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ORIGINAL ARTICLE
Year : 2023 | Volume
: 14
| Issue : 1 | Page : 48-55
The efficacy of Tadalafil and Tadalafil + Dapoxetine in managing sexual dysfunction in individuals with type-2 diabetes mellitus: A clinical study
Vipul Chavda1, Santosh Jha2, Tejal R Gandhi3, Anjali B Patel3, Hiren Raninga3, Amol Chaudhari4, Dhruvi Hasnani1
1 Department of Diabetology, Rudraksha Institute of Medical Sciences, Ahmedabad, Gujarat, India
2 Department of Internal Medicine, Rudraksha Institute of Medical Sciences, Ahmedabad, Gujarat, India
3 Department of Pharmacology, Anand, Gujarat, India
4 Department of Science, Neovation Consultancy Services Pte. Ltd., Singapore, Singapore
Correspondence Address:
Dr. Dhruvi Hasnani
Department of Diabetology, Rudraksha Institute of Medical Sciences, Maninagar, Ahmedabad 380050, Gujarat
India
Source of Support: None, Conflict of Interest: None
DOI: 10.4103/jod.jod_123_22
Objective: The present study was aimed to evaluate effect of metabolic parameters on erectile dysfunction (ED) in individuals with type-2 diabetes mellitus (T2DM) and to assess the efficacy of Tadalafil and Tadalafil + Dapoxetine combination. Materials and Methods: A prospective, observational, cross-sectional, bicentric study included 216 males with T2DM who are not treated with phosphodiesterase 5 inhibitors and without chronic kidney disease. The data were obtained from demographic questionnaire, clinical laboratory reports of glycometabolic parameters namely body mass index (BMI), hemoglobin A1c (HbA1c), testosterone, vitamin B12 (VitB12), and lipid profile and analyses of the International Index of Erectile Function (IIEF) questionnaire. 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. Result: 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. In subjects with cardiac comorbidities, the use of either treatment significantly enhanced all the IIEF scores. Conclusion: 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.
Keywords: Effect of comorbidities, erectile dysfunction, international index of erectile function, metabolic assessment, type-2 diabetes mellitus
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.[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.[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.[7] Furthermore, low testosterone levels are commonly found in men with T2DM with clinical symptoms of hypogonadism, including ED and decreased libido.[1]
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. 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.[15]
Besides ED, the use of Dapoxetine, a selective serotonin reuptake inhibitor, has been 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.[18]
This manuscript discusses the effect of physiological and metabolic parameters on sexual dysfunction, particularly ED in male T2DM subjects. 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.
Materials and MethodsStudy design
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. Ethical approval for this study was provided by the Rudraksha Hospital Ethical Committee, on 16 December 2021.
Eligibility criteria
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.[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. The following five items are included: erectile function (EF); orgasmic function (OF); sexual desire (SD); intercourse satisfaction (IS); and overall satisfaction (OS). 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.
Data collection
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. Prospective data collection for metabolic disorders was done at tertiary care centers. The IIEF questionnaire is added as supplementary information file.
Drugs
The Tadalafil drug belongs to the class of PDE-5 inhibitors and Dapoxetine is a selective serotonin reuptake inhibitor. The drugs were prescribed based on participant’s discretion.
Evaluation of drug efficacy
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.
Statistical analysis
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.
ResultsOut 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. 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. Analysis of the participant responses to the IIEF questionnaire, as shown in [Figure 1], indicates that SD and OS scores were significantly low in subjects with BMI higher than cut-off (>23 kg/m2) with respect to subjects with BMI less than or equal to cut-off (≤23 kg/m2). A cut-off BMI of 23 kg/m2 was considered according to the Asian standards.[20] Subjects having high (>7.5%) compared to normal HbA1c reported reduced SD and OS scores. Subjects with low (<400 ng/dL) compared to normal testosterone levels reported reduced OF and SD scores. Subjects having low (<300 pg/mL) compared to normal VitB12 reported a significant reduction in SD scores. These findings suggest a direct correlation between an unbalanced glycometabolic profile and sexual dysfunction in individuals with T2DM.
