Peptide Studies (A)

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Peptide Studies (A)

Whilst there was significant research into these peptides in a broader sense, there was very little research into their role in the niche areas identified, sexual function being the exception. What little research is available, often did not meet the requirement of being the consequence of a study in the niche area. Where an article was identified but did not meet the required criteria, but had some relevance to the niche area, we have included the full citation for completeness.



  • The majority of the clinical research into AOD-9604 is in relation to the role it plays in fat metabolism, which, while showing promising results in the animal testing phase, has shown underwhelming results in human testing.
  • A search of the Clinical Trials database provided no trials relating to AOD-9604 and no research relating to its role in improved skin or collagen production.
  • A review of the research involving C-terminal growth fragment Tyr-hGH177-191 (AOD-9604) was undertaken, yielding no additional results.
  • A review of all research involving C-terminal growth fragments was undertaken, as often research refers to broader categories. All available research in this area was reviewed. No studies involving AOD-9604 and its effect of skin could be located.

Other Research into AOD-9604

  • AOD-9604 was referenced in a patent application, which provides some limited details of its role in collagen production as it is relevant to osteoarthritis.
  • This patent application provides a good summary of the role of Tyr-hGH177-191.

Rapamycin Cream

  • Rapamycin is best known as an oral immunosuppressant, used primarily in kidney transplant patients. Research in 2019 confirmed, in a topical form, rapamycin is effective in reducing the signs of aging in skin. It is also effective in the treatment of facial angiofibroma, improving skin quality.
  • Chung CL, Lawrence I, Hoffman M, Elgindi D, Nadhan K, Potnis M, Jin A, Sershon C, Binnebose R, Lorenzini A, Sell C. Topical rapamycin reduces markers of senescence and aging in human skin: an exploratory, prospective, randomized trial. Geroscience. 2019; 41:861–69.
    • This is the leading research in this area.
    • This placebo-controlled study tested the hypothesis " rapamycin treatment can ameliorate age-related disorder and dysfunction in human tissue through a reduction in senescence."
    Study Design
    • Participants received two identical unmarked containers, one containing rapamycin and one a placebo, with instructions to apply the contents to either the left or right hand at 24-48 hour intervals. After initiating the topical application, participants were followed up at 2, 4, 6, and 8 months. The skin was photographed at each follow-up appointment, a blood test taken at six months, and a punch biopsy taken from each hand at the final visit.
    • Thirty-six participants were enrolled in the study, with 19 lost to follow-up or discontinued. It was a requirement that all participants were over 40 years of age, with no medical history of diabetes or hypercholesterolemia. Of the remaining 17 participants, 13 agreed to the bloods and biopsies.
    • Immunohistology revealed a statistically significant reduction in the expression of the protein p16I NK4A in the epidermal layer of the skin in the rapamycin-treated samples. While a reduction in proteins p21 Cip2 and tp53 was also observed in the rapamycin-treated samples, it did not reach the level of statistical significance.
    • Histology in the rapamycin-treated samples showed a consistent reduction in solar elastosis, with increased organization of the basal layer. The placebo-treated samples showed increased cytokeratin 5/6 staining, however, the small sample size made this difficult to quantify.
    • mRNA analysis showed increased collagen VII in the rapamycin-treated skin samples, with the accompanying reduction in the mRNA level of collagen IV, suggesting elevated protein levels induce feedback regulation.
    • Clinical evaluation of the photographs revealed decreased fine wrinkles, increased dermal volume, brighter and more even skin tone, reduced sagging, and decreased prominence of veins in the rapamycin-treated samples from four months.
    • When previous research was also taken into account, the conclusion was rapamycin reduces entry into senescence, although, researchers could not rule out the possibility that rapamycin was playing a role in the clearance of senescent cells. Regardless, the decreased burden of the senescent cells has improved functionality.
    • The research also suggested rapamycin reduces the inflammatory cytokines in the skin, although further research in this area is required.
    • Improvement in skin quality, shown by increased collagen VII in the basal membrane, was a result of the rapamycin treatment.
