Effects of Two Allisartan Isoproxil‐Based Antihypertensive Therapies on Sexual Function and Blood Pressure in Male Hypertensive Patients: A Single‐Center, Open‐Label, and Randomized Controlled Trial

ABSTRACT

This study evaluated the effects of allisartan isoproxil combined with amlodipine besylate tablets (Group A+C) or metoprolol succinate extended‐release tablets (Group A+B) on sexual function and nighttime blood pressure (nBP) in 130 male patients with essential hypertension (EH). Patients were randomized to two groups. After 6‐month, the IIEF‐15 total score (ITS) of sexual function significantly improved in Group A+C (p = 0.015), including intercourse satisfaction (IS) (p = 0.003), orgasmic function (OF) (p = 0.021), and overall satisfaction (OS) (p = 0.019), while erectile function (EF) (p = 0.081) and sexual desire (SD) (p = 0.08) were unchanged. In contrast, the ITS was decreased (p = 0.008), including EF (p = 0.005), IS (p = 0.048), SD (p = 0.003), and OS (p = 0.010), but OF remained unchanged (p = 0.076) in Group A+B. Between‐group comparisons confirmed significant differences across IIEF‐15 domains (all p < 0.05). Compared to baseline, office systolic BP (OSBP), office diastolic BP (ODBP), nighttime average SBP (nSBP), and nighttime average DBP (nDBP) were significantly reduced at 6 months in two groups (all p < 0.05). Although nSBP fall (nSBPF) (p = 0.010) and nDBP fall (nDBPF) (p = 0.002) significantly increased in Group A+C. In Group A+C, the nighttime‐daytime BP fall ratio of SBP was 1.04 (0.45, 1.70) and that of DBP was 1.13 (0.38, 1.44) after treatment, with a median value > 1, indicating that nBP fall after treatment was greater than dBP fall. Compared to Group A+B, ODBP (difference = −4.00 mmHg, 95% CI [−7.64, −0.36], p = 0.032), daytime average DBP (difference = −5.47 mmHg, 95% CI [−10.05, −0.79], p = 0.023) and 24‐h average DBP (difference = −5.77 mmHg, 95% CI [−10.31, −1.24], p = 0.014) decreased more significantly in Group A+C, nDBPF increased significantly (difference = 4.99 mmHg, 95% CI [0.04, 9.93], p = 0.048), and the decrease in the nighttime‐daytime BP fall ratio of SBP and DBP was higher (p < 0.05). It was concluded that combined antihypertension of allisartan isoproxil with amlodipine besylate tablets improved sexual function in male hypertensive patients in terms of the ITS, IS, OF, and OS, but there was no significant improvement in EF and SD. Both combined antihypertensive regimens were effective in lowering BP, but allisartan isoproxil combined with amlodipine besylate tablets demonstrated more advantageous in lowering DBP and nBP.

1. Introduction

Hypertension is one of the world's largest public health problem and the leading modifiable risk factor for cardiovascular disease and all‐cause mortality [1]. By 2025, global hypertension may reach 1.5 billion [2]. Chronic hypertension not only causes structural or functional changes or even target organ damage [3] but also is closely associated with one of the most frequently overlooked male health concerns: sexual dysfunction [4]. As the WHO points out, sexual health is an important component of overall health and    a key manifestation of a good quality of life. Sexual dysfunction can undermine men's self‐esteem, self‐confidence, and emotions, significantly affecting their physiopsychological health and work performance, and interpersonal relationships. It may also trigger anxiety or depressive symptoms, further diminishing the quality of life for both patients and their partners. Epidemiological studies have demonstrated that the prevalence of erectile dysfunction (ED) in men with hypertension is nearly twice as high as that in people with normal BP, underscoring the need for greater attention to sexual health in this population [5].

