liftsiron
Community Veteran, Longtime Vet
Posted bt Restless on Cuttingedgemuscle
Opioid antagonists and HPTA function
I just heard about the possible effect of opioid antagonists in LH secretion in another board and went to pub med looking for studies on this hoping I could generate some discussion here.
This is the post that started this:
"Now for the most important piece of the post cycle recovery puzzle that you never hear bodybuilders talk about because they usually have no idea. The opioidergic regulation of testosterone. Without going to great lengths in explaining opioids and their effects on hormones and the brain, natural opiates are released in response to the increase in LH by the use of estrogen inhibitors. So you've got increased LH and increased natural opiate levels. Now when the estrogen inhibitors are taken away the LH is greatly reduced and you're back to square one. So your natural opiate levels are still high. LH will not be stimulated until it comes back down. That is in a sense why HCG and estrogen inhibitors are only so affective at stimulating testicular function and restoring the HPT axis. So since opiates suppress gonadotropin secretion i.e. testosterone secretion using opiate antagonists can help bodybuilders completely recover. REVIA is the most popular. Read all you can on the subject because it really is the missing link of post cycle recovery. Later!"
He doesn't provide any references so I went to check it out and did found some stuff (see below). I didn't find anything about the increase in endogenous opioids from LH increases, but I haven't searched yet (anyone knows anything about this?).
Study number found a significant impact on LH levels after naxolone treatment (in goats....).
Second one has this bit that intrigues me:
"Administration of specific opiate antagonists decreases luteinizing hormone (LH) release and increases the frequency and amplitude of the LH pulses"
If I'm not mistaken number 3 shows that naloxone is effective in stimulating LH relese in obese patients, nut not in normal individuals.
Number 4 shows a positive effect in LH and testosterone levels from two different antagonists and some stuff about LH and prolactin pulse sinchrony that is probably meaningless for our purposes.
Number 5 shows a 50% increase in cortisol. Not so good.
Number 6 shows a positive impact in sexual function even without any noticeable changes in hormone levels.
I am not sure this is actually worth trying during post cycle therapy (pct), but I'd love to hear people's opinions on this. These drugs have some unpleasant side effects but I think I'm willing to give it a try if I'm convinced there may be something to it.
Thoughts please?
1-Effect of naloxone on the plasma levels of LH, FSH, prolactin and testosterone in Beetal bucks.
Singh B, Dixit VD, Singh P, Georgie GC, Dixit VP.
Department of Animal Production Physiology, CCS Haryana Agricultural University, 125004, Hisar, India
Ten adult male Beetal goats were used for the study to elucidate the modulation of gonadotrophin, prolactin and testosterone secretion by endogenous opioid peptides. An indwelling catheter was placed in the jugular vein of each buck 20h before the onset of the experiment. Bucks were divided randomly into two groups: Group I (n=5) received naloxone at a dose rate of 1mg/kg body weight (BW) and Group II (n=5) received naloxone at a dose rate of 2mg/kg BW intravenous. Blood samplings were done from 2h before treatment until 2h after treatment at 15min intervals. Blood samples were quantified for plasma LH, FSH and prolactin concentration using a heterologous double antibody radioimmunoassay (RIA) and testosterone concentration was quantified by coat-a-count RIA kit. The mean plasma LH levels during pretreatment phase were 0.41+/-0.03ng/ml in Group I and 0.44+/-0.02ng/ml in Group II which significantly (p<0.05) increased to 0.91+/-0.05ng/ml in Group I and 1.53+/-0.07ng/ml in Group II. The mean plasma FSH levels did not show a difference in pre- and post-treatment animals in both groups. A significant (p<0.05) increase in plasma testosterone concentration was observed in both groups after naloxone treatment, whereas, a decrease (p<0.05) was observed in plasma prolactin levels after naloxone treatment. Thus, it can be concluded that endogenous opioids do play an important role in modulating plasma LH, prolactin and testosterone concentrations in male goats.
2-[Interaction of endogenous opioid peptides with the function of the hypothalamo-hypophyseal-testicular axis]
[Article in Spanish]
Pedron Nuevo N.
Unidad de Investigacion Medica en Biologia de la Reproduccion. Division de Investigacion Biomedica. IMSS, Mexico, D.F.