  • Chung et al.'s 2019 article discusses the past research into rapamycin cream relative to normal skin, noting that animal studies are ongoing, and short-term studies have largely addressed the safety and tolerability of rapamycin cream. The exception was a small feasibility study in which looked at the potential impact of rapamycin on the aging process in human tissue. When this feasibility study was reviewed it related to oral rapamycin in coronary patients. This suggests the above research is the only study that directly looks at Rapamycin and its role in skin improvement in normal skin.
  • Wang R, Yu Z, Sunchu B, Shoaf J, Dang I, Zhao S, Caples K, Bradley L, Beaver LM, Ho E, Löhr CV, Perez VI. Rapamycin inhibits the secretory phenotype of senescent cells by a Nrf2-independent mechanism. Aging Cell. 2017; 16:564–74.
  • Study Aim
    • This research was not specifically related to skin or collagen, it investigates aging and senescent cells. Senescent cells play a role in the skins aging and appearance.
    Study Design
    • The study used "two models of cellular senescence, stressinduced premature senescence (SIPS) in mouse embryonic fibroblasts (MEFs), and replicative senescence in human WI38 cells." The results were then corroborated in vivo using the Nrf2KO mouse.
    • Markers, such as p16 and p21 gene expression, increased senescenceassociated βgalactosidase staining (βgal), and the presence of secretory inflammatory cytokines and other factors known as SASP were used to evaluate the effect of rapamycin. These markers are reliable indicators of senescence.
    • Preincubation with rapamycin for 24 hours reduced senescence markers dependent on Nrf2, such as p16 and p21. This correlated to an inhibition of DNA damage indicated by pH2X marker.
    • In the Nrf2KO mouse, a decrease in βgal staining and proinflammatory cytokines in serum and fat tissue was observed following rapamycin.
    • The primary finding relevant to rapamycin's role in skin is the "suppression of the SASP by rapamycin, but without the actual removal of senescent cells may have broader beneficial effects as a therapy against agerelated diseases."
    • In relation to rapamycin's role in senescence, the research found, "cell senescence is a complex process that involves at least two arms, and rapamycin uses Nrf2 to regulate cell cycle arrest, but not the production of SASP."
    • It is important to note this was not a topical application of rapamycin.
  • Viswanath V , Thakur P, Pund P. Use of topical rapamycin in facial angiofibromas in Indian skin type , Indian Journal of Dermatology. 2016; 61(1):119
  • Study Aims
    • The study aimed to evaluate the efficacy of rapamycin in the treatment of facial angiofibroma in Indian patients.
    Study Design
    • Five patients attending dermatology outpatient appointments between May and December 2014 were included in this study. Four had facial angiofibromas and cutaneous features of tuberous sclerosis, and one had no features of tuberous sclerosis, but facial angiofibroma confirmed histopathologically.
    • Rapamycin was applied topically in varying doses and intervals, A cross-sectional analysis was completed in December 2014, noting the duration of the rapamycin application, and its effects. All participants continued to apply the topical rapamycin and follow-up was ongoing.
    • Patients showed improved erythema within two weeks of starting treatment. All participants showed rapid improvement, with the speed of improvement being dose-dependent. The improvement was faster in children, when compared to adults.
    • Rapamycin is an effective treatment in the treatment of angiofibroma, improving markedly the condition of the skin.
  • Balestri R, Neri I, Patrizi A, Angileri L, Ricci L, Magnano M. Analysis of current data on the use of topical rapamycin in the treatment of facial angiofibromas in tuberous sclerosis complex. J Eur Acad Dermatol Venereol. 2015;29(1):14-20.
    • This is not strictly a clinical study. Rather, the research looks to review available data and draw conclusions based on the results.
    Study Aim
    • The study aimed to review the current data on the use of rapamycin in facial angiofibroma in patients with tuberous sclerosis.
    Study Design
    • This was a retrospective review of the literature considering 16 reports into the use of rapamycin cream, in 84 patients with facial angiofibroma.
    • Rapamycin was applied topically in varying doses and intervals, A cross-sectional analysis was completed in December 2014, noting the duration of the rapamycin application, and its effects. All participants continued to apply the topical rapamycin and follow-up was ongoing.
    • 94% of patients showed improvements in the condition of their skin if treatment with rapamycin was started early enough. A range of different concentrations of rapamycin cream (0.003%-1%) were used. Only four adverse events were recorded.
    • Rapamycin cream is effective in the treatment of facial angiofibroma, improving the skin quality.
  • T he commercial and trade names of rapamycin cream, sirolimus ointment and rapamune were also reviewed, but yielded no additional results.