Compared with untreated patients, patients receiving antihypertensive treatment are more likely to experience sexual dysfunction, suggesting a potential negative impact of treatment on sexual function [5]. Antihypertensive treatment‐associated sexual dysfunction, especially ED, reduces medication adherence and willingness to take long‐term medication in male patients, leading to substandard control of BP, aggravating patients’ sexual dysfunction, and forming a vicious circle [6]. Therefore, the rational selection of antihypertensive drugs is the primary consideration for younger or more sexually demanding male hypertensive patients, as it not only controls better BP but also enhances the quality of life and overall health for patients and their partners. Different antihypertensive drugs have different effects on sexual function. Diuretics and conventional beta‐blockers may trigger or aggravate sexual dysfunction, while angiotensin converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), calcium channel blockers (CCBs), or vasodilatory beta‐blockers may have neutral or even beneficial. The relationship between beta‐blockers and sexual dysfunction remains controversial. Evidence indicate that older beta‐blockers (e.g., propranolol) predispose to sexual dysfunction, while newer beta‐blockers (e.g., nebivolol and celiprolol) have lesser negative effects. A recent crossover‐designed RCT showed that, compared to metoprolol, the novel third‐generation, highly selective β1‐blocker nebivolol significantly improved ED by promoting NO synthesis [7]. The meta‐analysis confirmed that nebivolol significantly improved erectile function (EF) compared to non‐vasodilating β‐blockers (OR = 2.92, 95% CI 1.3–6.5) [8].

As a novel nonpeptide ARB, allisartan isoproxil  has its affinity for AT1R  that is 1000 times higher than that AT2R, blocking the physiological effects associated with angiotensin II [9, 10]. Several studies have shown that alisatan isoproxil has a long half‐life, 24‐h antihypertensive coverage, a high trough‐to‐peak ratio, and a high smoothness index for long‐lasting, smooth  BP control. In addition, it can correct BP patterns and circadian rhythms, making it a promising antihypertensive agent [9, 10, 11, 12]. Currently, guidelines recommend combination therapy as an initial antihypertensive strategy, knowing that drug combination can leverage the complementarity of mechanisms, produce additional or synergistic effects, faster BP control, reduce dosage, reduce adverse effects, and improve adherence and persistence. This approach can help establish a virtuous circle, thus improving the therapeutic efficacy and hypertension control rates [1, 13].

Previous studies have demonstrated that ARBs such as valsartan, irbesartan, and olmesartan medoxomil can improve sexual function by increasing the NO level, malondialdehyde concentration, and endothelial nitric oxide synthase, and inhibiting oxidative stress as well [5, 14]. However, few studies have reported the effect of using an allisartan isoproxil‐based combination as an initial antihypertensive therapy on sexual function in male hypertensive patients. This real‐world study aimed to evaluate the effect of allisartan isoproxil‐based combination antihypertensive therapy on sexual function and BP in hypertensive patients. Additionally, it sought to clarify whether this treatment can simultaneously improve the patient's quality of life, providing evidence to support the rational clinical use of antihypertensive medications

2. Participants and Methods

2.1. Participants and Ethical Approval

This is a single‐center, prospective, open‐label, parallel‐controlled, randomized study approved by the Ethics Committee of the Second Hospital of Lanzhou University (Lanzhou, China), conducted in accordance with the Declaration of Helsinki (2022A‐534). The trial was registered in the Chinese Clinical Trial Registry (Registration No.: ChiCTR2500106035). Eligible participants included male outpatients and inpatients with essential hypertension (EH) who were admitted to the Cardiovascular Department of the Second Hospital of Lanzhou University from 2022 to 2023. Subjects were enrolled based on predefined inclusion and exclusion criteria.

2.2. Inclusion Criteria

The inclusion criteria conformed to the diagnostic criteria for EH in the Chinese Guidelines for Hypertension Prevention and Treatment 2018 Revision [15], including male patients aged 18–75 years who had a steady sexual activity at least once a week or more. All participants were able to think independently and decision‐making. All participants understood the study procedures and signed the informed consent form.

2.3. Exclusion Criteria

The exclusion criteria included patients with secondary hypertension, acute heart failure (New York Heart Association Class II or above), acute myocardial infarction, severe heart valve disease, severe peripheral vascular disease, severe or greater anemia, diabetes mellitus, malignant neoplasm, hyper‐ or hypothyroidism, a history of severe cerebral vascular accidents, multiple sclerosis, epilepsy, Parkinson's disease, Alzheimer's disease, spinal cord injuries, genital deformities, abnormalities of sexual development, abnormal sex hormone production, Peyronie's disease, primary hypogonadism, a history of urogenital surgery, severe hepatic or renal insufficiency (ALT, AST, or TBIL >2 times the upper limit of the normal range), hyperkalemia, mental illness, a history of alcohol or drug abuse, a history of allergy, or contraindications to drug ingredients.

