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- Original Article -
Do reproductive hormones explain the association between
body mass index and semen quality?
Dan-Dan Qin1, 2, Wei
Yuan2, Wei-Jin Zhou2, Yuan-Qi
Cui3, Jun-Qing Wu2, Er-Sheng
Gao2
1School of Public Health, Fudan University, Shanghai 200433, China
2Shanghai Institute of Planned Parenthood Research, Shanghai 200032, China
3Commission of Population and Family Planning, Shanghai 200002, China
Abstract
Aim: To examine whether reproductive hormones play a role in the association between body mass index (BMI) and
semen quality. Methods: Semen quality and testosterone (T), luteinizing hormone (LH), follicle-stimulating hormone
(FSH) and estradiol (E2) were evaluated in 990 fertile males with age 38.9 ± 9.7 (mean ± SD) years recruited from the
Chinese general population in 2001 and 2002.
Results: Semen quality was reduced among underweight (BMI <
18.5) compared with normal (BMI 18.5_24.9) and overweight (BMI 25.0_29.9), but the associations were independent of
reproductive hormones. After adjustment for the potential confounders, underweight men had reductions in sperm
concentration (22.4 × 106/mL), total sperm count (52.9 ×
106) and percentage of normal sperm forms (6.9%)
compared with men with normal BMI. Being underweight may be a risk factor for low sperm concentration (OR:
4.68, 95% confidence intervals [CI]: 2.01_10.91). Otherwise, being overweight may be a protected
factor for low sperm concentration (OR: 0.25; 95% CI: 0.08_0.83) and low total sperm count (OR: 0.37, 95% CI:
0.15_0.87). Conclusion: Low BMI was associated with reduced semen quality. The associations between BMI and semen quality were found
statistically significant even after adjustment for reproductive hormones. Reproductive hormones cannot explain the
association between BMI and semen quality. (Asian J Androl 2007 Nov; 9: 827_834)
Keywords: semen quality; reproductive hormones; body mass index
Correspondence to: Dr Er-Sheng Gao, Shanghai Institute of Planned Parenthood Research, 2140 Xietu Road, Shanghai 200032, China.
Tel: +86-21-6404-6106 Fax: +86-21-6404-3701
E-mail: ersheng_gao@yahoo.com.cn
Received 2006-10-01 Accepted 2007-01-24
DOI: 10.1111/j.1745-7262.2007.00268.x
1 Introduction
Being underweight or overweight has adverse effects on reproduction. Even with assisted reproductive technology,
both morbidly obese and severely underweight women have a decreased chance of pregnancy. Weight may influence
fertility by affecting insulin resistance, androgen binding, and ovulatory function
[1]. Some epidemiological studies have investigated the relationships between semen quality and body mass index (BMI) in fertile men. High or low BMI
was associated with reduced semen quality [2_4].
Reproductive hormones are also associated with body mass by influencing both fat and muscle tissues, and cause
changes for body mass [5_9]. A hypothesis was reasonably proposed by some investigators as to whether
there was an intermediate role of reproductive hormones in the
association between BMI and semen quality. Despite
the vast published literature on male semen quality and
reproductive hormones and BMI [3_5, 10], no
stu-dies could be found in the literature that had comprehensively
examined to what extent reproductive endocrines explained the relationship between individual BMI and
semen parameters in humans. No study had satisfactorily
focused on the hormonal status such as luteinizing
hormone (LH), follicle stimulating hormone (FSH),
testosterone (T) and estradiol (E2) and the relationship between
BMI and semen quality of fertile males.
Thus the reproductive hormones and BMI of 990 male fertile subjects from five provinces in China were
examined. We studied whether reproductive hormones
could explain the association between BMI and semen
quality in fertile men among the Chinese general population.
2 Materials and methods
2.1 Study population
Nine hundred and ninety male volunteers aged 20_60
years were enrolled in the study from January 2001 to
December 2002. All subjects had lived in the localities for
at least 5 years and represent the general population for
South China and North China in five cities, including Hebei,
Shanxi, Guizhou, Zhejiang and Shandong provinces.
Half of the subjects were selected in urban areas, and the
rest in rural areas. Men who suffered from chronic
diseases such as diabetes, kidney disease, atherosclerosis,
vascular disease and hypertension were excluded from
the study. Subjects with genital diseases, heavy smoking
and regular alcohol consumption were also excluded.
The trained staff informed the subjects about the
study and obtained their informed consent. They
underwent physical examination in Maternal and Child Health
Care Centers in the five geographical areas.