Other Rapamycin Cream Research

  • One clinical trial was located relating to rapamycin, NCT01853423 Clinical Trial Tuberous Sclerosis Complex: Facial Angiofibroma Skin Cream.
  • Study Aim
    • The 2013 study aimed to evaluate the efficacy of a 0.1% rapamune cream in the treatment of facial angiofibroma in tuberous sclerosis patients.
    Study Design
    • The study recruited 11 patients in the first year. A topical 0.1% rapamune cream was given to each participant. It was to be applied twice daily for two weeks, then once daily therein. The patients were reviewed at 0, 1, 3, 6, and 12 months, with photographs taken at each visit.
    • The study concluded in 2016. However, no results are recorded in the Clinical Trials database.
  • Blagosklonny MV. Aging and immortality: quasi-programmed senescence and its pharmacologic inhibition. Cell Cycle. 2006; 5:2087–102. This article was not specifically related to skin or collagen, it discusses aging and senescence cells in a broader sense. It is also just a review, rather than a study.
  • Yang F, Tanaka M, Wataya-Kaneda M, et al. Topical application of rapamycin ointment ameliorates Dermatophagoides farina body extract-induced atopic dermatitis in NC/Nga mice. Exp Dermatol. 2014;23(8):568-572. This article found rapamycin cream decreased the skin inflammation caused by atopic dermatitis improving the appearance of skin. It is included for completeness as it of peripheral relevance to the studies sought. The full article is not available in the public domain.

GHRH Analogs (Sermorelin or CJC-1295)

  • There was no specific research on Sermorelin or CJC-1295 available in the public domain. Given the role of the two GHRH Analogs in the secretion of growth hormone, a review of available research on the role of growth hormone in skin was also undertaken and reviewed for any specific research on Sermorelin and CJC-1295.
  • Póvoa, G.A., & Diniz, L. (2011). Growth hormone system: skin interactions. Anais brasileiros de dermatologia, 86 6, 1159-65.
    • This article was the only research available relating to Sermorelin and CJC-1295 and the role they have in skin. It is included for completeness on the following basis.
    • Sermorelin and CJC-1295 are analogs of the same peptide. They stimulate the release of Growth Hormone by the pituitary gland. Sermorelin specifically stimulates the gene transcription of the pituitary mRNA and activates the anterior pituitary receptors for GHRH resulting to increased growth hormone secretion, which has been shown to improve skin.
  • A search of the Clinical Trials database provided no trials relating to Sermorelin and CJC-1295 found no research relating to its role in improved skin or collagen production.

Other Sermorelin and CJC-1205 Reseach

  • Most of the research in this area is broad and looks at the effect of growth hormone on the skin, rather than the process which stimulated the increase in growth hormone.
  • Bausek, N. CJC-1295 Overview and Comparison to other GHRP & GHRH Peptides. 7 August 2020 (unpublished). Although this article appears on a fitness website, the author holds a PHD in this area. The article provides a good overview of CJC-1295.


GHK-Cu (Topical Foam and Injectable)