2.4. Drug Administration Procedures

Using a randomization list generated by the validated automatic random number generator, the patients were randomized to receive allisartan isoproxil tablets (240 mg/tablet) combined with amlodipine besylate tablets (5 mg/tablet, trade name: Norvasc), or allisartan isoproxil tablets (240 mg/tablet) combined with metoprolol succinate sustained‐release tablets (47.5 mg/tablet). After 4‐week treatment, the dose of amlodipine besylate tablets was gradually increased from 5 to 10 mg or metoprolol succinate sustained‐release tablets from 47.5 to 95 mg if BP remained above target. Baseline demographic and clinical characteristics were recorded, including age, office BP (OBP), body mass index (BMI), smoking, alcohol consumption, physical activity, fasting blood glucose, renal function, and lipid parameters.

2.5. IIEF‐15 Questionnaire

Using the IIEF‐15 questionnaire, sexual function was assessed in terms of the five domains scores, including EF, intercourse satisfaction (IS), orgasmic function (OF), sexual desire (SD), and overall satisfaction (OS) [5, 14].

2.6. BP Measurement Method

OBP was measured using a certified upper‐arm electronic sphygmomanometer (Omron, HEM‐9200T). Before measurement, patients were instructed to avoid smoking, drinking coffee and tea for at least 30 min, empty their bladder, and rest quietly for 3–5 min with their upper arms at heart level. Measurement was made at least twice with an interval of 1–2 min between, and the mean value was used for analysis. If the difference between the first two readings exceeded 5 mmHg, a third measurement was performed and the mean value of the three readings was used for analysis [15]. OBP parameters included office systolic BP (OSBP) and office diastolic BP (ODBP).

2.7. Ambulatory BP Monitoring (ABPM)

ABPM was performed by a professional from the Cardiac Functional Examination Unit. Patients were fitted with a standardized ambulatory sphygmomanometer (model TM‐2430). They were advised to maintain their usual daily activities while avoiding strenuous activities and fatigue. During each automatic measurement, they were advised to keep their arms relaxed and still. Sleep and wake times were recorded on individual diary cards. ABPM parameters included daytime average systolic BP (dSBP), daytime average diastolic BP (dDBP), nighttime average SBP (nSBP), nighttime average DBP (nDBP), 24‐h average systolic BP (24hSBP), 24‐h average diastolic BP (24hDBP), nighttime systolic BP fall (nSBPF), and nighttime diastolic BP fall (nDBPF). Nighttime BP fall rate = (daytime average BP–nighttime average BP)/daytime average BP. Nighttime–daytime BP fall ratio = (nighttime BP fall/daytime BP fall), a ratio close to 1 indicates that nocturnal and daytime BP drops are similar magnitude, and a value >1 indicates that nighttime blood pressure (nBP) fall is greater than dBP fall. Nighttime BP fall and daytime BP fall refer to the decrease value in nBP and dBP compared to the level before treatment.

2.8. Statistical Methods

The sample size was estimated based on the prevalence of ED reported in the literature, using the following formula: n = μ_{α /2} ² p (1 − p)/d ², where n: required sample size, α = 0.05, μ_{α /2} = 1.96, p: prevalence of ED, d: admissible error, set as 20% of p. According to a previous study, the prevalence of ED in hypertensive men in China was 46.32% [16], the calculated sample size was n = μ_{α /2} ² p(1 − p)/d ² = 111.

All statistical analyses were performed using SPSS version 22.0 software. The normality of continuous variables were tested using the Shapiro–Wilk test, and those conforming to normal or approximately normal distribution were expressed using the mean ± standard deviation (x ± s), and those conforming to skewed distribution were expressed using median and interquartile spacing [M (P25, P75)], and categorical variables was described using frequencies or percentages (%). For between‐group comparisons of continuous data, the independent t test was used for normal distribution and homogeneity of variance, and the corrected t test was used for heterogeneity of variance. Skewed distribution was determined using the Wilcoxon rank‐sum test. For within‐group comparisons, the normally distributed data were determined using a paired t test, and the skewed distribution was analyzed using a paired rank‐sum test. Intergroup comparisons of count data were compared using the Chi‐squared test and Fisher's exact test. All statistical tests were two‐sided test, and p < 0.05 was considered statistically significant.

