By: Alexa Schryver
Director’s Note: Men’s Health Week begins today, so we are featuring research that assessed the relationship between male fertility and overall health. The study and its findings are summarized below by Alexa Schryver, a former FACTS elective participant. The study[1] published by the American Society for Reproductive Medicine draws from prior research suggesting a relationship between abnormal semen analyses and cancer incidence, but it could be expanded to explore the use of male urinary hormones to assess fertility. Monitoring female urinary hormones is a common practice among users of symptoms-hormonal fertility awareness-based methods (FABMs), such as the Marquette Model. Given the correlation noted in the study between decreased testosterone and increased follicle-stimulating hormone with poor reproductive function, Schryver ponders whether men could also monitor these hormones to gain insight into their reproductive and overall health.
Introduction
Current research focuses on the quality of the menstrual cycle as a reflection of reproductive and overall health in female patients. When working with patients suffering from infertility, female patients are often instructed to track their menstrual cycle to give insight into their fertility health. However, men rarely have such clear, observable signs as clues to their reproductive health. Previous research indicates an abnormal semen analysis coincides with a higher incidence of several types of cancer, including testicular, colorectal, and prostate cancer.[2] [3] [4] The 2015 study[1] summarized below sought to investigate a correlation between fertility status and general health in male patients.
“Previous research indicates an abnormal semen analysis coincides with a higher incidence of several types of cancer, including testicular, colorectal, and prostate cancer.”
Methodology
The study by Ventimiglia et al utilized a cross-sectional survey design to assess a cohort of 2,100 white European men from 2005 to 2014. The patients met the following criteria: minimum 18 years of age and a diagnosis of either male factor infertility or mixed factor infertility. Assessments were made through self-reported medical history of age and comorbidities, including neoplasms, urogenital and systemic infections, autoimmune diseases, endocrinopathies and metabolic disorders, chronic kidney disease, and liver diseases. The Charlson Comorbidity Index (CCI) was used to score comorbidities, which were categorized as 0, 1, or more than 2.
Body mass index (BMI) was measured for each patient, and testicular volume was calculated using a Prader orchidometer. Two semen analyses were assessed for each patient, with both showing below-standard values based on WHO criteria. Venous blood samples were also drawn from each patient after an overnight fast and between the hours of 7 AM and 11 AM. The following measurements were taken from the venous blood samples: fasting glucose, total cholesterol, high-density lipoprotein C, triglyceride levels, follicle-stimulating hormone (FSH), luteinizing hormone, prolactin, thyroid-stimulating hormone, 17 beta-estradiol, inhibin B, anti-müllerian hormone, total testosterone, and sex hormone-binding globulin.
The data were presented as a mean, and the statistical significance of differences in mean was tested with the one-way ANOVA; the proportion was tested with the Pearson chi-squared test. The association between clinical predictors (age, BMI, length of infertility, and sperm parameters) and continuously coded CCI were tested using univariable and multivariable linear regression analyses. Additionally, the association between the clinical predictors and the presence of comorbidities was tested with logistic regression.
Results
Comorbidities split the patient population into the following groups: 0 comorbidities in 1,921 patients (91.5%), 1 comorbidity in 102 patients (4.9%), and 2+ comorbidities in 77 patients (3.6%). Decreased general health status was associated with increases in age and FSH. Lower total testosterone and sperm concentration were associated with higher numbers of comorbidities. Oligozoospermia and nonobstructive azoospermia were observed at higher rates in patients with comorbidities versus patients without comorbidities. With regards to testicular volume, hormonal or seminal parameters, no differences were observed between groups. Finally, patients who had sperm concentrations lower than 45.6 million/mL had a 2.74-fold increased risk of having one or more comorbidities.
“Lower total testosterone and sperm concentration were associated with higher numbers of comorbidities.”