Since the discovery of endogenous opioid peptides and opioid receptors in the brain, their has been considerable interest in their possible role in a variety of physiological and pharmacological processes. The endogenous opioids and opiate active substances have been clearly implicated in the regulation of male reproductive function. It has been demonstrated that opioid peptides inhibit gonadotropin and TSH secretion and enhance PRL, GH and ACTH. It is believed that opioids elicit their action at the hypothalamic level, most likely by modulating the liberation of hypothalamic releasing or inhibiting factors. In healthy male adults the endogenous opioid peptides (EOP) produce a decrease in serum levels of gonadotropins. Administration of specific opiate antagonists decreases luteinizing hormone (LH) release and increases the frequency and amplitude of the LH pulses. The effects of EOP and specific opiate antagonists are altered in some hypothalamic-hypophysis-testis axis pathologies.
3-Endogenous opioids and hypogonadism in human obesity.
Blank DM, Clark RV, Heymsfield SB, Rudman DR, Blank MS.
Yerkes Regional Primate Research Center, Emory University, Atlanta, GA 30322.
Massively obese males often show symptoms of hypogonadism, but the mechanism for this is unclear. Increased endogenous opioid inhibition of the hypothalamic GnRH pulse generator resulting in insufficient stimulation of the pituitary gonadotroph has been proposed as a possible mechanism. If this hypothesis is correct, obese males should be more sensitive to the LH-elevating effects of the opiate antagonist, naloxone, than men of normal weight and gonadal status. This study investigated the etiology of obesity-related hypogonadism by examining luteinizing hormone (LH) and follicle stimulating hormone (FSH) responses to gonadotropin-releasing hormone (GnRH) and to infusions of saline or naloxone. Subjects were five obese (201 +/- 14% IBW) and five normal weight (control) (97 +/- 4% IBW) males. Before treatment, obese males had significantly (p < 0.05) lower testosterone levels than control subjects (307 +/- 72 vs. 597 +/- 49 ng/dl), whereas estradiol, androstenedione, and dehydroepiandrosterone levels were not different between the two groups. Both groups showed equivalent elevations in LH (fourfold to sixfold) in response to GnRH stimulation, but obese patients had significantly lower basal (p < 0.05) and GnRH-stimulated (p < 0.01) FSH levels. Infusions of naloxone (but not saline) led to significant (p < 0.01) increases in LH above preinfusion baseline levels (20.5 +/- 2.8% in obese and 28.6 +/- 6.3% in controls). In control subjects, integrated LH levels during naloxone infusion were not significantly elevated above those found during saline infusion, while obese subjects exhibited a 43% augmentation of integrated LH (31.0 +/- 5.3 ng/ml during naloxone vs. 21.7 +/- 1.8 ng/ml during saline, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
4-The effect of nalmefene on pulsatile secretion of luteinizing hormone and prolactin in men.
Graves GR, Kennedy TG, Weick RF, Casper RF.
Division of Reproductive Sciences, University of Toronto, Ontario, Canada.
Luteinizing hormone (LH) and prolactin are released in pulses which are relatively synchronous in the luteal phase of the menstrual cycle in women. The concordance of LH and prolactin pulses in normal men has not been reported. The objectives of this study were firstly to determine whether LH and prolactin pulses are synchronous in men, and secondly to examine the effects of naloxone and a new orally active opiate antagonist, nalmefene, on LH and prolactin release in men. Three groups of normal male subjects received saline infusion (control n = 5), naloxone infusion (2 mg/h; n = 5) or nalmefene (10 mg p.o.; n = 6). Blood samples were collected every 15 min for 2 h before and 6 h after study medication for determination of LH, prolactin and testosterone by radioimmunoassay. Both naloxone and nalmefene resulted in a significant increase in LH pulse frequency and in mean serum LH and testosterone concentrations with no change in LH pulse amplitude, prolactin pulse frequency or amplitude. In controls, 61% of LH pulses were synchronous with prolactin pulses. There was a decrease in concomitance of LH and prolactin pulses with naloxone (48%) and nalmefene (24%; P < 0.025) administration. In contrast, 52% of prolactin pulses were concomitant with LH pulses in controls, while naloxone (100%) but not nalmefene (67%) resulted in a significant (P < 0.01) increase in pulse synchrony. The difference observed between naloxone and nalmefene on prolactin--LH pulse synchrony is probably due to differential opioid receptor activity at the pituitary and hypothalamic level.(ABSTRACT TRUNCATED AT 250 WORDS)
5-Different effects of aging on the opioid mechanisms controlling gonadotropin and cortisol secretion in man.
Coiro V, Passeri M, Volpi R, Marchesi M, Bertoni P, Fagnoni F, Schianchi L, Bianconi L, Marcato A, Chiodera P.
Cattedra di Clinica Medica, Universita di Parma, Italia.