  • There is no specific research in the public domain relating to the role of GHK-Cu in the treatment of hair loss. Given this, the search was broadened to biomimetic peptides, of which GHK-Cu is one.
  • The search term tripeptide-copper was employed to good success.
  • Rinaldi, F. Marzani, B. Pinto, D. Sorbellini, E. (2019) Randomized controlled trial on a PRP-like cosmetic, biomimetic peptides based, for the treatment of alopecia areata, Journal of Dermatological Treatment, 201930:6, 588-593
  • Study Aim
    • This study aimed to investigate the efficacy of the cosmetic product, TR-M-PRP, containing biomimetic peptides specific for hair growth, including GHK-Cu.
    • This study has some limited applicability. GHK-Cu is one of the biomimetric peptides in the treatment formulation.
    Study Design
    • The study had 60 participants with alopecia areata. They were aged 18-60. The severity of alopecia tool (SALT) was used to evaluate the alopecia.
    • The efficacy of TR-M-PRP was evaluated by the percentage increase in hair growth and the grading of the overall improvement based on the SALT.
    • Participants were randomized into two groups of 30. One group received the TR-M-PRP treatment, while the other received the placebo.
    • The mean change in SALT score for the treatment group was 18.39, compared to 8.49 for the control group.
    • The percentage regrowth change was 57.07% for the treatment group, compared to 27.96% for the control group at 3 months. These percentages increased to 68.12% and 28.89% respectively, one month after treatment ended.
    • This supports TR-M-PRP's efficacy in the treatment of alopecia areata.
    • A significant improvement was seen by the participants who received the TR-M-PRP treatment. Unfortunately, there is no way of determining the role each biomimetic peptide played in this result.
  • Pyo, Hyun & Yoo, Hyeon & Won, Chong Hyun & Lee, Seung & Kang, Yong & Eun, Hee & Cho, Kwang & Kim, Kyu Han. (2007). The effect of tripeptide-copper complex on human hair growth in vitro. Archives of pharmacal research. 30. 834-9.
  • Study Aim
    • The study aimed to determine the role of tripeptide copper on human hair growth, specifically whether it promotes the growth of human hair follicles.
    Study Design
    • Hair follicles were obtained from the scalps of ten healthy volunteers. The hair follicles were cultured ex vitro, incubated for 12 days, and fed every three days. Tripeptide-copper was added to the final cultures.
    • After 12 days the length of the hair follicles that received the tripeptide-copper were significantly increased, compared to the control group.
    • Results of the MTT assay showed tripeptide-copper had stimulated the elongation of the hair follicles.
    • The growth was dose dependent, with an optimal range established.
    • The study provides evidence that tripeptide-copper stimulates hair growth through the proliferation of DPCs. It also limits their apoptosis.
  • A search of the Clinical Trials database provided no trials relating to GHK-Cu and hair stimulation or loss

Other GHK-Cu Research

  • Pickart, L., & Margolina, A. (2018). Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data. International journal of molecular sciences, 19(7), 1987.
      • The focus of this paper is largely on the qualities of GHK-Cu in skin regeneration. It mentions the effect it has on hair loss. It has been included for completeness.
  • Rose P. T. (2015). Hair restoration surgery: challenges and solutions. Clinical, cosmetic and investigational dermatology, 8, 361–370.
    • This article mentions in passing the use of a liposomal ATP placed into a copper peptide to form a spray for use post-operatively in hair transplant surgery. It has been included for completeness.
  • Pickart, L., Vasquez-Soltero, J. M., & Margolina, A. (2015). GHK Peptide as a Natural Modulator of Multiple Cellular Pathways in Skin Regeneration. BioMed research international, 2015, 648108. .
    • While the focus of this paper is skin regeneration, it mentions the effects on hair follicles, so is included for completeness.
  • A patent application filed in respect of copper peptide and its impact on hair provides some insight into this area.
  • This article discusses copper tripeptide and past research. It illustrates how little research has been done on the role of copper tripeptide in hair growth.


  • A review of research involving C-terminal growth fragment Tyr-hGH177-191 (AOD-9604) was undertaken, yielding no results.
  • A review of all research involving C-terminal growth fragments was undertaken, as often research refers to broader categories. All available research in this area was reviewed. No studies involving AOD-9604 and its effect on hair could be located.
  • A search of the Clinical Trials database provided no trials relating to AOD-0604 and hair stimulation or loss.


PT-141 (Bremelanotide)

