The reproductive health indices and sex hormone levels in middle-aged and elderly Chinese men

Abstract

Objective: The aim of this study was to analyze the age-related recession trajectory of reproductive health indices in middle-aged and elderly Chinese men.

Methods: A population-based cross-sectional study was conducted in Jiashan County, Zhejiang in 2012. Healthy men between 40 and 80 years of age were considered eligible for the study. Physical examination and the sex hormones were measured. The subjects were assessed based on the 5-item version of the International Index of Erectile Function (IIEF-5) for Erectile Dysfunction (ED), and Aging Males’ Symptoms (AMS) scale for Symptomatic Late-Onset Hypogonadism (SLOH).

Results: TG showed a decrease at age 60 years. Testis volume and TT did not show significant difference among the four age groups; cFT began to decrease at age 50 years and Bio-T decreased faster at age 50 years. SHBG and LH increased faster at age 50 and 70 years, respectively. IIEF5 score decrease faster at age 60 years. AMS scores increased faster at age 70 years. With the increase in age, the symptoms of ED and SLOH became severer.

Conclusion: Different indices on reproductive health of men showed turning points at different ages. At first, androgenic sex hormones decreased faster, and then erectile dysfunction got severer, and the last overall male syndromes declined.

• Androgenic sex hormone
• aging
• erectile dysfunction
• reproductive health
• trajectory

Introduction

In developing China, hectic lifestyle and heavy economic burden on individuals are inducing more health problems and premature aging on middle-aged people. Additionally, the number and proportion of older people in the Chinese population are growing rapidly. Aging causes severe public health issues. Furthermore, reproductive health is closely associated with overall wellness [1–3]. However, reproductive health research in China mainly focuses on younger child-bearing-age persons, infertile couples, or patients with reproductive system diseases. Health conditions of ordinary men are widely neglected after they father children. Limited information is available concerning the general and sexual health status of aging males, let alone males in rural area [4,5]. It is imperative to make a comprehensive assessment of reproductive health of middle-aged and elderly Chinese men, especially during the critical period of implementation of the universal two-child policy.

A cross-sectional study was performed in men aged 40–80 years old in east China county, through widely accepted scales about aging and reproductive health, as well as serum sex hormone profile. Our intention is to analyze the age-related recession trajectory of reproductive health indices in middle-aged and elderly Chinese men.

Materials and methods

Subjects

With the approval of the Institutional Ethical Review Committee of the First People’s Hospital of Jiashan County, Zhejiang province, the study was performed in communities of Jiashan County in 2012. All local men of 40–80 years of age were considered eligible for the study, excluding those: (1) having history of psychotic, cognitive disorders; (2) taking hormones, antiandrogen, or psychotropic agents; (3) had undergone pelvic surgical therapy. The research was performed according to the Declaration of Helsinki.

Investigation and physical examination

After obtaining written informed consent, uniformly trained investigators collected the information by face-to-face interview using uniform questionnaires about demographic information, as well as an abridged, 5-item version of International Index of Erectile Function (IIEF-5) and Aging Males’ Symptoms (AMS) scale [6–9].

The subjects were assessed based on the IIEF-5 for erectile dysfunction (ED), and AMS scale for Symptomatic Late-Onset Hypogonadism (SLOH). The IIEF-5 includes five questions and each scored on a rating scale of 1–5, for an overall score of 5–25. The severity of ED according to the IIEF-5 score was classified into five categories as severe (7 or less), moderate (8–11), mild to moderate (12–16), mild (17–21) or no ED (22–25). The AMS scale consists of 17 items and each item has a response with 5 degrees of severity (1–5 points).Based on AMS total score, ranging from 17 to 85, the subjects were classified as severe (50–85), moderate (37–49), mild (27–36), or no SLOH (17–26).

Body weight, height, waist circumference, blood pressure and testis volume were measured.

Laboratory measurement

All blood samples were drawn between 8:00 a.m. and 10:00 a.m. from overnight-fasting males to minimize the effects of diurnal variation. Serum levels of biochemical indices and sex hormone, including albumin (ALB), glucose (GLU), total cholesterol (TCHOL), triglyceride (TG), total testosterone (TT), sex hormone-binding globulin (SHBG) and luteinizing hormone (LH), were measured using chemical or luminescent methods (instruments and test agents were manufactured by Beckmann Co. of Bremen, Germany. The intra- and inter-assay variation coefficients were less than 8.5%. Serum level of calculated free testosterone (cFT) and bioavailable testosterone (Bio-T) was calculated from known values of TT, SHBG and serum albumin [10].