Discussion
The study findings align well with the topics of family planning and fertility awareness. While the FACTS elective and online CME course place an emphasis on women’s health when discussing fertility and family planning, this study demonstrated the overall status of male health has a bigger role to play than previously thought.
The study concluded that men with lower overall health status have lower sperm concentration, lower total testosterone levels, and higher FSH values, which translated to general dysfunction of the male reproductive system. Given these findings, it is possible similar recommendations made to female patients regarding their infertility may apply to male patients as well. These recommendations include dietary and lifestyle habit modifications as well as treatment of any medical conditions — a more holistic approach in the management of infertility. By starting conservatively and addressing lifestyle factors in both patients, this approach offers more engagement and team effort in the process of achieving pregnancy.
“Similar recommendations made to female patients regarding their infertility may apply to male patients as well, including dietary and lifestyle modifications as well as treatment of any medical conditions.”
As a woman’s menstrual cycle is a marker of overall health, this study points to male infertility as an indicator of general health in men. The study design included a large cohort and demonstrated clinical significance. Its novel results provide insight for the management of infertility.
The study also had several limitations. The population was strictly European men and restricted to non-interracial couples seen at one academic outpatient clinic. The patients were all hospital-based, which is subject to selection bias, and the medical history was self-reported. The study lacked a comparison with a cohort of same-race and age-matched fertile individuals, and had no data regarding potential molecular alterations in spermatogenesis. The comorbidities in the inclusion criteria are more common in older populations than in patients in their thirties and forties. Lastly, the study compared patients without comorbidities to patients with 1 or more comorbidity. This reduces validity, as a lack of comorbidities does not necessarily equate to good health status.
It is interesting to note that oligospermia and nonobstructive azoospermia were observed at higher rates in patients with comorbidities. This could be due to a common mechanism affecting sperm production, or perhaps the comorbidity disease process directly impacts male reproductive function. It is also noteworthy that no differences were found in testicular volume or hormonal/seminal parameters between each group, as some of the comorbidities, such as liver disease, are known to directly affect estrogen/testosterone.
A question elicited by this study is whether a male patient could use urinary hormones to assess and/or monitor fertility. Given that decreased testosterone and increased FSH correlate with poor reproductive function, could patients measure these hormones to gain insight into their overall health as well as their fertility status?
Future research should seek to expand the study population and investigate the effects of more common diseases affecting this demographic. Additionally, these parameters should be compared to patients without infertility, as well as patients without comorbidities who are in good health. Future studies should also assess the use of urinary hormone test strips for the purpose of tracking male fertility for family planning.
References
[1] Ventimiglia E, Capogrosso P, Boeri L, et al. Infertility as a proxy of general male health: results of a cross-sectional survey. Fertil Steril. 2015;104(1):48-55. doi:10.1016/j.fertnstert.2015.04.020.
[2] Ramen JD, Nobert CF, Goldstein M. Increased incidence of testicular cancer in men presenting with infertility and abnormal semen analysis. J Urol 2005; 174:1819–22.
[3] Walsh TJ, Schembri M, Turek PJ, Chan JM, Carroll PR, Smith JF, et al. Increased risk of high-grade prostate cancer among infertile men. Cancer 2010;116:2140–7.
[4] Eisenberg ML, Betts P, Herder D, Lamb DJ, Lipshultz LI. Increased risk of can- cer among azoospermic men. Fertil Steril 2013;100:681–5.
ABOUT THE AUTHOR
Alexa Schryver
Alexa Schryver is a fourth-year medical student at St Matthew’s University School of Medicine in Grand Cayman, Cayman Islands. She completed her undergraduate education in athletic therapy at Concordia University in Montreal, Canada. She plans to complete residency in family medicine and is interested in sports medicine and women’s health. She enrolled in the FACTS elective to learn a more comprehensive and holistic approach to reproductive healthcare for her future patients. Alexa understands the primary care physician is the first point of contact for many patients; she enrolled in this elective to be able to offer patients more options before referring to specialists.
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