Most testosterone in the circulation is bound to sex hormone-binding globulin (SHBG) or to albumin, with approximately 0.5%–3% present as free testosterone, the biologically active hormone. Under most circumstances, measuring total testosterone is adequate for diagnosing testosterone deficiency. Total testosterone, however, can provide inaccurate estimates of bioactive testosterone in situations where SHBG values are altered, including several that are common among patients with CKD. Specifically, SHBG concentration may be low in patients with obesity, diabetes, and nephrotic syndrome and may be high in older patients. The Endocrine Society suggests measuring free testosterone levels in some men where total testosterone concentrations are near the lower limit of normal but alterations of SHBG are suspected. 

Diagnosis 

The diagnosis of hypogonadism is usually based on at least 2 consecutive morning (when levels are highest) low serum testosterone levels in conjunction with clinical symptoms.3 Because serum testosterone concentrations decline with age, some argue that the reference range should be age-specific. For example, consider 2 studies that measure testosterone in young and elderly men. Bhasin et al. found the 2.5th percentile of total testosterone to be 348.3 ng/dL in a sample of young men compared with 184 ng/dL for a sample of elderly men studied by Yeap et al.5 Therefore, using the standard reference range could lead to over diagnosis in the elderly population if symptoms are not considered as part of the diagnosis. 

Symptoms 

The diagnosis of hypogonadism is challenging because the signs and symptoms are non-specific and can vary based on age and comorbidities. Common symptoms that should be clearly defined include decreased libido, or the lack of sexual desire, and erectile dysfunction, the inability to acquire or maintain an erection needed for sexual intercourse. Other relatively specific signs include gynecomastia, loss of body hair, shrinking of testes, low sperm count, low bone mineral density, and hot flushes. Less specific symptoms include decreased energy, motivation, self confidence, depressed mood, poor concentration and memory, sleep disturbances, anemia, reduced muscle mass and strength, increased body fat and body mass index, and decreased physical performance. Therefore, a thorough history and physical examination should be performed to assess for these signs and symptoms. 

Testosterone replacement 

Clinical observations have suggested that low testosterone levels may have several adverse consequences, but the effect of testosterone replacement remains unclear. Trials have been limited by small sample size, different inclusion criteria, and variable testosterone regimens. There are even fewer data for the CKD population, so extrapolation from the general population is often necessary. 

Sexual function

In the general population, a meta-analysis of 17 randomized controlled trials of testosterone replacement with 862 participants showed moderate improvements in libido with only a small effect on erectile dysfunction.6 In addition, 2 small studies that evaluated effects of testosterone on sexual function in ESRD patients found that most patients experienced improvement in but not normalization of sexual function.

Physical function

Although not specifically aimed at patients with hypogonadism, there have been a few trials evaluating the effects of androgen therapy on physical function in patients with ESRD. In 1 study, researchers showed that administration of nandrolone deconate, a synthetic testosterone derivative, improved physical performance and increased lean body mass.9 In addition, studies of testosterone replacement among elderly men have generally shown improvement in the lean body mass, strength and physical function.

Bone mineral density 

Studies of the effects of testosterone on outcomes related to bone mineral density in patients with CKD are also limited, but some data are available in the general elderly population. Although results of these studies are mixed, improvements are more pronounced for patients with lower pre-treatment testosterone levels. Given that the causes of bone disease in patients with CKD are multifactorial, with secondary hyperparathyroidism as a major underlying mechanism, it may not be reasonable to generalize from the general elderly population to the CKD population. 

Adverse effects

Treatment with testosterone has known side effects, which include acne, male pattern baldness, gynecomastia, as well as more serious side effects, such as worsening sleep apnea, adverse CV outcomes, and accelerated growth of prostate cancer. With regard to CV outcomes, in a meta-analysis of 51 clinical trials, testosterone treatment was not associated with higher CV risk.14 Other evidence has been more concerning, however. A randomized controlled trial evaluating testosterone treatment in elderly men with mobility limitations and chronic disease was halted due to adverse CV events in the testosterone group.

In addition, 2 retrospective studies showed a higher risk of myocardial infarction (MI) in patients treated with testosterone, although the absolute risks were low.16,17 These retrospective studies were limited by the lack of available data on total testosterone concentrations and the indications for, and doses of, testosterone treatment. As yet, the FDA has not concluded that testosterone therapy increases the risk of MI or mortality; however, it warns clinicians to be aware of the concerns while investigations are underway. 

Conclusion 

Given the possible risk, especially among CKD patients who are already at high risk of cardiovascular disease, low testosterone levels should not be routinely treated among patients with CKD. However, treatment can be considered on an individual basis in symptomatic patients with poor physical function, fracture risk, and documented low testosterone levels. Patients receiving testosterone replacement therapy should be reassessed frequently, and therapy should be discontinued if benefit is not observed after a 3- to 6-month trial.

