to have children, as shown in the following schema (Figure 1).
*The most important issue when using hCG to treat MHH and to achieve the desired outcomes was the dose and duration of treatment.24 In the present study, the group was treated with CC at 25 mg daily and hCG at an average dose of 5000 IU administered twice weekly (i.m. or s.c.). To support endogenous testosterone production for the period of infertility treatment, hCG treatment can be administered at the appropriate dosage to prevent serum FSH level suppression.25 In this situation, through a negative feedback mechanism, CC supported the effect of hCG and optimized the treatment.
*The hormone hCG induces testosterone production by stimulating Leydig cells directly. Its effect is similar to that of LH, but its elimination half-life is longer than that of LH, thereby avoiding the need for daily injections. The level of testicular testosterone increased, thereby inducing the onset of spermatogenesis21,26 and stimulating Sertoli cell maturation and proliferation.21,27
Conclusion
In conclusion, a combination of hCG and CC may be an option for MHH patients who desired to restore their fertility. After 12 months, 52.63% of patients showed the restoration of spermatogenesis, and spermatozoa appeared in semen. Testosterone level increased by approximately 25 times by mean and was in the normal range at 12 months after treatment. Secondary sexual characteristics improved significantly, especially the increase in body height and penile length, even in patients over 18 years old. This therapy was considered safe because no adverse event was noted.
Materials and Methods: The cross-sectional study included 19 patients with hypogonadotropic hypogonadism who were admitted to the Andrology and Fertility Hospital of Hanoi between March 2016 and March 2018. Using hCG every three days in combination with clomiphene citrate 25mg per day until normal testosterone levels are reached, maintain the dose until spermatozoa are present.
Results: The mean age was 30.2 ± 5.6. Differences in penis length between the time before and after treatment were significant (p=0.005). The average dose of hCG using in our study was 5579 ± 1773.7 IU. After treatment 6 months and 12 months, the changes in clinical features in all patients and the total hypogonadotropic hypogonadism group were statistically significant (p<0.001). In particular, the differences in testosterone hormone levels in the partial hypogonadotropic hypogonadism group were also statistically significant (p=0.03). No adverse event was observed in our study. The number of patients appearing sperm in the semen is 9 patients (47.4%) after 12 months, but most of the sperm were completely deformed (<1%), and the average motility in the progressive motility group was below 8%.
Conclusion: In conclusion, a combination of hCG and clomiphene citrate may be an option for MHH patients who desired fertility. After 12 months, 47.4% of patients have sperm in semen but almost all of them were deformities. Hormone profile and secondary sexual characteristics improved significantly. There was no adverse event in our study that considered it as safe therapy.
Introduction
Male hypogonadism is divided into hypergonadotropic and hypogonadotropic (male hypogonadotropic hypogonadism, MHH). MHH is caused by insufficient secretion of gonadotropins and can be classified into three, namely, congenital, acquired, and idiopathic. MHH presents as absent/delayed/arrested sexual maturation and infertility. It has a lower prevalence than primary hypogonadism.1 To optimize the management of MHH after confirmation of the disease and consideration of future fertility prospects, the timing and choice of therapeutic intervention are important. Therapy involves the use of testosterone to induce the development of secondary sexual characteristics, which in turn leads to puberty and to the maintenance of secondary sexual characteristics.2 Therapy is likely to be life-long and requires regular monitoring. Thus, choosing a therapy to optimize responses and avoid adverse events is essential. Testosterone can come from exogenous or endogenous sources. Testosterone replacement therapy using exogenous testosterone is good for improving the quality of life and achieving physical benefits, but this therapy is not suitable for those who are currently seeking fertility.3,4 Exogenous testosterone suppresses gonadotropin hormones in the hypothalamus-pituitary–testes axis, which is necessary for normal spermatogenesis to occur. To maintain fertility, exogenous testosterone treatment should be stopped.
Gonadotropin replacement therapy (GRT) induces both spermatogenesis and endogenous testosterone. GRT requires either pulsatile gonadotropin-releasing hormone (GnRH) or gonadotropin administration. Gonadotropins can be self-administered subcutaneously and are not inferior to the more costly GnRH.5 Human chorionic gonadotropin (hCG) injection is also an effective therapy for patients with MHH.6 The benefits of hCG treatment for MHH patients instead of testosterone were confirmed in the current review.7 Clomiphene citrate (CC), a selective estrogen receptor modulator, is being used (off-label) for testosterone deficiency and does not interfere with spermatogenesis. CC effectively increases serum testosterone with few side effects in men with testosterone deficiency8 and is safe for the long-term management of hypogonadism.9
Treatment Plan
*One of the two brands of hCG (Pregnyl®, Merck & Co., Inc or IVF-C®, LG Lifesciences) was used every 3 days, the dose depended on the response of each patient (from 3000 IU to 10,000 IU) in combination with CC at 25 mg per day until normal testosterone levels are reached. The dose is maintained until spermatozoa appeared in the semen. Supplementation with HMG or FSH was made if the patient wanted to have children, as shown in the following schema (Figure 1).
*The most important issue when using hCG to treat MHH and to achieve the desired outcomes was the dose and duration of treatment.24 In the present study, the group was treated with CC at 25 mg daily and hCG at an average dose of 5000 IU administered twice weekly (i.m. or s.c.). To support endogenous testosterone production for the period of infertility treatment, hCG treatment can be administered at the appropriate dosage to prevent serum FSH level suppression.25 In this situation, through a negative feedback mechanism, CC supported the effect of hCG and optimized the treatment.
*The hormone hCG induces testosterone production by stimulating Leydig cells directly. Its effect is similar to that of LH, but its elimination half-life is longer than that of LH, thereby avoiding the need for daily injections. The level of testicular testosterone increased, thereby inducing the onset of spermatogenesis21,26 and stimulating Sertoli cell maturation and proliferation.21,27
Conclusion
In conclusion, a combination of hCG and CC may be an option for MHH patients who desired to restore their fertility. After 12 months, 52.63% of patients showed the restoration of spermatogenesis, and spermatozoa appeared in semen. Testosterone level increased by approximately 25 times by mean and was in the normal range at 12 months after treatment. Secondary sexual characteristics improved significantly, especially the increase in body height and penile length, even in patients over 18 years old. This therapy was considered safe because no adverse event was noted.
