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NEW ORLEANS – according to an interim analysis of a postapproval clinical trial.
Testosterone nasal gel is a shorter-acting formulation of testosterone that “can mimic normal physiology,” said John Masterson, MD, a urology resident at the University of Miami. The 4.5% formulation, which was approved by the Food and Drug Administration in 2014 and is marketed as Natesto, delivers 11 mg of testosterone per dose and is dosed three times daily for testosterone replacement therapy.
The negative feedback exerted by other exogenous testosterone formulations on the hypothalamic-pituitary-gonadal (HPG) axis is known to inhibit spermatogenesis, Dr. Masterson said in a video interview at the annual meeting of the Endocrine Society.
Dr. Masterson, senior author Ranjith Ramasamy, MD, and their colleagues hypothesized that the shorter duration of action of testosterone in the nasal gel formulation would result in some conservation of gonadotropin-releasing hormone (GnRH) pulsatility, less inhibition of the HPG axis, and preservation of spermatogenesis.
In the same interview, Dr. Ramasamy, director of reproductive urology at the University of Miami, noted that “the levels of testosterone in men rise about an hour or 2 after administration [of the gel] and seem to drop off about 2 to 4 hours after the peak.” That is closer to normal physiology than other delivery systems in which “the levels of testosterone are pretty high during the day and therefore could lead to some of the side effects that we see with testosterone.”
The phase 4 prospective study enrolled 56 men aged between 18 and 55 years who had low levels of testosterone (baseline mean, 233.97 ng/dL). The mean age was 37 years.
“There are mostly younger men in our study ... and they’re usually coming in with one or two hypogonadal complaints – lack of energy, fatigue, some with erectile dysfunction,” Dr. Masterson explained in the interview. Improvement was seen in those realms, but the differences didn’t reach statistical significance, because baseline quality of life was already fairly high for these otherwise healthy men. “What we can say is that on the drug, quality of life certainly did not get worse,” he said.
At baseline, the mean luteinizing hormone (LH) level was 3.66 IU/mL, and the mean follicle stimulating hormone (FSH) level was 4.01 IU/mL.
Men were eligible to participate if they had two morning blood samples with age-adjusted low testosterone levels, and a total motile sperm count more than 5 million/ejaculation. Participants received 11-mg nasal testosterone gel three times daily for 6 months.
By 1 month into the study, 43 patients had a median testosterone level of 573 ng/dL. Fifteen patients have thus far completed all 6 months of the study and they had a median testosterone level of 604 ng/dL.
At baseline, sperm concentration was a mean 21.32 million/mL with 50% motility, and a total sperm count of 32.23 million/ejaculation. Sperm concentration at 6 months was unchanged at a median 21 million/mL.
Motility was preserved at a median 51.5% after 6 months of therapy, a statistically insignificant difference from 54% motility at baseline. Total motile sperm count decreased from a median 29.3 million/ejaculation at baseline to 19.5 million/ejaculation, a difference that didn’t reach statistical significance.
“What that means is that this nasal testosterone gel [could] be used in men who have low testosterone and are interested in preserving fertility,” said Dr. Masterson.
Dr. Ramasamy said that they’re seeing early confirmation of their initial hypothesis about the nasal gel formulation in this interim analysis. “Because it’s short acting, we believe some of the GnRH pulses and the LH and FSH that are released by the pituitary gland are still maintained, compared with the other forms of testosterone therapy, which can cause complete suppression of the [HPG] axis.”
In discussion with attendees at the poster session at which the research was featured, Dr. Masterson explained that quality-of-life measures were also collected as part of the study and will be presented separately. In addition to information about erectile function, men were asked about libido – a more complex phenomenon than erectile function alone – and early analysis showed a robust response, he said.
He acknowledged that it is not known whether craniofacial circulation facilitates testosterone transport to the brain when the nasal gel testosterone formulation is used, but that it is mechanistically plausible.
Dr. Masterson added that, practically speaking, patients should be aware that the formulation is a gel. “It sort of has to be painted on” the nasal septum within the nostrils, he said.
Aytu BioScience, which markets Natesto, partially supported the study. Dr Masterson reported no disclosures or conflicts of interest.