  • Rosen RC, Diamond LE, Earle DC, Shadiack AM, Molinoff PB. Double-blind, placebo-controlled evaluation of the safety, pharmacokinetic properties and pharmacodynamic effects of intranasal PT-141, a melanocortin receptor agonist, in healthy males and patients with mild-to-moderate erectile dysfunction. Int J Impot Res 2004; 16: 51–59.
  • Study Aims
    • This study aimed to evaluate the use of PT-141 as a treatment option for erectile dysfunction (ED).
    Study Design
    • There were two phases to this study, phase 1 and phase 2A. The 32 phase 1 participants were healthy males aged 18-45, with no history of ED. The 24 phase 2A participants were healthy males aged 18-65, with a history of ED that had been successfully treated with Viagra.
    • Phase 1 trials involved the internasal administration of PT-141 following an overnight fast and observation post-administration for 12 hours. Phase 2A trials involved the internasal administration of PT-141 one hour after breakfast and observation post-administration for 12 hours. Penile rigidity was measured with a RigiScan.
    • A statistically significant result was seen in the phase 1 group in doses above 7mg, with the extent of the erectile response increasing with an increased dose. The mean duration of base rigidity increased from 41.1 to 126.6 minutes for those receiving PT-141, compared to 5.3 minutes for those receiving placebo.
    • A statistically significant result was seen in the phase 2A group in doses above 7mg, with the extent of the erectile response increasing with an increased dose. The mean duration of base rigidity was 26.0 and 53.8 minutes for those receiving 7mg and 20mg doses, compared to 7.3 minutes for those receiving the placebo.
    • No assessment of libido was made.
  • Rosen RC, Diamond LE, Earle DC, Shadiack AM, Molinoff PB. Evaluation of the safety, pharmacokinetics and pharmacodynamic effects of subcutaneously administered PT-141, a melanocortin receptor agonist, in healthy male subjects and in patients with an inadequate response to Viagra®. Int J Impot Res (2004) 16:135–142.
  • Study Aims
    • This study was run alongside the previous one, assessing the efficacy of PT-141 in healthy subjects, with moderate to severe ED, who did not respond to Viagra.
    Study Design
    • This study was divided into two phases. Phase 1 saw 48 healthy males receive a dose of PT-141 or a placebo, while phase 2 saw eight healthy males with a history of ED, and who had not responded to Viagra receive the 4mg dose prior to the 6mg dose.
    • The doses were administered by sub cutaneous injection.
    • There was a dose-dependent increase in duration, at doses over 1mg in the phase 1 trial. There was decreased time to onset, with an average time of 37 minutes to first erection, at 10mg.
    • Phase 2A saw mean duration to base rigidity of 28 and 41 minutes for the respective 4mg and 6mg doses, compared to 6 minutes with placebo. The duration of rigidity more than doubled for 82% of patients receiving 4mg and 84% of patients receiving 6mg dose of PT-141.
    • PT-141 is safe and efficient in initiating erections. Further research is required to determine if PT-141 provides an additive or synergistic effect on PDE5 inhibitors.

Melanotan I & II

  • Wessells H, Levine N, Hadley ME, Dorr R, Hruby V. Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II. International Journal of Impotence Research (2000) 12, Suppl 4, S74-S79
  • Study Aim
    • This study sought to evaluate the efficacy of Melantotan II in the treatment of Erectile Dysfunction (ED).
    Study Design
    • The participants were all men aged 18-75 years of age with ED. They were divided into two different groups, based on whether they had psychogenic or organic ED. Each group had ten participants.
    • A double-blind, placebo-controlled crossover design was used. Participants received four subcutaneous injections of Melantotan II at a dose of 0.025 - 0.157 mg/kg. The order of administration was varied. Real-time RigiScan monitoring was used in the home situation to measure penile erection.
    • Participants were instructed to remain awake for the six-hour study period and avoid erotic stimuli. They recorded the number and duration of erectile events.
    • Seventeen participants recorded subjectively apparent erections after one or two Melantotan II injections. Erectile activity was reported following 69% of the Melantotan II injections and 2.4% of placebo injections.
    • Statistically significant differences were seen between Melantotan II and the placebo in the Rigiscan results, with a mean latency to first erection of 115 minutes, mean duration of rigidity of 41 minutes, with the organic group experiencing a shorter latency and rigidity period when compared to the psychogenic group.
    • Heightened sexual desire was seen after 68% of the Melantotan II injections in patients in the organic group.
    • Although not statistically significant, the magnitude and duration of erectile activity was greater in the psychogenic group.
    • The incidence of severe nausea and prolonged latency time may limit the clinical applications of Melantotan II, but it shows promise in being beneficial in ED patients. Further research is needed to determine the lowest effective dose of Melantotan II, especially in light of the side effects.