2.2 Questionnaire
All subjects completed a questionnaire on the day of
the physical examination by face-to-face interview. The
questionnaire included information on their demographic
characters, period of abstinence and the diseases in
reproductive organs (previous or current genital diseases
such as cryptorchidism, inguinal hernia, varicocele,
epididymitis, gonorrhea, chlamydia, and operation for
torsion of the testis). The subjects were asked their
education level and the current health situation. Smoking
habits were reported as the average number of cigarettes
or pipes smoked per day. The total weekly alcohol
intake (number of drinks) was estimated by calculating
the beer, wine, and liquor intake.
2.3 Physical examinations
Physical examinations were performed by a trained
physician in each location. The weight of the subjects
was measured in kilograms using one weighing scale by
the doctors in each center. Height was measured in
centimeters without socks and shoes, with the subject's eyes
and ears on the same horizontal line. The BMI was
calculated as weight in kilograms divided by the squared
height in meters (kg/m2). The possible presence of a
varicocele, a hydrocele, the location of testis in scrotum,
and the consistency of the testis and epididymis were
also recorded.
2.4 Semen collection and analysis
Semen specimens were collected in a sterile plastic
container in a private room near the laboratory after a
period of 2 to 6 days of sexual abstinence. The duration
of sexual abstinence and season at semen collection were
recorded. All the semen samples were kept at 37ºC to
liquefy to make routine semen analysis according to the
World Health Organization guidelines [11]. The semen
smears were air-dried, stained and preserved, and the
same technician assessed all the smeared slides to
determine sperm morphology.
The following semen variables were used as outcome
variables: semen volume, sperm concentration, total sperm
count, percentage of motile spermatozoa
(percentage of sperm with rapid and linear progressive motility and
sluggish linear motility), and percentage of normal sperm
forms. Normal values for standard sperm parameters
were considered as sperm concentration ¡Ý 20 ×
106/mL, total sperm count ¡Ý 40 ×
106 and percentage of normal sperm forms
¡Ý 30%.
The laboratory had been under the external quality
assessment scheme for the andrology laboratory by the
trained staff. Weekly laboratory controls were performed
by examining the same semen samples blindly. The
variations of all semen parameters were less than 5%
throughout the study period.
2.5 Hormone analysis
All blood samples were collected from a cubital vein
into 10 mL vacuum tubes for serum collection for each
subject at 8:00_10:00 in the morning. After cooling at
room temperature, the tubes were centrifuged at 3 000 ×
g for 10 min. Blood samples were separated and frozen
immediately. After a maximum of 7 days in the refrigerator, sera were stored at _70ºC and kept
frozen until analysis. All analyses were performed by the
trained technician at the Obstetrics and Gynecology
Hospital of Medical Center, Fudan University (Shanghai,
China).
Serum concentrations of hormones (T, FSH, LH and
E2) were measured by radioimmunoassay (Kit
Coat-A-Count; Diagnostic Products Corporation, Los Angeles,
CA, USA). The lower limits of detection (LODs) for the
assays were 0.1 nmol/L, 0.2 IU/L, 0.2 IU/L, and 8.0
pmol/L, respectively. Inter- and intra-assay coefficients of
variation (CV) for both FSH and LH were 3% and 4.5%. The
intra- and inter-assay CV for T were 6% and 8%. The
intra- and inter-assay CV for E2 were 7.5% and 13%,
respectively.
2.6 Statistical analysis
Overall differences in sperm concentration, total
sperm count, percentages of morphologically normal and
motile spermatozoa and semen volume between BMI groups categorized into four BMI groups as `underweight'
(BMI < 18.5), `normal' (18.5_24.9), `overweight'
(25.0_29.9), and `obese' (BMI ¡Ý 30) based on World Health
Organization classification [12] were analyzed by ANOVA. Once significance was established, post hoc
tests (Tukey's or Bonferroni's) were performed to
make comparisons among different BMI groups. Multivariate
ANOVA and logistic regression were used to control for
potential confounders. Correlations between semen
parameters and BMI were tested by partial correlation
method.
The potential confounders included smoking
(yes/no), alcohol intake (> 1 alcohol drink per week, yes/no),
season of semen sampling (April_September/October_March), period of abstinence (less than 3 days or 4_5
days or 6 days later), and age (years, as a continuous
variable). Previous history of urogenital disorder (all
disorders were grouped into one binary variable).
Reproductive hormones were categorized as three groups
(subjects with normal reproductive hormones taken as a
reference) and entered as dummy variables in stepwise
(the laboratory's internal normal reference range: LH
[3.3_13.5 IU/L], FSH [4.4_20.2 IU/L], testosterone
[12.7_39.7 nmol/L], E2 [32.8_207.4 pmol/L]). The
characteristics of the study populations with respect to potential
confounders are shown in Table 1.
The risk of abnormal semen quality between
different BMI groups was estimated by their odds ratios. The
potential confounders were added to the model
step-by-step according to their effect on the risk estimate, but
were excluded stepwise only if they were not
statistically significant at a 10% level. Data analyses were
performed with an SAS 8.1e package (SAS Institute, Cary,
NC, USA).
