- 04-24-2007, 07:50 PM
- 04-25-2007, 10:32 AM
thanks for posting this griffinannie, i was going to ask about this myself. I can't seem to find any information on it anywhere. I am looking to run this alongside HCG to stimulate testicular regrowth/function.
What is this stuff called in medication terms? Does it have a brand, etc?
04-25-2007, 11:12 AM
I have an apt. with my specialist in a months time and plan to ask him to allow me to run a HMG/HCG/Nolvadex Comboin an effort to increase my total testosterone. Here are a few studies I have accumulated so far that I plant to show the doc...Hope this helps
L Liu, SM Banks, KM Barnes and RJ Sherins
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892.
Men with the complete form of isolated hypogonadotropic hypogonadism (initial mean testes volume less than 4 mL) require 2 or more yr of exogenous gonadotropin therapy combining hCG and human menopausal gonadotropin (hMG) to achieve maximal, but subnormal, testis size and sperm output. To test whether pulsatile GnRH therapy, which more closely mimics normal hormonal stimulation, would accelerate or further augment testicular growth, hasten the onset of sperm production, and/or increase sperm output more than occurs during conventional exogenous gonadotropin therapy, we administered either hCG/hMG or GnRH from the inception of therapy to 2 comparable groups of men with complete IHH (initial testicular volume, less than 4 mL) and compared their testicular responses during the first 2 hr of therapy. Five men were treated with pulsatile GnRH in doses of 143-714 ng/kg every 2 h, sc, while 11 other men received hCG (2000 IU) and hMG (75 IU FSH and 75 IU LH) im 3 times/week. In the GnRH-treated men, the mean plasma total and free testosterone levels during therapy rose to within the normal range, but were significantly lower (P less than 0.01 and P less than 0.02, respectively) than those in the hCG/hMG-treated men. The mean plasma estradiol concentrations during therapy were within the high normal range and were similar in the two groups. The mean plasma FSH levels achieved in the GnRH-treated men were significantly (P less than 0.01) and 1.3- to 3.2-fold higher than those in the hCG/hMG-treated men. The mean testicular size achieved in the GnRH-treated men was not significantly different from that in the hCG/hMG-treated men (P = 0.08); the mean testicular volumes after 2 yr were 4.8- and 4.3-fold the pretreatment values in the GnRH and hCG/hMG groups, respectively. After 12 months of therapy, sperm production had occurred in one man in the GnRH group and in no subject in the hCG/hMG group. After 24 months, two men in the GnRH group and eight men in the hCG/hMG group produced sperm. Thus, 40% of the GnRH-treated men and 80% of the hCG/hMG-treated men (P = NS) produced sperm after 2 yr of therapy. The sperm concentrations in all men were below 5 million/mL and were comparable in the two groups (P = NS). These results suggest that pulsatile sc GnRH therapy for the first 2 yr does not accelerate or enhance testicular growth, hasten the onset of sperm production, or increase sperm output significantly compared to hCG/hMG. "
Journal of Clinical Endocrinology & Metabolism, Vol 61, 746-752, Copyright © 1985 by Endocrine Society
Male hypogonadotropic hypogonadism: factors influencing response to human chorionic gonadotropin and human menopausal gonadotropin, including prior exogenous androgens
SB Ley and JM Leonard
Although testosterone (T) therapy is sufficient for maturation and maintenance of secondary sex characteristics in hypogonadal men, gonadotropins are required for stimulation of spermatogenesis. Thirteen men with hypogonadotropic hypogonadism received treatment with hCG, followed in 12 by the addition of human menopausal gonadotropin (hMG). All initially had undetectable serum LH and FSH and low T levels and were azoospermic with small testes. During therapy, all achieved normal male levels of T. Twelve of 13 had marked and continuous increase in testicular volume. Three men had sperm in the ejaculate with hCG treatment alone. All but 1 patient developed sperm in their seminal fluid during combined hCG and hMG therapy. Two men achieved three pregnancies, and 2 more had semen that produced hamster oocyte penetration assays in the fertile range during the protocol period. Four of 5 who achieved sperm densities greater than 1 million/ml while receiving combined therapy maintained or increased sperm production while receiving continued hCG therapy after hMG was withdrawn. We examined the response to gonadotropin therapy of men who had received previous T therapy and those who had not. There were no differences in rapidity or degree of response, as assessed by rise in serum T, increase in testis volume, or maximal sperm density achieved. Multiple pituitary deficits and cryptorchidism were negative prognostic factors. In summary, the prognosis for successful stimulation of spermatogenesis in men with hypogonadotropic hypogonadism treated with hCG/hMG is good and not adversely affected by prior androgen treatment. Despite undetectable serum FSH levels, hCG treatment was sufficient to both initiate and maintain spermatogenesis in some patients.