  • Magon N, Kalra S. The orgasmic history of oxytocin: Love, lust, and labor. Indian J Endocrinol Metab. 2011;15 Suppl 3(Suppl3):S156-S161
    • This is a review article that discusses the role that oxytocin has in, among other things, sexual activity, penile erection, and ejaculation.
    • An overview of the history of oxytocin and relevant research is provided.
    • The role it plays in love and social bonding is also addressed.
  • Carmichael MS, Humbert R, Dixen J, Palmisano G, Greenleaf W, Davidson JM. Plasma oxytocin increases in the human sexual response, Clin Endocrinol Metab. 1987 Jan;64(1):27-31.
    • Unfortunately, a full text version of this article is not available in the public domain. This is a limited summary based on the abstract.
    Study Aim
    • The study aimed to determine of oxytocin plasma levels change during a sexual response, and if so the pattern of temporary change.
    Study Design
    • The 9 men and 12 women who participated had plasma oxytocin levels measured before, during, and after self-masturbation.
    • Blood-pulse amplitude and electro-myographic activity were recorded continuously as an objective measure.
    • During sexual arousal in both men and women, plasma oxytocin levels increased. They were significantly higher than baseline during orgasm or ejaculation.
  • Blaicher W, Gruber D, Bieglmayer C, Blaicher AM, Knogler W, Huber JC, The role of oxytocin in relation to female sexual arousal, Gynecol Obstet Invest. 1999;47(2):125-6.
    • The full text article is available here. The website was unavailable at the time this report was written, so the summary is based on the abstract.
    Study Aim
    • This study aimed to understand the role of oxytocin in female arousal.
    Study Design
    • The 12 female participants had their blood serum oxytocin levels recorded before and after sexual stimulation.
    • The values of the blood serum oxytocin levels were significantly higher after sexual stimulation, compared to baseline.

Other Oxytocin Research

  • Dana A. Muin, Safoura Sheikh Rezaei, Max Tremmel-Scheinost, Mohamed Salama, Anton Luger, Michael Wolzt, Peter W. Husslein, Michaela Bayerle-Eder. Men's sexual response to female partner's intranasal oxytocin administration for hypoactive sexual desire disorder: an open prospective cohort study. Fertility and Sterility, 2017; 107 (3): 781. Neither the article or abstract were currently available.

Apomorphine (and in Combination with Tadalafil+)

  • Altwein J, E, Keuler F, U: Oral Treatment of Erectile Dysfunction with Apomorphine SL. Urol Int 2001;67:257-263.
  • Study Aims
    • The study aimed to evaluate the efficacy and tolerability of a dose-optimized regimen of apomorphine in the treatment of ED.
    Study Design
    • A two-week screening period evaluated the severity of ED in the study participants.
    • Participants then had a three-week period of dose optimization, with a starting dose of 2mg administered sub lingually. Patients were asked to make two attempts at intercourse per week. A sublingual tablet was to be placed under the tongue before each attempt. The investigator had the ability to increase the dose in 1mg increments to a maximum of 4mg.
    • For the following four weeks, participants were directed to take their individually optimized doses.
    • There were 849 participants, with their ages ranging from 31 to 78 years of age. The mean duration of ED was 5.7 years.
    • The mean percentage of attempts resulting in erections was 39.4%, as opposed to 13.1% at baseline.
    • The mean percentage of attempts resulting in intercourse was 38.3%, up from the baseline of 12.7%.
    • The median time to erection was 23 minutes, and the median duration 13 minutes.
    • Regardless of the cause or severity of the ED, a dose optimization period of three weeks with a starting dose of 2mg, titrated to a maximum of 4mg was found to be effective and well-tolerated.

Other Research into Apomorphine:

  • This article is a review article, but provides a useful summary of some of the research in this area. It also addresses apomorphine in combination with Tadalafil+ (and other PDE5 inhibitors).
    • Brock G. Oral Agents: First-Line Therapy for Erectile Dysfunction. European Urology (2002) 1(18), 12-18.
  • There was a considerable amount of research in this area that appears to be of relevance. However, this research could not be properly evaluated as access is restricted by paywalls. The research included:
    • Dula E, Keating W, Siami PF, Edmonds A, O'neil J, Buttler S. Efficacy and safety of fixed-dose and dose-optimization regimens of sublingual apomorphine versus placebo in men with erectile dysfunction. The Apomorphine Study Group. Urology. 2000;56(1):130-135.
    • Von Keitz AT, Ströberg P, Bukofzer S, Mallard N, Hibberd M. A European multicentre study to evaluate the tolerability of apomorphine sublingual administered in a forced dose-escalation regimen in patients with erectile dysfunction. BJU Int. 2002;89(4):409-415.
    • Dula E, Bukofzer S, Perdok R, George M; Apomorphine SL Study Group. Double-blind, crossover comparison of 3 mg apomorphine SL with placebo and with 4 mg apomorphine SL in male erectile dysfunction. Eur Urol. 2001;39(5):558-564.
  • There is also a body of research that addresses the treatment of ED in Parkinson's disease, with its inherent difficulties due to the involvement of dopamine systems in the disease process. This research was considered peripheral to the broader topic. This research included the following (full-text article was not available):
    • Sprenger F, Poewe W. Management of motor and non-motor symptoms in Parkinson's disease. CNS Drugs. 2013;27(4):259-272.