3 Results
Characteristics of subjects were shown in Table 1.
Almost all participants (97.4%) reported no previous
history of urogenital disorders. The subjects had the
BMI of 23.2 ± 2.9 kg/m2 (mean ± SD) and a mean age
of 38.9 ± 9.7 years (mean ±SD). Forty-two subjects
(4.2%) were classified as underweight, 690 (69.8%)
as normal weight, 241 (24.3%) as overweight and 17
(1.7%) as obese. Mean ages ± SD in four BMI groups
were 37.3 ± 10.1 years, 38.4
± 9.9 years, 39.9 ± 9.9 years
and 39.0 ± 9.9 years. And their mean BMIs ± SD
were 17.7 ± 0.7
kg/m2, 22.2 ± 1.8
kg/m2, 26.6 ± 1.2
kg/m2 and 31.4 ± 1.6
kg/m2, respectively. The mean duration of
abstinence was 4.9 ± 1.6 days among all the subjects.
Mean ± SD of abstinence days in four BMI groups were
4.6 ± 1.4, 4.8 ± 1.3, 5.1 ± 2.3 and 4.8 ± 1.0, respectively.
Fifty-one percent of the subjects had their semen collected
in October_March and 49% in April_September. A weekly alcohol intake and regular smoking were
reported by 46.1% and 49.3%, respectively. The mean ±
SD of serum T, LH, FSH and E2 were 19.09 ± 7.75
nmol/L, 4.43 ± 1.08 IU/L, 5.02 ± 3.05 IU/L and 18.93 ± 6.59 pmol/L,
respectively. Only serum T and FSH were different
across BMI groups. Serum T of underweight men (26.37 ± 1.62 nmol/L) was the highest among all the
BMI groups, whereas FSH of obese men was the highest (7.38 ± 1.22 IU/L) (data not shown).
Sperm concentration, total sperm count and percent
of normal sperm forms of the underweight (BMI <
18.5) men were 45.2 × 106/mL, 117.8 ×
106 and 35.8%, respectively, which were lower than the normal men (BMI
18.5_24.9) and overweight men (BMI 25.0_29.9). The
percentage of motile sperm was 74.5%, which was higher
than those men with normal BMI and overweight men.
The semen volumes of different BMI groups were not
statistically significant (Table 2). After adjustment for
study centers, age, diseases in reproductive organs,
smoking, alcohol and period of abstinence, underweight
men had reductions in sperm concentration (22.4 ×
106/mL), total sperm count (52.9 ×
106/mL) and percentage of normal sperm forms (6.9%) compared with men with
normal BMI. Semen volume and the percentage of motile
spermatozoa were, however, not associated with a
reduced BMI. After adjustment for the above
cofounders together with reproductive hormones, underweight men
still had significant reductions in sperm concentration
(18.4 × 106/mL), total sperm count (46.7 ×
106/mL) and percentage of normal sperm forms (5.7%) compared with
men with normal BMI, although the reductions seemed
to be slightly smaller.
After controlling for no variable or the serum T, LH,
FSH, E2 or all four reproductive hormones, respectively,
partial correlation analyses showed that a significant
positive correlation between BMI and sperm concentration,
the total sperm count and percentage of spermatozoa of
normal morphology. A significant negative correlation
between BMI and percentage of motile sperm was found.
But the correlation between BMI and semen volume was
not found (Table 3).
Abnormal cases of semen quality in obese men (BMI
¡Ý 30.0) were too few to conduct separate analyses. In
the unadjusted model 1, underweight men (BMI < 18.5)
had a higher, but insignificant, risk of low sperm
concentration (OR: 1.87; 95% confidence intervals [CI]:
0.74_4.73), low total sperm count (OR: 1.70; 95% CI:
0.25_1.97), and low percentage of normal sperm forms
(OR: 1.91; 95% CI: 0.91_4.01). Overweight men (BMI
25.0_29.9) had a lower, but insignificant, risk of low
sperm concentration (OR: 0.45; 95% CI: 0.13_1.61), low
total sperm count (OR: 0.70; 95% CI: 0.27_1.80) and
low percentage of normal sperm forms (OR: 0.71, 95%
CI: 0.44_1.13). No association between BMI and low
percentage of normal sperm forms was found (Table 4).
Associations between BMI and abnormal semen quality after adjustment for study centers, age, diseases
in reproductive organs, smoking, alcohol and period of
abstinence are presented in model 2. The proportion of
abnormal semen quality as a function of BMI in the
underweight, overweight and obese groups tended to be
uniform compared with the normal BMI group. Being
underweight may have an increased risk of low sperm
concentration (OR: 4.68; 95% CI: 2.01_10.91). Otherwise, being overweight may have protected
factors for the low sperm concentration (OR: 0.25; 95%
CI: 0.08_0.83) and low total sperm count (OR: 0.37;
95% CI: 0.15_0.87) compared with men with normal BMI, respectively. Association between BMI and low
percentage of normal sperm forms was not found as yet
(Table 4).