The present study was undertaken in order to assess the influence of aging on the endogenous opioid control of gonadotropin and adrenocorticotropin/cortisol secretion in man. For this purpose, the capability of the opioid antagonist naloxone to increase circulating levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and cortisol was tested in male subjects of different ages. Thirty normal men were randomly chosen and divided into 3 groups by age: group I = 22-40 years (n = 10); group II = 41-59 years (n = 10); group III = 62-80 years (n = 10). Since the men of group III showed higher basal serum gonadotropin concentrations than the subjects of group I and group II, we selected from a large population a fourth group of elderly men with normal basal LH and FSH levels: group IV = 61-82 years (n = 7). All subjects were tested for 120 min during the intravenous administration of naloxone (4 mg given in an intravenous bolus at time 0, plus 10 mg infused for 2 h). Control tests with normal saline instead of naloxone were performed in all groups. All subjects had similar blood testosterone and cortisol levels, whereas LH and FSH concentrations were significantly higher in group III than in groups I, II and IV. Naloxone increased plasma cortisol concentrations by 50% in all groups. The cortisol secretory response followed a similar pattern regardless of age.(
6-Endorphins in male impotence: evidence for naltrexone stimulation of erectile activity in patient therapy.
Fabbri A, Jannini EA, Gnessi L, Moretti C, Ulisse S, Franzese A, Lazzari R, Fraioli F, Frajese G, Isidori A.
Institute of V Clinica Medica, University of Rome La Sapienza, Italy.
In the present study we evaluated whether naltrexone administration could stimulate sexual function in 30 male patients, ages 25 to 50 years, with idiopathic impotence of at least one year's duration and not of organic etiology. The patients received naltrexone (50 mg/day) or placebo, on a random basis for two weeks. Sexual performance, expressed as the number of full coitus/week, was assessed before (time 0) and during (on days 7 and 15) each treatment. The naltrexone therapy significantly increased the number of successful coitus compared to placebo after 7 and 15 days of treatment: improvement of sexual performance was evident in 11 out of the 15 treated patients. All the patients experienced a significant increase in morning and spontaneous full penile erections/week. No significant side effects were reported. Endocrine studies revealed no significant modification of plasma LH, FSH or testosterone by naltrexone, suggesting that the positive effect of the drug on sexual behavior was exerted at a central level. A two-month follow-up, at which time patients were off treatment, erectile capacity had returned to baseline in 10 patients, while five reported complete recovery of their sexual ability. We hypothesize that an alteration in central opioid tone is present in idiopathic impotence and is involved in the impairment of sexual behavior.
Opioid antagonists and HPTA function
I just heard about the possible effect of opioid antagonists in LH secretion in another board and went to pub med looking for studies on this hoping I could generate some discussion here.
This is the post that started this:
"Now for the most important piece of the post cycle recovery puzzle that you never hear bodybuilders talk about because they usually have no idea. The opioidergic regulation of testosterone. Without going to great lengths in explaining opioids and their effects on hormones and the brain, natural opiates are released in response to the increase in LH by the use of estrogen inhibitors. So you've got increased LH and increased natural opiate levels. Now when the estrogen inhibitors are taken away the LH is greatly reduced and you're back to square one. So your natural opiate levels are still high. LH will not be stimulated until it comes back down. That is in a sense why HCG and estrogen inhibitors are only so affective at stimulating testicular function and restoring the HPT axis. So since opiates suppress gonadotropin secretion i.e. testosterone secretion using opiate antagonists can help bodybuilders completely recover. REVIA is the most popular. Read all you can on the subject because it really is the missing link of post cycle recovery. Later!"
He doesn't provide any references so I went to check it out and did found some stuff (see below). I didn't find anything about the increase in endogenous opioids from LH increases, but I haven't searched yet (anyone knows anything about this?).
Study number found a significant impact on LH levels after naxolone treatment (in goats....).
Second one has this bit that intrigues me:
"Administration of specific opiate antagonists decreases luteinizing hormone (LH) release and increases the frequency and amplitude of the LH pulses"
If I'm not mistaken number 3 shows that naloxone is effective in stimulating LH relese in obese patients, nut not in normal individuals.
Number 4 shows a positive effect in LH and testosterone levels from two different antagonists and some stuff about LH and prolactin pulse sinchrony that is probably meaningless for our purposes.
Number 5 shows a 50% increase in cortisol. Not so good.
Number 6 shows a positive impact in sexual function even without any noticeable changes in hormone levels.
I am not sure this is actually worth trying during post cycle therapy (pct), but I'd love to hear people's opinions on this. These drugs have some unpleasant side effects but I think I'm willing to give it a try if I'm convinced there may be something to it.
Thoughts please?
1-Effect of naloxone on the plasma levels of LH, FSH, prolactin and testosterone in Beetal bucks.