3. Results

3.1. Patient Screening

Of 148 patients with EH, 18 patients failed the screening. A total of 130 patients were enrolled and randomized to Group A+C (n = 68) or Group A+B (n = 62). Five patients in Group A+C and 6 patients in Group A+B were lost to follow up, including one death due to severe COVID‐19 pneumonia. The screening process is illustrated in Figure 1.

FIGURE 1.

Research flowchart. Note: Group A+C, allisartan isoproxil tablets combined with amlodipine besylate tablets; Group A+B, allisartan isoproxil tablets combined with metoprolol succinate sustained‐release tablets.

3.2. Baseline Characteristics

There were no statistically significant differences in age, BMI, OSBP, ODBP, duration of hypertension, drinking, smoking, and physical exercise between Group A+C and Group A+B (all p > 0.05). The baseline characteristics of the 130 hypertensive patients are shown in Table 1.

TABLE 1.

Baseline characteristics of patients in Group A+C and Group A+B.

Item	Group A+C (n = 68)	Group A+B (n = 62)	t/X 2	p value
Age (year)	47.41±11.34	45.42±11.88	0.993	0.322
BMI (kg/m2)	25.62±2.60	26.21±2.74	−1.227	0.222
OSBP (mmHg)	152.60±9.60	150.23±10.31	1.717	0.205
ODBP (mmHg)	96.55±7.71	94.83±5.58	1.244	0.217
Smoking n (%)	22 (32.35)	27 (43.55)	1.782	0.182
Drinking n (%)	26 (38.24)	27 (43.55)	0.388	0.533
Physical exercise (%)	43 (63.24)	32 (51.61)	1.848	0.174
GLU (mmol/L)	5.42±1.02	5.24±0.77	0.974	0.333
Urea (mmol/L)	5.51±1.19	5.59±1.08	−0.398	0.691
eGFR	105.96±19.49	104.01±17.29	0.544	0.587
UA (µmol/L)	403.18±92.18	409.83±71.97	−0.408	0.684
TC (mmol/L)	3.99±1.04	4.29±0.92	−1.536	0.128
TG (mmol/L)	2.16±1.14	2.27±1.26	−0.463	0.644
LDL (mmol/L)	2.61±0.88	2.87±0.72	−1.639	0.104
HDL (mmol/L)	1.01±0.20	1.10±0.23	−2.020	0.066

Note: Group A+C: allisartan isoproxil tablets combined with amlodipine besylate tablets; Group A+B: allisartan isoproxil tablets combined with metoprolol succinate sustained‐release tablets. p < 0.05 indicates a statistically significant difference.

Abbreviations: BMI, body mass index; eGFR, estimated glomerular filtration rate; GLU, glucose; HDL, high‐density lipoprotein; LDL, low‐density lipoprotein; ODBP, office diastolic blood pressure; OSBP, office systolic blood pressure; TC, total cholesterol; TG, triglyceride; UA, uric acid.

3.3. Sexual Function

Compared with baseline, IIEF‐15 total score (ITS) of sexual function at 6 months significantly increased in Group A+C (49.55±20.21 vs. 53.93±17.92, p = 0.015), including IS (9.67±5.06 vs. 11.00±4.56, p = 0.003), OF (6.38±2.76 vs. 7.10 ±2.57, p = 0.021), and OS (9.53±3.01 vs. 10.12±2.57, p = 0.019). However, no significant changes were observed in EF and SD (both p > 0.05). In contrast, ITS decreased at 6 months in Group A+B (57.85±15.35 vs. 52.19±18.94, p = 0.008), in which EF (20.21±5.57 vs. 18.23±6.81, p = 0.005), IS (11.87±4.04 vs. 10.8±4.81, p = 0.048), SD (7.87±2.29 vs. 6.95±2.64, p = 0.003), and OS (10.51±2.06 vs. 9.43 ±2.77, p = 0.010) were lower than the baseline, but OF remained unchanged (p = 0.076). The intergroup comparison revealed significant differences in the change of the IIEF‐15 score before and after treatment (all p < 0.05). Sexual function outcomes for both groups are illustrated in Figure 2.

FIGURE 2.

Comparison of sexual function from baseline to 6 months within each group and intergroup differences in treatment‐induced changes. Group A+C: allisartan isoproxil tablets combined with amlodipine besylate tablets; Group A+B: allisartan isoproxil tablets combined with metoprolol succinate sustained‐release tablets. EF, erectile function; IS, intercourse satisfaction; ITS, IIEF‐15 total score; OF, orgasmic function; OS, overall satisfaction; SD, sexual desire.