Jones TH, Darne JF.
University of Sheffield, Department of Medicine, UK.
OBJECTIVE: We determined whether or not self-administered subcutaneous human menopausal gonadotrophin (hMG) therapy is safe and effective in the stimulation of testicular growth and initiation of spermatogenesis in men with hypogonadotrophic hypogonadism where human chorionic gonadotrophin alone had failed. DESIGN: Human menopausal gonadotrophin was self-administered subcutaneously in two dosage regimens to patients requiring (a) fertility (Group I), 37.5 IU twice daily (total weekly dose 525 IU) (n = 7) and (b) increased testicular size (Group II) 37.5 IU once daily (total weekly dose 265.5 IU) (n = 2). Patients were assessed on a monthly basis. PATIENTS: Nine patients with hypogonadotrophic hypogonadism were studied. Six patients had idiopathic isolated hypogonadotrophic hypogonadism, one Kallman's syndrome, one idiopathic isolated hypogonadotrophic hypogonadism secondary to trauma and one with panhypopituitarism secondary to radiotherapy for a hypothalamic pituitary tumour. Five of these patients had a history of unilateral or bilateral cryptorchidism. MEASUREMENTS: Semen analysis and serum testosterone. Testicular size was assessed by use of a Prader orchidometer. RESULTS: Six of seven patients (four with a history of cryptorchidism) requesting fertility attained sperm counts of > 10 million/ml. Three pregnancies have been achieved so far. One failure occurred in a patient with a previous history of cryptorchidism. In Group I patients (a) with an initial testicular volume of 4 ml or less (n = 4), mean size increased from 3.25 +/- 0.9 (SD) ml to 12.2 +/- 3.8 ml, (b) an initial testicular volume of > 4 ml mean size (n = 3) increased from 9.2 +/- 3.9 ml to 10.3 +/- 4 ml. In Group II (n = 2) testis size increased from a mean of 3.0 +/- 1.4 ml to 9.0 +/- 1.4 ml over a 6-months treatment period. CONCLUSION: Self-administered subcutaneous human menopausal gonadotrophin is a safe and effective mode of therapy in increasing testicular size and inducing spermatogenesis in males with hypogonadotrophic hypogonadism.
Effects of Human Recombinant Luteinizing Hormone and Follicle-Stimulating Hormone in Patients with Acquired Hypogonadotropic Hypogonadism: Study of Sertoli and Leydig Cell Secretions and Interactions
Jacques Young, Beatrice Couzinet, Philippe Chanson, Sylvie Brailly, Ernest Loumaye and Gilbert Schaison
Service d’Endocrinologie et des Maladies de la Reproduction (J.Y., B.C., P.C., G.S.) and Laboratoire d’hormonologie (S.B.), Hôpital Bicêtre, 94275 Kremlin Bicêtre, France; and ARES Serono (E.L.), CH-1211 Geneva, Switzerland.
Address correspondence and requests for reprints to: Gilbert Schaison, M.D., Service d’Endocrinologie et des Maladies de la Reproduction, Hôpital Bicêtre, 94275 Kremlin Bicêtre cedex, Frace. E-mail: [email protected].
Experimental data suggest that FSH-stimulated Sertoli cells can enhance LH-induced Leydig cell testosterone (T) production. The function of Leydig and Sertoli cells can be selectively studied by using recombinant human LH (rhLH) and recombinant human FSH (rhFSH) in patients with complete gonadotropin deficiency. The aim of the present study was to assess the secretion of testicular T, estradiol (E2), and inhibin B and the physiological relevance of the Sertoli-Leydig cell interaction in man. For that purpose, six patients with acquired complete hypogonadotropic hypogonadism received the following treatments for three periods of 1 month in a random order: 1) rhLH, 900 IU/day sc; 2) rhFSH, 150 IU/day sc; and 3) combined rhLH/rhFSH treatments. Each treatment period was separated by a washout period of 15 days. Plasma LH, FSH, T, E2, and inhibin B were measured before and every 10 days during each treatment. During rhLH administration, mean plasma LH levels rose significantly from 0.4 ± 0.2 IU/L to 11.7 ± 1.2 IU/L (P < 0.01) and plasma FSH levels did not change. rhFSH administration induced a significant increase in plasma FSH levels (from 0.5 ± 0.4 to 12.1 ± 1.4 IU/L; P < 0.01), whereas mean plasma LH levels remained low. Mean plasma E2 levels were unchanged during rhFSH treatment, but they increased significantly during rhLH from 22 ± 4 to 54 ± 8 pmol/L (P < 0.01) and during rhLH plus rhFSH administration. rhFSH treatment induced a sustained elevation of mean plasma inhibin B levels from 58 ± 13 to 175 ± 25 pg/mL (P < 0.01), similar to the increase occurring during rhFSH plus rhLH administration. In contrast, mean plasma inhibin B levels did not increase during rhLH administration. Finally, a similar and significant increase in mean plasma T levels occurred during both rhLH and rhLH plus rhFSH treatment from 0.9 ± 0.3 to 5.4 ± 0.7 nmol/L (P < 0.01) and from 1.0 ± 0.4 to 6.0 ± 0.9 nmol/L (P < 0.01), respectively. In contrast, during rhFSH treatment mean plasma T levels remained unchanged when compared with baseline. In conclusion: 1) the increase of plasma E2 induced by rhLH and the absence of effect of rhFSH confirm that Leydig cells are the major site of testicular E2 production in man; 2) the secretion of inhibin B is increased by rhFSH and not by rhLH, and, thus, Sertoli cells seem to be the main source of inhibin B production; and 3) the increase of plasma T induced by rhLH is not enhanced by rhFSH. These results suggest that the stimulatory effect of FSH on Leydig cell steroidogenesis by a Sertoli cell paracrine factor does not seem to play a major physiologic role in man.