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I.        February 2015 – Mississippi Certificate of Need Meeting

During the February 26, 2015 Certificate of Need meeting, Dr. Mary Currier, State Health Officer, concurred with the health and planning staff analysis and approved the following applications for Certificate of Need.

CON Review # ESRD-RC-1014-013 – RCG Mississippi, Inc. d/b/a RCG Louisville – Repair ESRD Facility Due to Natural Disaster and Expansion – Capital Expenditure: $1,483,261 – Location: Louisville, Winston County, Mississippi – Staff Recommendation: Approval

CON Review # HG-CO1014-014 – Vicksburg Healthcare, LLC d/b/a River Region  Health System – Cost Overrun to CON No. R-0871 (CON Review No.: HG-MOB-0913-012) – Construction  of  River  Region  Medical  Office  Building  –  Approved  Capital  Expenditure: $13,245,099 – Additional Capital Expenditure: $3,723,912 – Location: Vicksburg, Warren County, Mississippi – Staff Recommendation: Approval

The next Certificate of Need meeting is scheduled for March 26, 2015, at 11:00 a.m.

II.         Certificate of Need Program Report – Filings/Reports Since January 2015

1. Letters of Intent to Change Ownership

1. Beacham Memorial Hospital – Change of Ownership – Received February 12, 2015

1. Determinations of Reviewability

1. Southern Surgery Center, LLC – Transfer of Real Property Owned by Southern Development Resources, LLC – Received February 6, 2015
2. Biloxi HMA, LLC d/b/a Biloxi Regional Medical Center – Acquisition of Membership Interest in Compass Imaging, LLC – Received February 6, 2015
3. North Mississippi Medical Center – Replacement of Radiation Therapy Equipment – North Linear Accelerator – Received February 12, 2015
4. Ocean Springs Hospital – Ocean Springs Hospital Wound Care Renovation – Received February 12, 2015
5. Mississippi Urology Clinic, PLLC – Single Specialty Ambulatory Surgery Center Urology –Received February 12, 2015

1. Tippah County Health Services – Inpatient Distinct Part Geriatric Psychiatric Unit (Senior Care) Ripley, MS – Received February 12, 2015
2. Rehabilitation Center, LLC d/b/a Millcreek Classroom Addition – Received February 12, 2015
3. Boliver Medical Center – Cosmetics Upgrades and Minor Renovations for Bolivar Medical Center – Received February 12, 2015
4. Bienville Surgery Center, LLC – Orthopaedic Surgery – Received February 20, 2015
5. St. Dominic Jackson Memorial Hospital – Expansion of Hospital Pharmacy – Received February 20, 2015
6. Hattiesburg Clinic, PA d/b/a Columbia Dialysis Unit – Rebuild of Columbia Dialysis Unit Received February 25, 2015
7. RCG MS, Inc. d/b/a RCG of Greenwood – Expansion of a Home Therapy Program – Received February 26, 2015

1. Letters of Intent to Apply for CON

             None

1. Applications Received/Withdrawn

1. Neshoba County General Hospital – Amendment/Cost Overrun to CON # HG-MOB- 0614-009; R-0879 – Medical Office Building – Received February 5, 2015
2. Harrison County Properties, LLC – Cost Overrun to CON # NH-RLS-0110-001; R:0819 – Construction of  90 Nursing Home Beds in Harrison County, Mississippi  – Received February 9, 2015
3. Madison HMA, LLC  d/b/a Merit  Health  Madison  –  Construction  of  Medical Office Building – Received February 27, 2015

1. Applications Received for Extension/Renewal of an Expired CON

None

1. Additional Material Received in Response to Negative Staff Analysis

None

1.  CON Applications Deemed Complete

None

1. Six-Month Extension Requests Granted

None

1. Hearings Requested/Scheduled During the Course of Review

None

1. Request for Hearing on Denial of Six-Month Extension

CON  Review  #  ESRD-NIS-0905-041;  CON  #  R-0710  –  Healthcare  Engineers,  LLC  – Establishment of a six-station ESRD facility in Tallahatchie County – Capital expenditure: $254,085 – Requestor: Alliance Health Partners, LLC, d/b/a Tri-Lakes Medical Center - To Be Scheduled

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Iron-based phosphate binders are as effective as sevelamer for treating hyperphosphatemia and may be useful in managing anemia in dialysis patients, according to a recently published systemic review and meta-analysis.

A team led by Rong Wang, MD, of Shandong Provincial Hospital in Shandong, China, analyzed 8 randomized controlled trials of iron-based phosphate binders with a total of 2,018 dialysis patients. The binders were superior to placebo in decreasing serum phosphorus levels (mean decrease of 2.43 vs. 1.68 mg/dL), the investigators reported in Renal Failure (2015;37:7-15). Iron-based binders and sevelamer decreased serum phosphorus to a similar extent.

Compared with placebo, iron-based binders were associated with significantly higher serum iron and serum transferrin saturation and significantly lower serum total iron binding capacity.

The researchers concluded that “iron-based phosphate binders may represent a new treatment option for dialysis patients.”

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