3.4. BP Evaluation

3.4.1. OBP

After 6 months, both OSBP and ODBP significantly decreased from baseline in both groups (both p < 0.001). The decrease in ODBP was more significant in Group A+C than in Group A+B (Difference = −4.00 mmHg. 95% CI [−7.64, −0.36], p = 0.032). Changes in OBP and between‐group differences are shown in Figure 3.

FIGURE 3.

Changes in OBP from baseline to 6 months and between‐group differences in treatment‐induced changes. Group A+C: allisartan isoproxil tablets combined with amlodipine besylate tablets; Group A+B: allisartan isoproxil tablets combined with metoprolol succinate sustained‐release tablets. OBP, office blood pressure; ODBP, office diastolic blood pressure; OSBP, office systolic blood pressure.

3.4.2. ABPM

After 6 months, these ABPM parameters were all reduced from baseline in both groups (dSBP, dDBP, nSBP, nDBP, 24hSBP, 24hDBP, all p < 0.05). Notably, nBPF significantly increased after treatment in Group A+C (nSBPF: 5.24±6.18 vs. 8.62±6.76, p = 0.010; nDBPF: 5.60±5.69 vs. 9.88±7.05, p = 0.002). The nighttime–daytime BP fall ratio of SBP and DBP were 1.04 (0.45, 1.70) and 1.13 (0.38, 1.44), with median values greater than 1, indicating nBP fall was greater than dBP fall in Group A+C. However, the nighttime–daytime SBP and DPB fall ratio were 0.95 (0.16, 1.69) and 0.71 (−0.04, 1.47) respectively after treatment, with a median value less than 1, suggesting nBP fall was smaller than dBP fall in Group A+C.

Group A+C demonstrated superior in dDBP and 24hDBP compared to Group A+B (dDBP: difference = −5.47 mmHg, 95% CI [−10.05, −0.79], p = 0.023; 24hDBP: difference = −5.77 mmHg, 95% CI [−10.31, −1.24], p = 0.014). Additionally, the increase of nDBPF in Group A+C was more significant than that in Group A+B (difference = 4.99, 95%CI [0.04, 9.93], p = 0.048). ABPM changes and between‐group differences are illustrated in Figure 4.

FIGURE 4.

Changes in ABPM parameters from baseline to 6 months within each group and between‐group differences in treatment‐induced changes, 24hDBP, 24 hour average diastolic BP; 24hSBP, 24 hour average systolic BP; ABPM, ambulatory blood pressure monitoring; DBP, diastolic BP; dDBP, daytime average diastolic BP; dSBP, daytime average systolic BP; nDBP, nighttime average diastolic BP; nDBPF: nighttime diastolic BP fall; n/dBPFR, nighttime‐daytime BP fall ratio; nSBP, nighttime average systolic BP; nSBPF, nighttime systolic BP fall; SBP, systolic BP.

4. Discussion

Our findings provide novel evidence that the antihypertensive regimen of allisartan isoproxil combined with amlodipine besylate tablets conferred benefits in improving sexual function in male hypertensive patients. This advantage observed across multiple domains of the IIEF‐15, including the total IIEF‐15 score, IS, OF, and OS. Importantly, both allisartan isoproxil‐based antihypertensive regimens could effectively reduce BP. However, allisartan isoproxil combined with amlodipine besylate tablets was more advantageous in lowering DBP and nBP fall, and elevating nDBPF.