The specific physiological functions of testicular cells and the paracrine regulation of Leydig cells by Sertoli cells are difficult to study in vivo in normal man. Therefore, complete HH characterized by the absence of secretion of endogenous gonadotropins is a convenient model to assess the respective effects of LH and FSH on gonadal function. Because the Leydig cells contain only receptors for LH and the Sertoli cells contain only receptors for FSH, the use of rhLH and rhFSH enables the functions of both Leydig and Sertoli cells to be studied selectively. In the present study, using recombinant human gonadotropins, endocrine testicular function was assessed in adult men with acquired HH and hypopituitarism, but normal GH secretion. This pathological model was convenient to evaluate the specific roles of rhLH and rhFSH on Leydig and Sertoli cell function and to assess the physiological relevance of the concept that FSH can enhance testicular T production induced by LH in humans. Men with acquired HH were selected, and subjects with congenital HH or GH deficiency were excluded. In congenital HH, the absence of fetal or neonatal gonadotropin secretion may impair the development of Sertoli cells and their response to short-term FSH administration (19, 20). In patients with GH and IGF-I deficiency, testicular LH receptors and steroidogenic responsiveness may be decreased (12, 13).
The administration of rhLH (900 IU/day) alone or in association with rhFSH increased plasma LH levels similarly, to the levels observed in normal men. During rhLH treatment, low plasma FSH levels remained unchanged, as expected, with the LH recombinant preparation used in this study. During rhFSH (150 IU/day), plasma FSH levels increased but plasma LH levels did not change.
In patients with acquired HH, mean plasma E2 levels were almost undetectable. A significant and similar increase was observed during isolated rhLH treatment or combined rhLH plus rhFSH treatment. In contrast, plasma E2 levels remained low when rhFSH was administered alone. These results confirm that, in contrast to rat testis (21), the human testicular aromatase is localized within Leydig cells and not in Sertoli cells. This conclusion is in agreement with previous immunohistochemical and enzymatic studies showing that immunoreactive aromatase and aromatase activity were present only in the Leydig cells and absent from the Sertoli cells in normal adult human testes (22).
At baseline, patients with acquired HH had plasma inhibin B levels markedly below those of normal men, as reported previously, in congenital HH (8, 20). The administration of rhFSH promptly restored inhibin B levels to those observed in normal men. In contrast, rhLH treatment failed to increase immunoreactive inhibin B. These results confirm the selective FSH dependence of circulating inhibin B, as reported previously, in normal men (8). Sertoli cells seem to be the main source of inhibin B production. The finding that rhFSH treatment stimulated testicular secretion of inhibin B in these patients also demonstrated the normal functional capacity of their Sertoli cells.
As expected, in patients with acquired HH mean plasma T levels were very low. A significant increase in plasma T levels was observed during rhLH treatment. This result confirmed that the rhLH preparation used in the present study was biologically active. However, in contrast to hCG (1500 IU twice weekly), rhLH at the daily dose of 900 IU failed to restore mean plasma T levels to those observed in normal adult men. This difference was probably related to the shorter half-life and lower potency of rhLH than hCG (23, 24). Therefore, in the future, higher regimen doses will be necessary to restore normal T secretion and, in association with FSH, to achieve spermatogenesis in patients with complete HH.