Figure 1: Glycometabolic parameters and their effect on IIEF scores. The effect of BMI (cut-off: 23 kg/m2, above cut-off: >23 kg/m2), HbA1c (normal: <7.5%, high: >7.5%), testosterone (low: 0–400 ng/dL; normal: 400–1000 ng/dL), and VitB12 (low: 0–300 pg/mL; normal: 300–2000 pg/mL) on sexual dysfunction in the subjects was measured based on IIEF scores. p < 0.05 was considered statistically significant and indicated with a horizontal bracketEffect of lipid profile on ED
The effects of lipid profile parameters of the subjects on sexual dysfunction were evaluated. [Figure 2] depicts that there was no significant difference in IIEF parameters when compared at normal (0–200 mg/dL) or high (200–400 mg/dL) cholesterol levels. In terms of elevated triglyceride levels (>150 mg/dL), SD score was reported to be significantly reduced as compared to the subjects with triglyceride levels in the normal range (0–150 mg/dL). The subjects with low levels of HDL (0–40 mg/dL) compared to normal as well as high levels of LDL (100–220 mg/dL) compared to normal reported a significant reduction in SD and OS scores.
Figure 2: Lipid profile parameters and their effect on IIEF scores. The effect of cholesterol (normal: 0–200 mg/dL; high: 200–400 mg/dL), triglyceride (normal: 0–150 mg/dL; high: >150 mg/dL), HDL (low: 0–40 mg/dL; normal: 40–60 mg/dL), and LDL (normal: 0–100 mg/dL; high: 100–220 mg/dL) on sexual dysfunction in subjects was measured based on reported IIEF scores. p < 0.05 was considered statistically significant and indicated with a horizontal bracketEffect of treatment on IIEF
The subjects, who were on Tadalafil or the combination of Tadalafil + Dapoxetine, were counselled with the validated IIEF questionnaire for ED at baseline and at follow-up. It was seen that the individuals on Tadalafil reported significant improvement in all the IIEF parameters at the follow-up with respect to the baseline [Figure 3]A. In addition, individuals on Tadalafil + Dapoxetine reported significant improvement in all domains of IIEF except SD [Figure 3]B. Thus, if we compare the effects of both, Tadalafil versus Tadalafil + Dapoxetine drug combination on change in IIEF scores at the follow-up, both groups had similar effect on ED and there was no significant difference in the IIEF parameters when compared at follow-up [Figure 3]C.
Figure 3: Effect of treatment on IIEF scores. Efficacy of (A) Tadalafil or (B) the combination of Tadalafil + Dapoxetine in the treated individuals based on IIEF scores at baseline and at follow-up. (C) A comparison of change in IIEF scores at follow-up with either Tadalafil or Tadalafil + Dapoxetine drug combination. p < 0.05 was considered statistically significant and indicated with a horizontal bracketRole of BMI on the treatment efficacy
BMI has a significant effect on the IIEF parameters as seen from this study [Figure 1] as well as previous reports.[21] Therefore, the effect of BMI at cut-off and above cut-off was evaluated for treated individuals at the baseline and at follow-up. [Figure 4] shows that Tadalafil-treated individuals having cut-off or below cut-off BMI showed significant improvement only in OS score. Individuals treated with Tadalafil + Dapoxetine who were also having cut-off or below cut-off BMI showed no significant improvement in any of the IIEF scores. Tadalafil and Tadalafil + Dapoxetine combination treatment improved all the IIEF scores for individuals with above cut-off BMI except for SD values.
Figure 4: Effect of BMI and treatment on IIEF scores at baseline and follow-up of treated subjects. At normal BMI (cut-off or below cut-off), the effect of (A) Tadalafil, and (B) Tadalafil + Dapoxetine on IIEF scores. At high BMI (above cut-off), the effect of (C) Tadalafil, and (D) Tadalafil + Dapoxetine on IIEF scores. p < 0.05 was considered statistically significant and indicated with a horizontal bracketEffect of co-morbidities on treatment outcome
The effect of comorbidities on ED is not well understood because co-morbidities such as hypertension, dyslipidemia, and coronary artery disease can lead to other health problems that can also impact erectile function.[22] Therefore, the effect of comorbidities at baseline was compared with the follow-up values of IIEF parameters of all the treated subjects. [Figure 5] depicts that except for the SD values in individuals without co-morbidities (C–), all other IIEF values significantly improved after the treatment (Tadalafil or Tadalafil + Dapoxetine). On the other hand, in individuals with comorbidities (C+), the effect of both the medications was positive on treatment of ED as seen by the significant improvement of all the IIEF scores.
