Dapoxetine + Sildenafil/Tadalafil: Does Combination Therapy Really Extend Time to Ejaculation?

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Ethical approval for this study was provided by the Rudraksha Hospital Ethical Committee, on 16 December 2021. All willing males with age between 30 and 65 years, having any duration of T2DM, with or without hypertension, and having a complaint relevant to sexual desire as diagnosed by the IIEF questionnaire were included in the study. IIEF questionnaire is used by physicians to diagnose the presence and severity of ED.

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[3] In addition, sexual dysfunction is another common complication of T2DM in both men and women. Erectile dysfunction (ED) is the well-established diabetes-related sexual dysfunction in men. In various studies, the prevalence of ED in men with diabetes is reported to lie between 20% and 67.4%. [4] However, it is important to note that the multifactorial pathophysiology of diabetes-induced ED and the need to consider multiple etiologies while addressing issues such as ED. The proposed mechanisms of ED in diabetic males include elevated advanced glycation end-products (AGEs), raised oxygen-free radicals, impaired nitric oxide (NO) synthesis, more endothelin B receptor binding sites, up-regulated RhoA/Rho-kinase pathway, neuropathic damage, and impaired cyclic guanosine monophosphate (cGMP)-dependent protein kinase-1.

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[5] AGEs accumulation result in vascular thickening, decreased elasticity, and atherosclerosis. Neuropathy plays a major role in the pathophysiology of ED in diabetes mellitus (DM). Next, neurophysiological tests such as nerve conduction studies, anal sphincter electromyography, heart rate variability testing, and quantitative sensory testing, have indicated abnormalities in men with diabetic ED with at least similar frequency as in men with neuropathic ED. [6] In addition, endothelial dysfunction leads to impaired activity of endothelial NO synthase (eNOS) and reduction in released NO. Decreased NO production by the penile arteries leads to decreased levels of cGMP, which is responsible for relaxation of the corpus cavernosum.

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[7] Furthermore, low testosterone levels are commonly found in men with T2DM with clinical symptoms of hypogonadism, including ED and decreased libido. Clearly, one cannot render any single molecular target treatment to be effective for managing the broad spectrum of cases that present ED-related complications. Moreover, early-stage targeted treatments are recommended for best results before irreversible changes occur. [8] The multifactorial etiology of ED calls for a multi-faceted approach for its treatment as well. The immediate action requires working on modifiable risk factors and lifestyle changes. [19] The five items are based on ability to identify the presence or absence of ED and on adherence to the National Institute of Health’s definition of ED.

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The following five items are included: erectile function (EF); orgasmic function (OF); sexual desire (SD); intercourse satisfaction (IS); and overall satisfaction (OS).

Overdose/Missed Dose

The purpose of such retrospective analysis was to evaluate the effect of parameters such as body mass index (BMI), HbA1c, testosterone, VitB12 and lipid profile parameters such as cholesterol, triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) on ED in men due to T2DM. The efficacy of Tadalafil alone and in combination with Dapoxetine in managing ED was evaluated and discussed. And the effect of comorbidities in individuals suffering from T2DM and ED was evaluated separately based on their BMI and the treatment groups. This was a bicentric, prospective, open-labelled, cross-sectional, observational study. Study centers were RIMS Super Specialty Hospital, Ahmedabad, and Rudraksha Multi-specialty Hospital, Bareja, situated in the state of Gujarat, India. Individuals with type-1 diabetes, chronic kidney disease, and those taking PDE-5 inhibitors were excluded from the study. Participants in the study were recruited from December 1, 2021 until March 31, 2022. Examination, history taking, anthropometric data, laboratory parameters, and questionnaire surveys were undertaken as a part of routine protocol. At the end of the demographic questionnaire, participants were requested to provide informed consent.

  • Dapoxetine is specifically designed for premature ejaculation issues.
  • Cialis improves blood flow to support ongoing erections.
  • Dapoxetine may not be suitable for men with liver problems.
  • Cialis has proven effective in enhancing sexual confidence.
  • Dapoxetine’s use should be limited to prescribed doses.
  • Cialis may cause a rare side effect called priapism.
  • Combining these drugs can intensify blood pressure fluctuations.
  • Always inform your doctor about other medications being taken.

Prospective data collection for metabolic disorders was done at tertiary care centers.

  • Dapoxetine is mainly prescribed for premature ejaculation treatment.
  • Cialis is a long-acting medication for erectile dysfunction.
  • Dapoxetine’s effects diminish within 3 hours of dosing.
  • Cialis can be effective for up to 36 hours post-dose.
  • Side effects of dapoxetine include nausea and dizziness.
  • Cialis side effects may include muscle pain and flushing.
  • Use these medications only under medical supervision.
  • Combining dapoxetine and Cialis may increase side effect risks.

The Tadalafil drug belongs to the class of PDE-5 inhibitors and Dapoxetine is a selective serotonin reuptake inhibitor.

