Letters to the Editor: Sleep Apnea, SPG Blocks for Migraines, Pancreatic Pain, CDC Guidelines
Sleep Apnea and Testosterone
A recent Letter to the Editor reminded me of my appreciation for Dr. Tennant’s work to make neurohormonal supplementation or replacement credible, as well as putting it in perspective as a component of the pain practice.
For over 3 decades, I have worked to assemble treatment teams for chronic pain or dysfunction. During this period, I have included testosterone and human chorionic gonadotropin (hCG) in my protocols, and routinely include testosterone in prolotherapy blends. I am writing, though, to suggest that sleep disordered breathing (SDB or sleep apnea) should also be considered as a contraindication to testosterone replacement therapy (TRT).
I believe that research will find that chronic TRT worsens SDB and may be a significant factor in the relationship between TRT and heart disease or stroke. I feel that periods of TRT or hCG can be helpful in combination with other therapies and life-style changes. I am hoping that research confirming the benefits and outlining the risks (and modifiers) for TRT can be forthcoming before its availability is curtailed.
Darick Nordstrom, DDS
Dear Dr. Nordstrom,
Your experience with TRT is well received. Now that you mention it, I think I’ve made the same observations without connecting the dots.
The co-occurrence of sleep disorders and pain is well known. According to the literature, sleep and fatigue symptoms have surpassed pain as the most prominent complaints in fibromyalgia patients, for example.1 It is also now recognized that sleep and pain are bidirectional, meaning poor sleep can predict chronic pain, and poor pain management contributes to sleep problems.2-4 Conversely, good sleep appears to improve the long-term prognosis of individuals with chronic pain conditions.
Therefore, it is not uncommon to conduct a sleep history when taking a medical history of a patient with pain. If sleep apnea is suspected, then early diagnosis and management are key to improved pain and sleep. Also known, but maybe not as recognized, is the role medications play in disrupting sleep. A growing body of research has repeatedly demonstrated that opioids disrupt sleep architecture and inhibit REM sleep.5,6
Beyond its role in sexual performance, testosterone plays a much wider and more critical role in pain management. Testosterone enhances analgesia, healing, and the immune response. It also is critical for prevention of osteoporosis, depression, and immobility. Without adequate serum testosterone levels, pain patients may complain not only of weakness, fatigue, depression, and loss of libido, but also poor pain control and hyperalgesia.
Thanks for sharing as your tip may be lifesaving to someone with SDB.
Forest Tennant, MD, DrPH
Exploration of hormone replacement therapy for patients experiencing chronic pain has been increasing in popularity over the last few years. It is well established that long-term opioid therapy can influence androgen deficiency. Endogenous testosterone rises and falls in a circadian fashion and varying levels are affected by the onset of rapid eye movement (REM) sleep.7 Once peak level is reached, it is sustained until morning and then decreases during the day.
Diminished REM sleep is found to correlate with decreased testosterone levels.7 And, a previous theory hypothesized that low testosterone levels may correlate with obstructive sleep apnea (OSA) due to decreased time spent in REM sleep. Correcting OSA with continuous positive airway pressure (CPAP) could at least theoretically increase testosterone levels; however, a meta-analysis performed by Zhang et al found no change in serum testosterone following CPAP intervention.7,8
Historically, OSA has been considered a contraindication to initiating testosterone replacement therapy (TRT), and in fact, the 2010 Endocrinology guidelines recommend against use in patients with OSA.9 The guidelines, however, admit this to be a recommendation with little supporting evidence and in fact recent research has given reason to re-examine.9-12
In 2003, Liu et al found short term TRT (3 weeks) to reduce sleep and worsen breathing; however, no anatomical changes were seen in this short duration.10 More recently, a randomized control trial performed by Hoyos et al examined the effects of long-term testosterone replacement therapy on OSA in 67 obese men.11 They found at 7 weeks of therapy a mild worsening of oxygen desaturation index and nocturnal hypoxemia compared to placebo; however, at 18 weeks of therapy this resolved.11 A subset of this study examined 21 men in an attempt to determine a mechanism for this change.12 The study hypothesized that the temporary effects might have been due to changes in chemoreflexes; however, the group instead found a correlation with hyperoxic ventilatory recruitment threshold and both serum testosterone and oxygen saturations.12 Certainly this evidence does not represent a green light for initiation of TRT in individuals with OSA but rather highlights the need for additional trials examining long-term therapy with an update to the current guidelines.
Erica Wegrzyn, BA, BS, PharmD
PGY1, Pharmacy Resident
MaineGeneral Medical Center
Jeffrey Fudin, BS, PharmD, FCCP, FASHP
CEO, Remitigate LLC
Director, Pain and Palliative Care Residency at Stratton VA Medical Center in Albany NY
Adjunct Associate Professor, Western New England University College of Pharmacy in Springfield MA
SPG Blocks for Migraines
In the recent article on sphenopalatine ganglion (SPG) blocks for migraines, there was an error in the parasympathetic pathways (Figure 1).13 It is the lacrimal nucleus that sends fibers through this ganglion. The superior salivatory nucleus sends its fibers through the submandibular (submaxillary) ganglion.
Could this block have any benefit in treating spinal headaches, as sometimes the triptans do?
G. Chudolij, MD
Dear Dr. Chudolij,
It is indeed correct that it is the lacrimal nucleus that sends fibers through the SPG. Most resources don’t differentiate the lacrimal nucleus from the salutatory nucleus, but if you look further, it is specifically the lacrimal nucleus that sends parasympathetics that end in the sphenopalatine ganglion. This is a relatively new technique being used in clinical practice, and as far as we know there is no literature indicating its use or effectiveness in spinal headaches, and we have not tried SPG blocks for spinal headaches. For refractory spinal headaches that don’t respond to usual treatment of hydration, caffeine, and blood patches, it is definitely worth trying the SPG block, which is a safe and simple procedure.