Sexual dysfunction is highly prevalent in male hypertensive patients and significantly affects quality of life, while antihypertensive drugs may also have an impact on sexual function [5, 17]. It was found in our study that Group A+C improved the total IIEF‐15 score, IS, OF, and OS, while SD and EF scores remained unchanged significantly. By contrast, the total IIEF‐15 score, EF, IS, SD, and OS reduced in Group A+B, but OF remained unchanged significantly. The mechanisms underlying the benefits observed in Group A+C may be multifactorial. Allisartan isoproxil increases NO, reduces ET, baPWV, and EMPs to improve endothelial dysfunction and arterial stiffness, reduces the levels of inflammatory factors TNF‐a and IL‐6 [18, 19], and regulates voltage‐gated potassium channels to improve vascular remodeling [20]. In addition, amlodipine besylate improves blood perfusion in the reproductive system through vasodilating blood vessels by blocking the calcium channels on the vascular smooth muscle cells. Together, these actions may explain the improvements in certain sexual function parameters. However, EF did not improve. This may be due to the fact that erection is a complex physiological process involving neural‐vascular‐endocrine synergism, which requires the normal operation of various links such as neural regulation, penile artery dilation, relaxation of corpus cavernosum smooth muscle, increased blood flow in the corpus cavernosum, and venous occlusion, especially the release of NO and the synthesis of cyclic guanosine monophosphate (cGMP). Although Group A+C increased NO levels, it did not significantly enhance cGMP production, which is precisely the therapeutic target of PDE5 inhibitors [21]. Conversely, the declines in sexual function observed in Group A+B may be attributable to the metoprolol succinate extended‐release tablets’ pharmacological effects. By blocking β‐receptors, suppressing over‐activated sympathetic activity, inhibiting myocardial contractility, slowing down the heart rate, and decreasing cardiac output, leading to reduced blood perfusion to the reproductive system. In addition, by lowering NO bioavailability, affecting the vascular endothelium, and inhibiting β‐receptor‐mediated peripheral vascular dilation, all of which weaken the ability of blood to flow into the reproductive system, resulting in insufficient blood supply and dysfunction of the reproductive system [22]. There has been controversy over the effects of beta‐blockers on sexual function, and there are no high‐quality randomized controlled trials (RCTs) to explore the effects of different types of beta‐blockers on sexual function [23, 24]. A previous study [14] reported that after 48 weeks of treatment with felodipine combined with irbesartan or metoprolol succinate extended‐release tablets, SD was elevated in the felodipine combined with irbesartan group (p < 0.05), while it remained unchanged significantly in patients treated with felodipine combined with metoprolol succinate extended‐release tablets. Another study using amlodipine combined with metoprolol tartrate or valsartan for 1 year in hypertensive men showed that the EF score was increased in patients using amlodipine combined with valsartan compared to baseline, while it was decreased in those using amlodipine combined with metoprolol tartrate [25]. Other studies used amlodipine besylate tablets combined with irbesartan or metoprolol succinate sustained‐release tablets in young and middle‐aged hypertensive men for 6 months, finding that both EF and SD were increased in patients using amlodipine besylate tablets combined with irbesartan, while EF, IS, OF, and SD remained unchanged significantly in patients using amlodipine besylate tablets combined with metoprolol succinate sustained‐release tablets [16]. Most prior research on antihypertensive drugs has been focused primarily on antihypertensive efficacy, with limited attention to sexual function as a clinical endpoint. This has resulted in fewer RCTs of the effects of either single or combination antihypertensive therapy on sexual function. In the future, there is an urgent need for multicenter, high‐quality RCTs to assess the effects of combination antihypertensive therapy on sexual function and to provide an evidence‐based rationale for clinical medication decisions for male hypertensive patients.

To achieve the target BP levels, combination antihypertensive therapy is required in clinical practice. Current guidelines also recommend the combination of two antihypertensive drugs as the initial therapy. What is more, it not only enhances BP control but also reduces the risk of cardiovascular events and stroke [26, 27]. Our study demonstrated that both Group A+C and Group A+B were effective in lowering BP, the former had certain advantages in lowering DBP and nBP fall, and elevating nDBPF. Recent RCTs have confirmed the efficacy of ARB‐based combination therapies in hypertension management. Sun's team conducted a 44‐center, open‐label RCT, demonstrating that allisartan isoproxil combined with either amlodipine besylate tablets or indapamide sustained‐release tablets achieved comparable reductions in SBP/DBP (14.03/8.30 mmHg vs. 14.41/8.20 mmHg) [12]. This also proved that the combined antihypertensive regimen based on allisartan isoproxil can effectively control BP. Similarly, the COLM study in Japan found that olmesartan combined with CCBs or diuretics achieved comparable reductions in the mean SBP/DBP (24.90/13.70 mmHg vs. 24.40/13.80 mmHg). However, olmesartan combined with CCBs has certain advantages in terms of safety and tolerability [28]. Nocturnal hypertension is a stronger predictor of target organ damage, adverse cardiovascular events, and cerebrovascular disease than dBP [1, 3, 29], so these findings have important clinical implications. Our study is the first to demonstrate that nighttime–daytime BP fall ratio > 1, suggesting that it is more advantageous for lowering nBP, which is of significant clinical value. A recent meta‐analysis exploring the efficacy of ARBs in reducing nBP confirmed that allisartan isoproxil reduced nBP more significantly and improved the circadian pattern of BP compared with dBP [30], which is broadly consistent with our study. In conclusion, our results support allisartan isoproxil combined with amlodipine as an effective initial regimen, especially in nBP management. It is necessary to conduct multi‐center clinical trials  on initial  combinatioan therapy using small dose or half‐dose of drugs for antihypertensive treatment in the future.