  • Fabbri A, Jannini EA, Gnessi L, et al. Endorphins in male impotence: evidence for naltrexone stimulation of erectile activity in patient therapy. Psychoneuroendocrinology. 1989;14(1-2):103-111.
  • Hypothesis
    • The hypothesis was that an alteration in central opioid tone is present in idiopathic impotence and is involved in the impairment of sexual behavior.
    Study Design
    • There were 30 participants aged 25-50 years of age, that had suffered idiopathic impotence for over a year.
    • Participants received either 50mg of naltrexone or a placebo on a random basis for two weeks. Sexual performance was assessed at days 0, 7, and 15. Sexual performance was assessed by the number of successful coitus per week.
    • All 15 participants experienced an increase in the number of morning or spontaneous penile erections (day 7 and 15).
    • The number of successful coitus per week increased in all participants (day 7 and 15).
    • Participants were also followed up at 2 months. At this follow-up, ten of the participant´s sexual performance had returned to baseline, while for five of the participants experienced a complete recovery of their sexual ability.
    • Given that no significant increases in plasma LDH, FSH or testosterone were observed, it seems likely that the positive results were a result of central system stimulation.
  • Sathe RS, Komisaruk BR, Ladas AK, Godbole SV. Naltrexone-induced augmentation of sexual response in men. Arch Med Res. 2001;32(3):221-226.
  • Study Aim
    Study Design
    • The study was a randomized, double-blind crossover involving 20 participants, all of whom were healthy and sexually active.
    • Between 18 and 22 hours after dosing, participants were instructed to view sexually explicit material in privacy for two hours, masturbating and having as many orgasms as they desired.
    • Three self-reported measures were used to evaluate the treatment; number of orgasms, intensity of sexual arousal, and orgasm intensity.
    • The mean number of orgasms under naltrexone was 3.4 compared to 2.6 under the placebo, with a total of 67 orgasms under naltrexone and 51 under the placebo.
    • The intensity of arousal was significantly greater when taking naltrexone, as was the orgasm intensity.
    • Endogenous opioids modulate orgasmic response and the perceived intensity of sexual arousal and orgasm in men. This creates a potential treatment option in cases of ED and inhibited sexual desire.

Thymosin Beta-4

  • No research relating to Thymosin Beta-4 could be located in the public domain.
  • The clinical trials' database did not have any trials involving the role of Thymosin Beta-4 in sexual functioning.

Research Strategy

To locate the relevant research, we adopted a five-pronged strategy. We first used common medical databases such as PubMed and NCMI, to search for the relevant articles. A search of the relevant peptide using its broader class, alternative identifiers, and trade and commercial names was undertaken as a second step. Our third strategy saw us review media publications and articles, as new research is often reported in the media. If we located any further research, we searched the title in medical databases to locate the article. A search of the clinical trial database was also completed to determine if there were any additional studies or research underway that was still to be completed. Our final strategy saw us use the reference section from the articles we had located to locate any additional relevant articles.

To obtain some of the full-text articles hidden behind paywalls, we employed two Google extensions, Unpaywall and Core Discovery. Both extensions are available for free online.

Wherever possible, if we identified additional research that had some minor relevance to the topic at hand or addressed the broader picture, we have included a citation and a brief explanation of why it is included. We have not summarized these articles, as, on many occasions, the full-text article was not available in the public domain.

Where a full-text article is not available, we have summarized the article based on the abstract. This was only done if all the options for obtaining a full-text article had been exhausted. We have noted this in the text when it has been necessary.

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