Medical uses

The first line of pharmacologic therapy involves the use of phosphodiesterase 5 (PDE-5) inhibitors. [8] Sildenafil and vardenafil are the most-commonly used drugs to treat the ED but Tadalafil is more potent than other PDE-5 inhibitors. [9,10] Intracavernous injections, intraurethral suppositories, and vacuum erection devices comprise the second line of available treatment approaches for ED. [11,12,13] Thirdly, hormonal replacement therapy is also available for the individuals suffering from ED who do not respond to pharmacological therapies. [14] Lastly, penile implantation surgery remains a viable therapeutic option where medical management of ED is not possible.

Premature ejaculation

Besides ED, the use of Dapoxetine, a selective serotonin reuptake inhibitor, has been liquid cialis buy widely reported for the treatment of premature ejaculation in men. Dapoxetine is the first oral pharmacological agent indicated for the treatment of men aged 18–64 years with premature ejaculation. [16] In addition, the Sildenafil + Dapoxetine combination therapy has been reported to significantly improve the intravaginal ejaculation latency time values with mild and transient side effects. [17] Moreover, Dapoxetine has no clinically relevant pharmacokinetic interactions with Tadalafil or Sildenafil, and the drug combinations (Tadalafil + Dapoxetine or Sildenafil + Dapoxetine) are well-tolerated. This manuscript discusses the effect of physiological and metabolic parameters on sexual dysfunction, particularly ED in male T2DM subjects. The drugs were prescribed based on participant’s discretion. At baseline, the medical history of subjects including any previous medical conditions and other concomitant medication was recorded in a case record form followed by a general and systemic examination. Participants on either medication were followed up after 1 month of medication. The individual domain scores of IIEF were represented as boxplots to evaluate the effect of measured parameter such as BMI, HbA1c, testosterone, VitB12, cholesterol, triglyceride, HDL, and LDL. Similarly, the effect of treatments on IIEF scores was also represented. The statistical analysis was carried out using Microsoft Excel (Microsoft 365). For comparison of categorical variables, the χ2 test was used. For comparison of two groups, 2 tailed t-test with unequal variance was carried out. A significance level of 5% was used for considering the differences to be significant. Out of the 240 male T2DM subjects screened, 216 satisfied the inclusion criteria and were enrolled in the study. Subjects with age more than 40 years experienced ED almost two times as compared to those in the age groups of 30–39 years.

Safety and tolerability

The effect of physical and metabolic parameters on IIEF sub-domains namely erectile function; orgasmic function; sexual desire (SD); intercourse satisfaction; and overall satisfaction was evaluated. A statistical significance was evaluated using χ2 test or t-test. SD is most significantly lower in subjects with imbalanced physiological and metabolic characteristics including BMI, HbA1c, testosterone, VitB12, triglyceride, high-density lipoprotein, and low-density lipoprotein. Both Tadalafil and Tadalafil + Dapoxetine significantly improved almost all IIEF parameters without any pronounced effect of either. Similarly, both the treatments improved all the IIEF parameters for subjects with high BMI except for SD.

What should I know about tadalafil before using it?

In subjects with cardiac comorbidities, the use of either treatment significantly enhanced all the IIEF scores. The findings of this study outline the need of careful examination of sexual dysfunction in healthcare clinics for diabetic individuals. An imbalanced physiological and metabolic profile leads to ED in individuals with T2DM. Additionally, the presence of co-morbidities further elevates the odds of ED prevalence. The treatment with Tadalafil and Tadalafil + Dapoxetine drug combination shows promising results in improving the ED but a study with larger pool of subjects is needed to determine the additional benefits of Dapoxetine.

What should I do if I miss a dose of tadalafil?

Type-2 diabetes mellitus (T2DM) is one of the most common endocrine and metabolic disorders threatening global fitness. [1] Genetic predisposition, obesity, sedentary lifestyle, and an unhealthy diet are major risk factors for the development of T2DM and associated metabolic abnormalities resulting in insulin resistance. It manifests as hyperglycemia that occurs due to impaired insulin secretion or impaired insulin action or both. [2] The resulting metabolic imbalance often leads to the development of various micro- and macro-vascular complications. Micro-vascular complications comprise retinopathy, neuropathy, and nephropathy while macro-vascular complications can lead to coronary heart disease, stroke, and peripheral vascular disease. In general, the prevalence of ED increased with age among subjects having T2DM. Among the selected group, 53 individuals were prescribed either Tadalafil or Tadalafil + Dapoxetine drug combination as per their demand. The following effects were studied: (I) relationship between ED and BMI, HbA1c, testosterone, and VitB12; (II) effect of lipid profile parameters on ED; (III) effect of treatment on IIEF; (IV) role of BMI on the treatment efficacy; and (V) effect of co-morbidities on treatment outcome. Relationship between ED and BMI, HbA1c, testosterone, and VitB12 The effect of imbalance in parameters such as BMI, HbA1c, testosterone, and VitB12 caused by T2DM on ED was evaluated. The effect of these parameters was assessed by means of five domains of the IIEF questionnaire namely EF, OF, SD, IS, and OS. The significant differences (p < 0.05) are shown by horizontal brackets.