NEW ORLEANS – according to an interim analysis of a postapproval clinical trial.
Testosterone nasal gel is a shorter-acting formulation of testosterone that “can mimic normal physiology,” said John Masterson, MD, a urology resident at the University of Miami. The 4.5% formulation, which was approved by the Food and Drug Administration in 2014 and is marketed as Natesto, delivers 11 mg of testosterone per dose and is dosed three times daily for testosterone replacement therapy.
The negative feedback exerted by other exogenous testosterone formulations on the hypothalamic-pituitary-gonadal (HPG) axis is known to inhibit spermatogenesis, Dr. Masterson said in a video interview at the annual meeting of the Endocrine Society.
Dr. Masterson, senior author Ranjith Ramasamy, MD, and their colleagues hypothesized that the shorter duration of action of testosterone in the nasal gel formulation would result in some conservation of gonadotropin-releasing hormone (GnRH) pulsatility, less inhibition of the HPG axis, and preservation of spermatogenesis.
In the same interview, Dr. Ramasamy, director of reproductive urology at the University of Miami, noted that “the levels of testosterone in men rise about an hour or 2 after administration [of the gel] and seem to drop off about 2 to 4 hours after the peak.” That is closer to normal physiology than other delivery systems in which “the levels of testosterone are pretty high during the day and therefore could lead to some of the side effects that we see with testosterone.”
The phase 4 prospective study enrolled 56 men aged between 18 and 55 years who had low levels of testosterone (baseline mean, 233.97 ng/dL). The mean age was 37 years.
“There are mostly younger men in our study ... and they’re usually coming in with one or two hypogonadal complaints – lack of energy, fatigue, some with erectile dysfunction,” Dr. Masterson explained in the interview. Improvement was seen in those realms, but the differences didn’t reach statistical significance, because baseline quality of life was already fairly high for these otherwise healthy men. “What we can say is that on the drug, quality of life certainly did not get worse,” he said.
At baseline, the mean luteinizing hormone (LH) level was 3.66 IU/mL, and the mean follicle stimulating hormone (FSH) level was 4.01 IU/mL.
Men were eligible to participate if they had two morning blood samples with age-adjusted low testosterone levels, and a total motile sperm count more than 5 million/ejaculation. Participants received 11-mg nasal testosterone gel three times daily for 6 months.
By 1 month into the study, 43 patients had a median testosterone level of 573 ng/dL. Fifteen patients have thus far completed all 6 months of the study and they had a median testosterone level of 604 ng/dL.
At baseline, sperm concentration was a mean 21.32 million/mL with 50% motility, and a total sperm count of 32.23 million/ejaculation. Sperm concentration at 6 months was unchanged at a median 21 million/mL.
Motility was preserved at a median 51.5% after 6 months of therapy, a statistically insignificant difference from 54% motility at baseline. Total motile sperm count decreased from a median 29.3 million/ejaculation at baseline to 19.5 million/ejaculation, a difference that didn’t reach statistical significance.
“What that means is that this nasal testosterone gel [could] be used in men who have low testosterone and are interested in preserving fertility,” said Dr. Masterson.
Dr. Ramasamy said that they’re seeing early confirmation of their initial hypothesis about the nasal gel formulation in this interim analysis. “Because it’s short acting, we believe some of the GnRH pulses and the LH and FSH that are released by the pituitary gland are still maintained, compared with the other forms of testosterone therapy, which can cause complete suppression of the [HPG] axis.”
In discussion with attendees at the poster session at which the research was featured, Dr. Masterson explained that quality-of-life measures were also collected as part of the study and will be presented separately. In addition to information about erectile function, men were asked about libido – a more complex phenomenon than erectile function alone – and early analysis showed a robust response, he said.
He acknowledged that it is not known whether craniofacial circulation facilitates testosterone transport to the brain when the nasal gel testosterone formulation is used, but that it is mechanistically plausible.
Dr. Masterson added that, practically speaking, patients should be aware that the formulation is a gel. “It sort of has to be painted on” the nasal septum within the nostrils, he said.
Aytu BioScience, which markets Natesto, partially supported the study. Dr Masterson reported no disclosures or conflicts of interest.