Figure 5: Effect of comorbidities on treatment. Evaluation of changes in IIEF scores at baseline versus at follow-up in individuals with (C+) and without (C–) comorbidities, who were treated with either Tadalafil or Tadalafil + Dapoxetine drug combination. p < 0.05 was considered statistically significant and indicated with a horizontal bracket Discussion DM is considered a possibly life-threatening metabolic disorder with mortalities reported to be associated with complications such as cardiovascular diseases, kidney failure, retinopathy, nephropathy, and neuropathy.[3] Additionally, ED, reduced sexual desire, orgasmic disorder, and retrograde ejaculation are also a sub-set of complications of variable incidence in men suffering from DM.[1] The objective of the present study was to characterize the major sexual dysfunctions in a single diabetic population, and their inter-associations with other clinical variables and comorbidities. The study investigated the frequency of IIEF scores in 216 men suffering from T2DM. Approximately 41% of the subjects included in this study reported lower than normal SD scores which is a clear indication of ED. This finding resonated with reports published in several previous studies. Two studies, one from the Netherlands and another from the United States indicated that 41.3% and more than 50% of the subjects respectively reported prevalence of ED.[23],[24] Thus, low SD is a clear indicator of ED in individuals with DM.
The findings of the current study showed that age is significantly associated with ED in individuals with T2DM which is known from the fact that the prevalence of severe ED increases with age.[25] Secondly, obesity is also one of the risk factors for developing ED.[26] Among all subjects enrolled in the current study, 187 (86.6%) had a BMI of more than cut-off of 23 kg/m2 and these subjects showed significantly lower SD values as compared to the individuals with cut-off or lower than cut-off BMI. A similar observation was also made for other clinical parameters except cholesterol. Reported SD values are significantly lower in subjects who also exhibit imbalanced metabolic profile with high HbA1c, low testosterone, low VitB12, high triglyceride, low HDL, and high LDL. The lipid profile is also a pressing cause of concern in aggravating ED. Findings in this study demonstrate that an imbalance in triglycerides, HDL, and LDL affect the OS scores significantly. Interesting to note is the fact that a raised cholesterol level does not by itself have a direct adverse effect on any of the five domains of the IIEF scores.
Next, the investigation demonstrates that the prevalence of ED using the IIEF is (more than 50%) higher in men with DM as observed from the HbA1c results. Among 216 participants with sexual dysfunction enrolled in this study, 136 (62.9%) had a higher HbA1c level (7.6–16%). Higher HbA1c levels are associated with ED which was also observed in another study.[25] In addition, testosterone hormone is responsible for normal sexual functioning such as erection and for sexual desire or libido. Among all study participants, 61.9% were found to have a low level of testosterone. Furthermore, the effect of hypogonadism on reduced libido and DM is supported by several studies.[27],[28] Besides, conditions such as metabolic syndrome and atherogenic dyslipidemia are also associated with ED among diabetic men.[29] Among the study participants, 57.8% had high triglyceride levels and 25.4% of subjects had low levels of HDL.
This study also presents noteworthy findings when the participants were subjected to Tadalafil or the combination of Tadalafil + Dapoxetine. There was no indication of superiority of either. Both Tadalafil and Tadalafil + Dapoxetine improved most of the IIEF parameters. Thus, there appears to be no masking effect on the efficacy of Tadalafil when it is used in combination with Dapoxetine. Moreover, the Tadalafil + Dapoxetine combination improved all the IIEF parameters for subjects with high BMI except for SD. In subjects with co-morbidities, the use of either Tadalafil or Tadalafil + Dapoxetine drug combination was shown to significantly enhance all the IIEF scores, suggesting a strong correlation between comorbidities and ED.
ConclusionThe findings of the present study highlight the high prevalence of ED in men suffering from T2DM. An imbalanced physiological profile, such as higher BMI, higher HbA1c, lower testosterone, disturbed lipid profile, and a lower VitB12 level is reported to be major contributors to ED. In addition to this, the presence of comorbidities such as hypertension, dyslipidemia, and coronary artery disease further elevates the odds of developing ED. The treatment of individuals with T2DM with Tadalafil and Tadalafil + Dapoxetine drug combination shows promising results in improving ED, as analyzed using the IIEF questionnaires. However, no clear advantage of combination of the two drugs was observed. This study lays the foundation of long-term prospective clinical studies to validate the efficacy of using Tadalafil + Dapoxetine drug combination in managing ED in individuals with T2DM. The findings of this study also outline the pressing need of careful examination of sexual dysfunction in healthcare clinics for diabetic individuals. Increased awareness through routine screening for ED can contribute to the timely diagnosis and effective treatment of ED especially in elderly population.
Acknowledgments
Vibhuti Jain Rana, Nishtha Singh, and Pusala Lakshmi Prasanna from Neovation Consultancy Services Pte. Ltd., Singapore, for assisting with statistical analysis and manuscript revision.