Singh B, Dixit VD, Singh P, Georgie GC, Dixit VP.
Department of Animal Production Physiology, CCS Haryana Agricultural University, 125004, Hisar, India
Ten adult male Beetal goats were used for the study to elucidate the modulation of gonadotrophin, prolactin and testosterone secretion by endogenous opioid peptides. An indwelling catheter was placed in the jugular vein of each buck 20h before the onset of the experiment. Bucks were divided randomly into two groups: Group I (n=5) received naloxone at a dose rate of 1mg/kg body weight (BW) and Group II (n=5) received naloxone at a dose rate of 2mg/kg BW intravenous. Blood samplings were done from 2h before treatment until 2h after treatment at 15min intervals. Blood samples were quantified for plasma LH, FSH and prolactin concentration using a heterologous double antibody radioimmunoassay (RIA) and testosterone concentration was quantified by coat-a-count RIA kit. The mean plasma LH levels during pretreatment phase were 0.41+/-0.03ng/ml in Group I and 0.44+/-0.02ng/ml in Group II which significantly (p<0.05) increased to 0.91+/-0.05ng/ml in Group I and 1.53+/-0.07ng/ml in Group II. The mean plasma FSH levels did not show a difference in pre- and post-treatment animals in both groups. A significant (p<0.05) increase in plasma testosterone concentration was observed in both groups after naloxone treatment, whereas, a decrease (p<0.05) was observed in plasma prolactin levels after naloxone treatment. Thus, it can be concluded that endogenous opioids do play an important role in modulating plasma LH, prolactin and testosterone concentrations in male goats.
2-[Interaction of endogenous opioid peptides with the function of the hypothalamo-hypophyseal-testicular axis]
[Article in Spanish]
Pedron Nuevo N.
Unidad de Investigacion Medica en Biologia de la Reproduccion. Division de Investigacion Biomedica. IMSS, Mexico, D.F.
Since the discovery of endogenous opioid peptides and opioid receptors in the brain, their has been considerable interest in their possible role in a variety of physiological and pharmacological processes. The endogenous opioids and opiate active substances have been clearly implicated in the regulation of male reproductive function. It has been demonstrated that opioid peptides inhibit gonadotropin and TSH secretion and enhance PRL, GH and ACTH. It is believed that opioids elicit their action at the hypothalamic level, most likely by modulating the liberation of hypothalamic releasing or inhibiting factors. In healthy male adults the endogenous opioid peptides (EOP) produce a decrease in serum levels of gonadotropins. Administration of specific opiate antagonists decreases luteinizing hormone (LH) release and increases the frequency and amplitude of the LH pulses. The effects of EOP and specific opiate antagonists are altered in some hypothalamic-hypophysis-testis axis pathologies.
3-Endogenous opioids and hypogonadism in human obesity.
Blank DM, Clark RV, Heymsfield SB, Rudman DR, Blank MS.
Yerkes Regional Primate Research Center, Emory University, Atlanta, GA 30322.
Massively obese males often show symptoms of hypogonadism, but the mechanism for this is unclear. Increased endogenous opioid inhibition of the hypothalamic GnRH pulse generator resulting in insufficient stimulation of the pituitary gonadotroph has been proposed as a possible mechanism. If this hypothesis is correct, obese males should be more sensitive to the LH-elevating effects of the opiate antagonist, naloxone, than men of normal weight and gonadal status. This study investigated the etiology of obesity-related hypogonadism by examining luteinizing hormone (LH) and follicle stimulating hormone (FSH) responses to gonadotropin-releasing hormone (GnRH) and to infusions of saline or naloxone. Subjects were five obese (201 +/- 14% IBW) and five normal weight (control) (97 +/- 4% IBW) males. Before treatment, obese males had significantly (p < 0.05) lower testosterone levels than control subjects (307 +/- 72 vs. 597 +/- 49 ng/dl), whereas estradiol, androstenedione, and dehydroepiandrosterone levels were not different between the two groups. Both groups showed equivalent elevations in LH (fourfold to sixfold) in response to GnRH stimulation, but obese patients had significantly lower basal (p < 0.05) and GnRH-stimulated (p < 0.01) FSH levels. Infusions of naloxone (but not saline) led to significant (p < 0.01) increases in LH above preinfusion baseline levels (20.5 +/- 2.8% in obese and 28.6 +/- 6.3% in controls). In control subjects, integrated LH levels during naloxone infusion were not significantly elevated above those found during saline infusion, while obese subjects exhibited a 43% augmentation of integrated LH (31.0 +/- 5.3 ng/ml during naloxone vs. 21.7 +/- 1.8 ng/ml during saline, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
4-The effect of nalmefene on pulsatile secretion of luteinizing hormone and prolactin in men.