Statistical analysis

Data analyzes were performed with SAS9.1.3 package (SAS Institute, Cary, NC) and Stata 11 (Stata Corporation, College Station, TX).

Analysis of variance (ANOVA) was applied for testing overall difference. If significant difference was found, then the Student’s-Newman-Keuls method was applied for multiple comparisons of the means of indices in different age groups.

Locally weighted regression scatter plot smoothing fitting (LOWESS) was applied to explore possible curve correlation. The LOWESS method is a more refined nonparametric method than band regression. It obtains the smoothed Y value at a given X by fitting a linear regression to the data in the neighborhood of the X value and then using the fitted value at A as the smoothed value [11]. Based on the results of multiple comparisons, the LOWESS curve and statistical parameters of general linear regression, we selected appropriate regressions for the relationships between male reproductive health and age [12].

Chi-square tests were applied to analyze the differences of ED and SLOH among different age groups.

Results

A total of 969 men were admitted to the study. The age ranged between 40 and 80, with a mean of 56.4 ± 9.1 years.

SBP, DBP, PP and TCHOL did not show significant difference among 40–50, 51–60, 61–70, 71–80 age groups. BMI and waist circumference of the 71–80 age group were lower than other age groups, GLU was higher. TG showed a decrease at age 60 years (Table 1).

Table 1. Compare means of overall health indices in different age groups.

		BMI (kg/m^2)		Waist (cm)		SBP (mmHg)		DBP (mmHg)	PP (mmHg)	GLU (mmol/l)		TCHOL (mmol/l)	TG (mmol/l)
Age	N	Mean	SNK	Mean	SNK	Mean	SNK	Mean	Mean	Mean	SNK	Mean	Mean	SNK
Total	969	23.7		82.2		136.1		83.0	53.1	5.2		4.8	1.7
40–50	311	24.1	a	82.9	a	134.9	a	82.2	52	5.1	a	4.8	1.9	a
51–60	359	23.6	a	82	a	137	a	83.3	53.8	5.2	a	4.8	1.7	a
61–70	253	23.8	a	82.2	a	137.3	a	83.9	53.4	5.3	a	4.7	1.5	ab
71–80	46	22.5	b	80.2	b	134.9	a	80.6	54.3	5.7	b	4.8	1.2	b
F		5.19		2.85		3.05		1.63	1.75	3.1		0.4	5.4
P		0.02		0.04		0.03		0.18	0.15	0.03		0.73	<0.01

If significant difference was found by ANOVA analysis, Student’s-Newman-Kuels (SNK) method was applied for multiple comparisons. Different letters (i.e., a and b) mean there were significant difference between the two groups.

Testis volume did not show significant difference among different age groups. About scale scores, IIEF5 decreased with age and AMS scores increased with age. Different sexual hormone showed different changes with age. TT did not show significant difference among the four age groups, but cFT and Bio-T decreased with age. SHBG and LH increased with age (Table 2).

Table 2. Compare means of reproductive health in different age groups.

		Testis (cm^3)	IIEF5		AMS		TT (ng/ml)		cFT (ng/l)		Bio-T (ng/ml)		SHBG (nmol/l)		LH (IU/l)
Age	N	Mean	Mean	SNK	Mean	SNK	Mean	SNK	Mean	SNK	Mean	SNK	Mean	SNK	Mean	SNK
Total	969	30.0	17.2		23.7		4.1		67.9		1.8		43.3		5.9
40–50	311	31.1	20.7	a	20.6	a	3.9	a	74.6	a	2.0	a	33.3	a	4.6	a
51–60	359	29.4	17.8	b	23.6	b	4.1	a	67.6	b	1.8	b	42.7	b	5.7	b
61–70	253	29.5	13.9	c	26.1	c	4.2	a	62.4	c	1.6	c	51.3	c	6.9	c
71–80	46	30.4	7.3	d	32.2	d	4.2	a	54.7	d	1.4	d	63.8	d	11.2	d
F		1.90	123.0		70.0		3.1		41.6		56.7		63.5		62.0
P		0.13	<0.01		<0.01		0.03		<0.01		<0.01		<0.01		<0.01

If significant difference was found by ANOVA analysis, Student’s-Newman-Kuels (SNK) method was applied for multiple comparisons. Different letters (i.e., a and b) mean there were significant difference between the two groups.

LOWESS curves were very close to the fitted lines. LOWESS curves and linear regression model showed different indices have turning points differing with age. IIEF5 score decrease faster at age 60 years. AMS scores increased faster at age 70 years. CFT began to decrease at age 50 years, and Bio-T decreased faster at age 50 years. SHBG and LH increased faster at age 50 and 70 years, respectively (Figure 1).