The use of recombinant gonadotropins in patients with acquired HH also provided an opportunity to examine the concept that FSH may enhance the responsiveness of Leydig cells to LH. Earlier studies in support of the paracrine control of Leydig cells by Sertoli cells were conducted in rodents or in in vitro models (1, 25). In hypophysectomized immature rats, FSH treatment induced Leydig cell hyperplasia, increased the number of testicular LH receptors, and increased the steroidogenic response of Leydig cells to LH (1). In vitro, coculture of Leydig cells with Sertoli cells isolated from immature pig testis enhanced hCG-stimulated T production when compared with the response of Leydig cells cultured alone. Pretreatment of cocultures with FSH further enhanced the steroidogenic capacity of Leydig cells and induced a significant increase in the number of hCG receptors (1). Several Sertoli cell-secretory products have been identified that can potentially mediate regulatory interaction between Sertoli and Leydig cells (1, 25). Some of these (e.g. IGF-I) stimulate, but others (e.g. transforming growth factor ß) inhibit Leydig cell steroidogenesis (1). In addition, the effects of these factors on Leydig cell function may be species dependent (1).
In humans, natural mutations of FSH ß-subunit and FSH receptor genes could provide new insights into the effects of FSH and steroidogenesis in Leydig cells. However, at present, case reports are rather puzzling. In one recently reported mutation of the FSH ß gene, the affected patient had delayed puberty, selective absence of FSH, and low plasma T levels with high plasma LH levels (26). In contrast, in another case of FSH ß gene mutation, the absence of FSH and azoospermia were associated with normal puberty and normal plasma T levels (27). In agreement with this latter case report, FSH deficiency has previously been reported in men with variable degrees of spermatogenesis impairment, but with normal T production and virilization (28). Similarly, men with homozygous FSH receptor-inactivating mutations reported by Tapanainen et al. (29) had variable reduction in testis size and sperm count, but all were normally masculinized and had normal plasma T levels. Thus, naturally occurring FSH ß gene and FSH receptor gene mutations in man have not clarified the putative indirect role of FSH in adult testicular Leydig cell function.
In the present study, the increase in mean plasma T levels induced by rhLH was not enhanced by the concomitant administration of rhFSH, despite the effective stimulation of Sertoli cell function, attested by the increase in plasma inhibin B. The same result was observed with a greater increase in plasma T levels after hCG and hCG plus rhFSH administration. These results are in agreement with recent studies performed in primates (30). Indeed, in juvenile rhesus monkeys receiving a pulsatile iv infusion of GnRH, the concomitant infusion of rhFSH did not affect either the mean plasma levels of T or the amplitude of pulsatile testicular T secretion. Therefore, in man as in primates, the physiological relevance of a role of FSH in LH-induced testicular steroidogenesis seems questionable.
In conclusion, complete acquired HH and the use of rhLH and rhFSH enable the functions of Leydig and Sertoli cells to be studied selectively. Apart from peripheral aromatization of testicular T, the increase of plasma E2 induced by rhLH and the absence of an effect of rhFSH is consistent with the view that Leydig cells are the major site of testicular E2 production in man. The secretion of inhibin B, increased by rhFSH and not by rhLH, confirms that Sertoli cells are the main source of inhibin B production. Finally, the increase in plasma T induced by rhLH or hCG was not enhanced by rhFSH. These results suggest that the stimulatory effect of FSH on Leydig cell steroidogenesis by a Sertoli cell paracrine factor does not seem to play a major physiological role in man.
Received January 26, 2000.
Revised May 19, 2000.
Accepted May 24, 2000.
Effects of Human Recombinant Luteinizing Hormone and Follicle-Stimulating Hormone in Patients with Acquired Hypogonadotropic Hypogonadism: Study of Sertoli and Leydig Cell Secretions and Interactions -- Young et al. 85 (9): 3239 -- Journal of Clinica
04-25-2007, 12:22 PM
According to my fertility doc after I have been of test cyp for a month and they can run blood tests hcg\hmg is what I will probably be doing. Funny part is my wife wants me back on test also....she likes the lawn being mowed as well as other household chores ; )
Hopefully we can report back in a month or two to see how things turn out.
04-25-2007, 12:39 PM
From previous post:
"After 12 months of therapy, sperm production had occurred in one man in the GnRH group and in no subject in the hCG/hMG group. After 24 months, two men in the GnRH group and eight men in the hCG/hMG group produced sperm. Thus, 40% of the GnRH-treated men and 80% of the hCG/hMG-treated men (P = NS) produced sperm after 2 yr of therapy. "
04-25-2007, 12:59 PM
Thats doesn't sound unreasonable, thats about how long it takes an average healthy couple to be with child. Hopefully the ache in the balls will reside assuming I get test cyp again.
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