Graves GR, Kennedy TG, Weick RF, Casper RF.
Division of Reproductive Sciences, University of Toronto, Ontario, Canada.
Luteinizing hormone (LH) and prolactin are released in pulses which are relatively synchronous in the luteal phase of the menstrual cycle in women. The concordance of LH and prolactin pulses in normal men has not been reported. The objectives of this study were firstly to determine whether LH and prolactin pulses are synchronous in men, and secondly to examine the effects of naloxone and a new orally active opiate antagonist, nalmefene, on LH and prolactin release in men. Three groups of normal male subjects received saline infusion (control n = 5), naloxone infusion (2 mg/h; n = 5) or nalmefene (10 mg p.o.; n = 6). Blood samples were collected every 15 min for 2 h before and 6 h after study medication for determination of LH, prolactin and testosterone by radioimmunoassay. Both naloxone and nalmefene resulted in a significant increase in LH pulse frequency and in mean serum LH and testosterone concentrations with no change in LH pulse amplitude, prolactin pulse frequency or amplitude. In controls, 61% of LH pulses were synchronous with prolactin pulses. There was a decrease in concomitance of LH and prolactin pulses with naloxone (48%) and nalmefene (24%; P < 0.025) administration. In contrast, 52% of prolactin pulses were concomitant with LH pulses in controls, while naloxone (100%) but not nalmefene (67%) resulted in a significant (P < 0.01) increase in pulse synchrony. The difference observed between naloxone and nalmefene on prolactin--LH pulse synchrony is probably due to differential opioid receptor activity at the pituitary and hypothalamic level.(ABSTRACT TRUNCATED AT 250 WORDS)
5-Different effects of aging on the opioid mechanisms controlling gonadotropin and cortisol secretion in man.
Coiro V, Passeri M, Volpi R, Marchesi M, Bertoni P, Fagnoni F, Schianchi L, Bianconi L, Marcato A, Chiodera P.
Cattedra di Clinica Medica, Universita di Parma, Italia.
The present study was undertaken in order to assess the influence of aging on the endogenous opioid control of gonadotropin and adrenocorticotropin/cortisol secretion in man. For this purpose, the capability of the opioid antagonist naloxone to increase circulating levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and cortisol was tested in male subjects of different ages. Thirty normal men were randomly chosen and divided into 3 groups by age: group I = 22-40 years (n = 10); group II = 41-59 years (n = 10); group III = 62-80 years (n = 10). Since the men of group III showed higher basal serum gonadotropin concentrations than the subjects of group I and group II, we selected from a large population a fourth group of elderly men with normal basal LH and FSH levels: group IV = 61-82 years (n = 7). All subjects were tested for 120 min during the intravenous administration of naloxone (4 mg given in an intravenous bolus at time 0, plus 10 mg infused for 2 h). Control tests with normal saline instead of naloxone were performed in all groups. All subjects had similar blood testosterone and cortisol levels, whereas LH and FSH concentrations were significantly higher in group III than in groups I, II and IV. Naloxone increased plasma cortisol concentrations by 50% in all groups. The cortisol secretory response followed a similar pattern regardless of age.(
6-Endorphins in male impotence: evidence for naltrexone stimulation of erectile activity in patient therapy.
Fabbri A, Jannini EA, Gnessi L, Moretti C, Ulisse S, Franzese A, Lazzari R, Fraioli F, Frajese G, Isidori A.
Institute of V Clinica Medica, University of Rome La Sapienza, Italy.
In the present study we evaluated whether naltrexone administration could stimulate sexual function in 30 male patients, ages 25 to 50 years, with idiopathic impotence of at least one year's duration and not of organic etiology. The patients received naltrexone (50 mg/day) or placebo, on a random basis for two weeks. Sexual performance, expressed as the number of full coitus/week, was assessed before (time 0) and during (on days 7 and 15) each treatment. The naltrexone therapy significantly increased the number of successful coitus compared to placebo after 7 and 15 days of treatment: improvement of sexual performance was evident in 11 out of the 15 treated patients. All the patients experienced a significant increase in morning and spontaneous full penile erections/week. No significant side effects were reported. Endocrine studies revealed no significant modification of plasma LH, FSH or testosterone by naltrexone, suggesting that the positive effect of the drug on sexual behavior was exerted at a central level. A two-month follow-up, at which time patients were off treatment, erectile capacity had returned to baseline in 10 patients, while five reported complete recovery of their sexual ability. We hypothesize that an alteration in central opioid tone is present in idiopathic impotence and is involved in the impairment of sexual behavior.