Additional analyses were conducted to determine
whether the reproductive hormones were caused by a
specific source of abnormal semen quality or whether
they were consistent among those BMI from either low
or high. Among model 3, the same tendency for the
point ORs estimate were present after adjustment for
study centers, age, diseases in reproductive organs,
smoking, alcohol and period of abstinence and
reproductive hormones. The same tendency of ORs for the
associations between BMI and low sperm concentration
and low total sperm count was found, although the strength of associations differed. Being underweight may
have an increased risk of low sperm concentration (OR:
5.56; 95% CI: 2.36_13.12). Otherwise, being overweight
may have protected factors for low sperm concentration (OR: 0.20; 95% CI: 0.05_0.84) and low total sperm
count (OR: 0.25: 95% CI: 0.08_0.83) compared with men with normal BMI, respectively. No association
between BMI and low percentage of normal sperm forms
was found after adjustment for reproductive hormones
(Table 4).
4 Discussion
Slight changes of the associations between BMI and
semen quality were found when reproductive hormones
were taken into consideration, but most of the
associations remained significant after adjustment. Similar
results were reproduced when semen indices were
examined as either continuous variables or categorized as
abnormal. Even after adjustment for the T, LH, FSH,
E2 and all the reproductive hormones, BMI had a
statistically significant correlation with the semen quality.
The significant association between BMI and lower
sperm concentrations and total sperm counts has been
reported in previous studies, but none took reproductive
hormones into consideration in the association between
BMI and semen quality [2_5, 13_15]. The current study
indicated that the association between BMI and semen
quality was clearly more complex than could be accounted for simply by reproductive hormones. It has
also been suggested that high T was not a predictor of
semen quality [2], however, the mean serum FSH concentration was higher in obese men with slightly reduced
semen quantity. Thus, the finding of FSH
hypersecretion in the obese group suggests that there were other
factors resulting into reduced semen quality. In addition,
the concentration of FSH did not differ between the
underweight, normal and overweight groups. A word of
caution is warranted, however, as we collected only a
single blood sample, and this may have been insufficient
to reveal true changes because of marked fluctuations of
the reproductive hormones' concentration.
The significant correlation between BMI and sperm
concentration, total sperm count, percentage of motile
sperm and sperm with normal morphology was found even after adjustment for the reproductive hormones.
These findings were unlikely to explain the effect of the
reproductive hormones.
It is well known that the testicle is responsible for
both the production of sperm and the synthesis of
testosterone (T) in adult males. Control of both functions is
guided by the central nervous system in a classic
endocrine feedback loop with FSH and LH as the key
hormonal signals. LH acts on Leydig cells in the testicular
interstitium to promote the synthesis of T, while FSH
affects the Sertoli cells thereby facilitating
spermato-genesis. FSH and LH secretion from the anterior
pituitary is regulated by hormonal signals from both the
hypothalamus and the testes, including T,
E2, dihydrotes-tosterone (DHT) and inhibin B. It is clear that
reproductive hormones regulate the development of sperm in a
wide range of mechanisms [16]. It has also been
suggested that higher concentrations of T may be a facilitating
factor for spermatogenesis, and FSH could positively
influence the quality [17]. Indeed, a previous report
indicated that reproductive hormones can be predictors
for semen quality in couples without known reduced
fertility [18].
Further studies are needed to assess whether the
changes in an amplitude range of reproductive hormones
may be attributed to an intermediate effect on the
association between BMI and semen quality or to a masking
effect. Likewise, to what extent the differences between
various levels of the reproductive hormones can affect
the BMI or the semen quality should be further explored.
Our results with regard to hypersecretion of T and FSH
levels in underweight and obese males of general
population indicated that measurements of T and FSH may not
represent natural function.
In conclusion, the current study indicated that
semen quality was reduced among underweight men
compared with normal BMI, but the associations were
independent of reproductive hormones. It did not support
the hypothesis that reproductive hormones play an
intermediate or confounding role in the association between
BMI and semen quality. Potential confounding bias,
however, could not be ruled out completely. It remains
unknown how BMI plays a role in the changed semen quality. Clearly, these findings must be confirmed by
other studies. However, it seems reasonable to advise
underweight men to avoid being too thin, as it may cause
adverse semen quality.
Acknowledgment
This study was supported by the Science and
Technology Commission of Shanghai, China (No.
02DJ14053) and National Population and Family Planning
Commission of China (No. 9902).
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