Figure 1. Scatter plot and regression line. (dotted line: lowess curve solid line: fitted line).

As the age increased, the symptoms of ED and SLOH became severer, especially of ED (Table 3).

Table 3. The severity of symptoms in different age group.

		ED (%)					SLOH (%)
	N	None	Mild	Mild to moderate	Moderate	Severe	None	Mild	Moderate	Severe
Total	960	24.6	38.3	22.9	5.9	8.2	77.2	16.8	5.6	0.4
40–49	311	42.9	45.8	8.8	1.3	1.3	90.3	8.4	1.0	0.3
50–59	359	23.4	42.5	25.9	4.0	4.2	79.5	16.8	3.4	0.3
60–69	253	7.9	27.3	37.9	12.7	14.2	65.6	24.5	9.5	0.4
70–80	46	2.3	15.9	11.4	15.9	54.5	34.8	30.4	32.6	2.2
P*		<0.01					<0.01

*Non-zero correlation.

Discussion

On the whole, except 71–80 age group, general physical examination indices, such as BMI, blood pressure, glucose and lipid, did not show significant changes with aging. However, except testis volume and TT, reproductive health indices, such as IIEF5, AMS and androgenic sex hormone levels, showed significant decrease with aging. Different indices have different turning points of age. The unbound testosterone (cFT and Bio-T), erectile function and AMS score decreased faster at age 50, 60 and 70 years, respectively.

In our study, age correlated only with cFT and Bio-T, but not with TT. This is contrast to some previous reports [13–15], but a few studies also supported TT did not decrease with age [16,17]. In the Massachusetts Male Aging Study (MMAS), FT was found to be more predictive than TT [13]. SHBG and LH increased with age, especially after age 50 and 70 years, respectively. The correlations were similar to MMAS and Müezzinoğu’s results [18].

It has been widely proved that erectile dysfunction severity was closely associated with age [4,19–21]. In the current study, each additional year of increase in age caused a decrease in the IIEF-5 score of 0.291 (age range 40–60 years) or 0.581 (age range 60–80 years). It is similar to Kratzik’s study with a decrease of 0.195 (age range 45–60 years) [22].

The AMS scale has been translated into several languages (French, Polish, Nigerian, Japanese, Chinese, and so on) and most versions were widely accepted for good psychometric characteristics (reliability and validity) [23–27]. The positive correlation between age and AMS was similar to other studies [24,28,29], although some studies did not establish a relationship between aging and SLOH symptoms [21]. In the present study, the average AMS score and total incidence of SLOH were 23.7 and 22.8%, lower than the results in Hefei province, China (31.2 and 64.7%, aged over 45 years) or Japanese population [26,30].

One of the strengths of this study is that all data were collected by the same research team which promised extensive quality control. One physician took charge of one clinic mission to reduce variation. Large sample size provides robust parameter estimation and linear fit.

Zhejiang is a relatively rich province in China. All subjects are county habitants and their working and living pressures are lower than those in cities or metropolis. Therefore, results of this study are only valid for the more affluent rural people.

Considering the difference of education degree and understanding capacity on reproductive health knowledge, all questionnaires were investigated by trained researchers, although the scales were usually self-administered. Physicians were not familiar with subjects. Therefore, when subjects were asked sensitive questions, they would answer them factually and thought it was a good opportunity to consult physicians. The ED ratio in this study is low. It is hard to ascertain the underestimate proportion because men may be reluctant to discuss ED. Even by self-administered scale, it is still difficult to avoid undiagnosed instances. Furthermore, Only 38% of men reporting ED were concerned about it [31].

Recruitment bias may invalidate population studies of reproductive health because volunteers who participate in these studies may be healthier and may represent men with better fertility probability than the entire population of men from which they came.

In this article, results were based on cross-sectional data. We are following up these subjects and will analyze longitudinal data for age-related trajectory of male reproductive health. In addition, we only investigated the age-related trajectory on reproductive health, not considering other influence factors. In future manuscripts, we are going to explore the effects of other environmental factors on reproductive health, the complex correlation among sex hormones, sexual function and aging. When we analyze the relationship among sex hormone levels, physical status and related scale scores, we may need to stratify age to obtain more precise results.

In conclusion, reproductive health of men aged over 40 years decreased gradually. Different indices showed turning points that differ with age. Firstly, androgenic sex hormones decreased faster, and then erectile dysfunction became severer, lastly overall male syndromes declined.

Declaration of interest

The project was supported by National Science and Technology Basic Work Program [2013FY110500].