Not only does elevated nBP significantly increase the risk of target organ damage and adverse cardiovascular events but it is also associated with a higher incidence of ED [1]. Nocturnal hypertension is characterized by increased sympathetic and decreased parasympathetic activity at night. In the state of non‐sexual arousal, the sympathetic nerve maintains the contraction of the cavernous smooth muscle by releasing norepinephrine, which restricts the entry of blood into the penis, while the parasympathetic nerve promotes the relaxation of the cavernous smooth muscle by releasing NO, which facilitates penile perfusion.

Prolonged hyperactivity of the sympathetic and hypoactivity of the parasympathetic will lead to penile vasoconstriction and hypoperfusion, causing sexual dysfunction due to circulation disorders [31]. Allisartan isoproxil inhibits the renin–angiotensin–aldosterone system by blocking AT1R, reduces angiotensin II‐induced norepinephrine release, increases the release of NO and prostacyclin, reduces endothelial proliferation and vasoconstrictor factors release, improves vascular endothelial function, vasodilatation and perfusion, reduces vascular inflammation and stiffness, dilates small peripheral arteries, and reduces peripheral vascular resistance, thereby reducing BP and improving sexual function [21]. Amlodipine besylate dilates blood vessels and lowers BP by blocking calcium channels on vascular smooth muscle cells, and can improve nocturnal and early morning BP and BP variability [3]. Allisartan isoproxil combined with amlodipine besylate tablets improves ITS, IS, including OF, and OS in hypertensive patients. These benefits may be closely associated with the synergistic reduction of nBP and offset the side effects of the two drugs.

This study has several limitations. First, this is a single‐center clinical study with a relatively small sample size. Due to the impact of the COVID‐19 pandemic, patient enrollment was not continuous, and there is no double‐blind process in the trial process. Second, the treatment duration and follow‐up were relatively short. Third, sexual function was assessed mainly with the subjective IIEF‐15 questionnaire and lacked more objective measures. Despite these limitations, our findings suggest that allisartan isoproxil combined with amlodipine besylate tablets not only effectively lowers DBP and nBP but also improves certain aspects of sexual function in male hypertensive patients. These results highlight the potential clinical value of selecting antihypertensive therapies that simultaneously achieve optimal BP control and improve quality of life, particularly in relation to sexual health—a concern often overlooked in the management of hypertension.

5. Conclusion

Allisartan isoproxil combined with amlodipine besylate tablets improved sexual function in terms of the total IIEF‐15 score, IS, OF, and OS in male hypertensive patients, but did not improve EF or SD. Both allisartan isoproxil‐based combined antihypertensive regimens can effectively lower BP, but allisartan isoproxil combined with amlodipine besylate tablets is superior to allisartan isoproxil combined with metoprolol succinate sustained‐release tablets in reducing DBP and nBP.

Author Contributions

Mingming Wang: participated in the experimental process, follow‐up patients, data entry, data analysis, and wrote the manuscript. Jianshu Chen and Miao Miao Qi: participated in the experimental process and manuscript revision. Runmin Sun, Zhangyou Long, Quanbin Su, Yanhong Mou, and Hengxia Liu: helped follow‐up patients, data entry. Qiang Wu and Xiaowei Zhang: provided revising suggestions. Jing Yu: presided over the study design, participated in the experimental process, and manuscript revision.

Consent

Informed consent was obtained from each participant.

Conflicts of Interest

The authors declare no conflicts of interest.

Wang M., Chen J., Qi M., et al. “Effects of Two Allisartan Isoproxil‐Based Antihypertensive Therapies on Sexual Function and Blood Pressure in Male Hypertensive Patients: A Single‐Center, Open‐Label, and Randomized Controlled Trial.” The Journal of Clinical Hypertension 27, no. 9 (2025): e70145. 10.1111/jch.70145

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.