NEW ORLEANS – according to an interim analysis of a postapproval clinical trial.
Testosterone nasal gel is a shorter-acting formulation of testosterone that “can mimic normal physiology,” said John Masterson, MD, a urology resident at the University of Miami. The 4.5% formulation, which was approved by the Food and Drug Administration in 2014 and is marketed as Natesto, delivers 11 mg of testosterone per dose and is dosed three times daily for testosterone replacement therapy.
The negative feedback exerted by other exogenous testosterone formulations on the hypothalamic-pituitary-gonadal (HPG) axis is known to inhibit spermatogenesis, Dr. Masterson said in a video interview at the annual meeting of the Endocrine Society.
Dr. Masterson, senior author Ranjith Ramasamy, MD, and their colleagues hypothesized that the shorter duration of action of testosterone in the nasal gel formulation would result in some conservation of gonadotropin-releasing hormone (GnRH) pulsatility, less inhibition of the HPG axis, and preservation of spermatogenesis.
In the same interview, Dr. Ramasamy, director of reproductive urology at the University of Miami, noted that “the levels of testosterone in men rise about an hour or 2 after administration [of the gel] and seem to drop off about 2 to 4 hours after the peak.” That is closer to normal physiology than other delivery systems in which “the levels of testosterone are pretty high during the day and therefore could lead to some of the side effects that we see with testosterone.”
The phase 4 prospective study enrolled 56 men aged between 18 and 55 years who had low levels of testosterone (baseline mean, 233.97 ng/dL). The mean age was 37 years.
“There are mostly younger men in our study ... and they’re usually coming in with one or two hypogonadal complaints – lack of energy, fatigue, some with erectile dysfunction,” Dr. Masterson explained in the interview. Improvement was seen in those realms, but the differences didn’t reach statistical significance, because baseline quality of life was already fairly high for these otherwise healthy men. “What we can say is that on the drug, quality of life certainly did not get worse,” he said.
At baseline, the mean luteinizing hormone (LH) level was 3.66 IU/mL, and the mean follicle stimulating hormone (FSH) level was 4.01 IU/mL.
Men were eligible to participate if they had two morning blood samples with age-adjusted low testosterone levels, and a total motile sperm count more than 5 million/ejaculation. Participants received 11-mg nasal testosterone gel three times daily for 6 months.
By 1 month into the study, 43 patients had a median testosterone level of 573 ng/dL. Fifteen patients have thus far completed all 6 months of the study and they had a median testosterone level of 604 ng/dL.
At baseline, sperm concentration was a mean 21.32 million/mL with 50% motility, and a total sperm count of 32.23 million/ejaculation. Sperm concentration at 6 months was unchanged at a median 21 million/mL.
Motility was preserved at a median 51.5% after 6 months of therapy, a statistically insignificant difference from 54% motility at baseline. Total motile sperm count decreased from a median 29.3 million/ejaculation at baseline to 19.5 million/ejaculation, a difference that didn’t reach statistical significance.
“What that means is that this nasal testosterone gel [could] be used in men who have low testosterone and are interested in preserving fertility,” said Dr. Masterson.
Dr. Ramasamy said that they’re seeing early confirmation of their initial hypothesis about the nasal gel formulation in this interim analysis. “Because it’s short acting, we believe some of the GnRH pulses and the LH and FSH that are released by the pituitary gland are still maintained, compared with the other forms of testosterone therapy, which can cause complete suppression of the [HPG] axis.”
In discussion with attendees at the poster session at which the research was featured, Dr. Masterson explained that quality-of-life measures were also collected as part of the study and will be presented separately. In addition to information about erectile function, men were asked about libido – a more complex phenomenon than erectile function alone – and early analysis showed a robust response, he said.
He acknowledged that it is not known whether craniofacial circulation facilitates testosterone transport to the brain when the nasal gel testosterone formulation is used, but that it is mechanistically plausible.
Dr. Masterson added that, practically speaking, patients should be aware that the formulation is a gel. “It sort of has to be painted on” the nasal septum within the nostrils, he said.
Aytu BioScience, which markets Natesto, partially supported the study. Dr Masterson reported no disclosures or conflicts of interest.
REPORTING FROM ENDO 2019