Financial support and sponsorship
Nil.
Conflicts of interest
The authors of this study do not have any conflicts of interest with publication of the manuscript or an institution or product that is mentioned in the manuscript and/or is important to the outcome of the study presented. Dr. Amol Chaudhari is also a part of the scientific department at Neovation Consultancy Services Pte. Ltd., Singapore.
Author contributions
Dr. Vipul Chavda conceived the idea and design for the study and overlooked the entire study until completion. Dr. Santosh Jha made major contributions in drafting the manuscript and statistical analysis. Dr. Tejal Gandhi and Anjali Patel conducted manuscript editing and reviewing. Literature search and clinical data collection was done by Hiren Raninga. Dr. Amol Chaudhari and Dr. Dhruvi Hasnani performed statistical analysis on the collected data, wrote and reviewed the manuscript.
Supplementary InformationIIEF Questionnaire
Q1. How often were you able to get an erection during sexual activity?0 No sexual activity1 Almost never or never2 A few times (less than half the time)3 Sometimes (about half the time)4 Most times (more than half the time)5 Almost always or alwaysQ2. When you had erections with sexual stimulation, how often were your erections hard enough for penetration?0 No sexual activity1 Almost never or never2 A few times (less than half the time)3 Sometimes (about half the time)4 Most times (more than half the time)5 Almost always or alwaysQ3. When you attempted intercourse, how often were you able to penetrate (enter) your partner?0 Did not attempt intercourse1 Almost never or never2 A few times (less than half the time)3 Sometimes (about half the time)4 Most times (more than half the time)5 Almost always or alwaysQ4. During sexual intercourse, how often were you able to maintain your erection after you had penetrated (entered) your partner?0 Did not attempt intercourse1 Almost never or never2 A few times (less than half the time)3 Sometimes (about half the time)4 Most times (more than half the time)5 Almost always or alwaysQ5. During sexual intercourse, how difficult was it to maintain your erection to completion of intercourse?0 Did not attempt intercourse1 Extremely difficult2 Very difficult3 Difficult4 Slightly difficult5 Not difficultQ6. How many times have you attempted sexual intercourse?0 No attempts1 One to two attempts2 Three to four attempts3 Five to six attempts4 Seven to ten attempts5 Eleven or more attemptsQ7. When you attempted sexual intercourse, how often was it satisfactory for you?0 Did not attempt intercourse1 Almost never or never2 A few times (less than half the time)3 Sometimes (about half the time)4 Most times (more than half the time)5 Almost always or alwaysQ8. How much have you enjoyed sexual intercourse?0 No intercourse1 No enjoyment at all2 Not very enjoyable3 Fairly enjoyable4 Highly enjoyable5 Very highly enjoyableQ9. When you had sexual stimulation or intercourse, how often did you ejaculate?0 No sexual stimulation or intercourse1 Almost never or never2 A few times (less than half the time)3 Sometimes (about half the time)4 Most times (more than half the time)5 Almost always or alwaysQ10. When you had sexual stimulation or intercourse, how often did you have the feeling of orgasm or climax?1 Almost never or never2 A few times (less than half the time)3 Sometimes (about half the time)4 Most times (more than half the time)5 Almost always or alwaysQ11. How often have you felt sexual desire?1 Almost never or never2 A few times (less than half the time)3 Sometimes (about half the time)4 Most times (more than half the time)5 Almost always or alwaysQ12. How would you rate your level of sexual desire?1 Very low or none at all2 Low3 Moderate4 High5 Very highQ13. How satisfied have you been with your overall sex life?1 Very dissatisfied2 Moderately dissatisfied3 Equally satisfied & dissatisfied4 Moderately satisfied5 Very satisfiedQ14. How satisfied have you been with your sexual relationship with your partner?1 Very dissatisfied2 Moderately dissatisfied3 Equally satisfied & dissatisfied4 Moderately satisfied5 Very satisfiedQ15. How do you rate your confidence that you could get and keep an erection?1 Very low2 Low3 Moderate4 High5 Very high BackgroundThe 15-question International Index of Erectile Function (IIEF) Questionnaire is a validated, multidimensional, self-administered investigation that has been found useful in the clinical assessment of erectile dysfunction and treatment outcomes in clinical trials.[19] A score of 0-5 is awarded to each of the 15 questions that examine the five domains of male sexual function: erectile function (EF)), orgasmic function (OF), sexual desire (SD), intercourse satisfaction (IS), and overall satisfaction (OS).
References
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