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Dr. med. Fabienne Gretener

Werdegang

Januar 2024 bis heute
Oberärztin SenoMed AG
Schwerpunktsweiterbildung gynäkologische Senology

März 2023 – Dezember 2023
Oberärztin, SenoMed AG Bern 20%

Januar 2023 – November 2023
Assistenzärztin Psychiatrie, Klinik Meissenberg Zug

Januar 2021 – November 2022
Assistenzärztin Gynecology und Geburtshilfe, Bürgerspital Solothurn

November 2019 – Oktober 2020
Assistenzärztin Gynecology und Geburtshilfe, Kantonsspital Aarau

Januar 2017 – Juli 2019
Assistenzärztin Gynecology und Geburtshilfe, Kantonsspital Olten

Paul Laszlo Bernhard

Werdegang

Jan 2024 bis heute
Facharzt SenoMed AG – Brustzentrum Bern Biel

Aug 2019 – Dez 2023
Oberarzt Frauenklinik und Brustzentrum Bürgerspital, Solothurn, Schwerpunktweiterbildung operative Gynecology und Geburtshilfe sowie Senology

Mai 2019 Facharzttitel Gynecology & Geburtshilfe

Apr 2016 – Jul 2019
Arzt in Weiterbildung, Inselspital Bern, Universitätsklinik für Frauenheilkunde

Dez 2014 – Apr 2016
Arzt in Weiterbildung, Kantonsspital Baden

Sep 2012 – Sep 2014
Arzt in Weiterbildung, Universitätsklinikum Carl Gustav Carus, Dresden

Feb 2012 – Sep 2012
Arzt in Weiterbildung, Universitätsfrauenklinik Leipzig

Nov 2011 Approbation zum Arzt

2005 – 2011
Studium der Humanmedizin an der Charité, Universitätsmedizin Berlin

Dr. med. Patrizia Sager

Werdegang

Okt 2023 bis heute
Leiterin Weiterbildungsstätte gynäkologische Senology

Feb 2018 – bis heute
Leiterin Brustzentrum Bern Biel
Practiceinhaberin SenoMed AG

Nov 2017 – bis heute
Belegärztin Salem-Spital Bern

Jan 2013 – Okt 2017
Leitung Senology Brustzentrum Frauenklinik Universitätsspital Insel, Bern

Jan 2012 – Dez 2012
Oberärztin Gynecology / Geburtshilfe, Frauenklinik Universitätsspital Insel, Bern

Nov 2010 – Dez 2011
Leitende Ärztin Gynecology und Geburtshilfe, Frauenklinik Rheinfelden (DE)

Nov 2009 – Okt 2010
Oberärztin Gynecology und Geburtshilfe, Kantonsspital Liestal

Jan 2009 – Okt 2009
Oberärztin i.V. Gynecology und Geburtshilfe, Regionalspital Interlaken

Jun 2008 – Dez 2008
Assistenzärztin Gynecology und Geburtshilfe, Regionalspital Interlaken

Aug 2007 – Mai 2008
Assistenzärztin Gynecology und Geburtshilfe, Universitätsspital Zürich

Feb 2007 – Jun 2007
Oberärztin Gynecology und Geburtshilfe, Universitätsspital Groote Schuur, Kapstadt, Südafrika

Jan 2004 – Dez 2006
Assistenzärztin Gynecology und Geburtshilfe, Regionalspital Thun

Jan 2003 – Dez 2003
Assistenzärztin Chirurgie und Orthopädie, Regionalspital Thun

Schulen, Studium & Diplome

2023
Schwerpunkt gynäkologische Senology

2014
Diplom Senology SGGG

2013
Diplom Senology: European Academy of Senology

2010
FMH Gynecology und Geburtshilfe inkl. Schwerpunkt operative Gynecology

2003
Promotion

2002
Staatsexamen in Humanmedizin

1996 – 2002
Humanmedizinstudium Universitätsspital Basel

Mitglied- und Partnerschaften

  • Schweizerische Gesellschaft für Gynecology und Geburtshilfe SGGG
  • Schweizerische Gesellschaft für Senology SGS
  • Mitglieder Arbeitsgemeinschaft Gynäkologische Onkologie AGO, Schweiz
  • European Academy of Senology EAoS
  • SAKK Project-Group breast cancer
  • Schweizerische Gesellschaft für Ultraschall in der Medizin SGUM
  • Verbindung der Schweizer Ärzte und Ärztinnen FMH
  • Society of women in senology SWIS
  • Vorstandsmitglied Ärztenetzwerk Bern