Stellate Ganglion Blockade Provides Relief from Menopausal Hot Flashes: A Case Report Series ABSTRACT

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JOURNAL OF WOMEN S HEALTH Volume 14, Numer 8, 2005 Mary Ann Lieert, Inc. Stellate Ganglion Blockade Provides Relief from Menopausal Hot Flashes: A Case Report Series EUGENE LIPOV, M.D., 1 SERGEI LIPOV,
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JOURNAL OF WOMEN S HEALTH Volume 14, Numer 8, 2005 Mary Ann Lieert, Inc. Stellate Ganglion Blockade Provides Relief from Menopausal Hot Flashes: A Case Report Series EUGENE LIPOV, M.D., 1 SERGEI LIPOV, M.D., 2 and JAMIE T. STARK, Ph.D. 3 ABSTRACT Ojective: To investigate whether standard C6 stellate ganglion lockade (SGB) might provide relief from hot flashes associated with menopause. Methods: Six women were referred for severe menopausal hot flashes and elected to undergo standard SGB (5 ml 0.375% Marcaine, Aott Las, Aott Park, IL) to evaluate a novel intervention for hot flash relief. Hot flashes were assessed y self-reporting efore and after stellate ganglion lock. Results: Initial SGB (SGB1) was successful in all 6 sujects, as evidenced y a positive Horner s syndrome and anhydrosis. Successful SGB caused complete alleviation of hot flashes for times ranging from 2 to 5 weeks. Patients returned for follow-up SGB after mild hot flashes returned. A second SGB produced additional asymptomatic periods of relief ranging from 4 to 18 weeks. In each case, repeated lock provided hot flash relief equal to or greater than that of the initial lock. Two patients who sumitted for a third SGB reported 15 and 48 weeks of relief. Conclusion: Successful SGB appears to e related to relief of hot flashes. Repeat SGB results in efficacious multiple week relief of severe hot flashes associated with menopause. INTRODUCTION HOT FLASHES ARE THE MOST COMMON symptom associated with menopause and have een reported to occur in 68% 82% of naturally menopausal women. 1 Surgical menopause is associated with increased incidence and severity of hot flashes compared with natural menopause. 2 As reviewed y Freedman, 1 surgical menopause causes hot flash incidence as high as 90%. Hot flashes have een reported in 21%, 30%, and 36% of women during premenopause, menopause, and postmenopause, respectively. 2 Importantly, these results were reported in women not taking hormone therapy, for whom symptoms are likely to e minimal. Independent of etiology, hot flashes have een reported to occur daily in as many as 87% of symptomatic women, and over one third of these women reported more than 10 hot flashes per day. 3 Hot flashes have een reported to occur as early as 2 years prior to menopause, and 50% of women experience hot flashes for up to 5 years. In addition, a small suset of women experience hot flashes for the duration of their life (reviewed in ref. 4). Hot flashes are the most common reason women seek hormone therapy. 5 Although hormone therapy results in an 80% 90% reduction in the 1 Advanced Pain Centers, S.C., Westmont, Illinois. 2 Internamed, Elgin, Illinois. 3 Athletic and Therapeutic Institute, Romeoville, Illinois. Manuscript preparation was supported y the Athletic and Therapeutic Institute. 737 738 occurrence of hot flashes in symptomatic women, complications with hormone therapy include headache, nausea, water retention, premenstrual irritaility, and withdrawal vaginal leeding, all of which affect quality of life. 6 In fact, withdrawal leeding is the most common reason women discontinue hormone therapy. 7 Additionally, the fear of cancer has een reported to cause apprehension toward eginning hormone therapy and has also een listed as a major reason for discontinuing hormone therapy. 8 Also of note, hormone therapy use has decreased since the Women s Health Initiative (WHI) reported conflicting results aout its efficacy. 9 These factors have led women to seek out alternative, nonhormoneased therapies for hot flash relief. Recent reviews of nonhormonal treatments for hot flashes concluded that phytoestrogens and lack cohosh are oth ineffective in providing symptomatic relief and are potentially dangerous. 4,6,10,11 Other methods (including lifestyle intervention and vitamin E therapy) are only marginally more effective than placeo in relieving hot flashes. The most promising nonhormonal therapy, selective serotonin reuptake inhiitors (SSRIs), have een reported to reduce hot flash scores (reviewed in ref. 11), ut SSRIs appear to e much less effective than hormone therapy. These factors highlight the need for novel, nonhormone-ased therapies for hot flash relief. Hot flashes are marked y sweating in the face, head, neck, and chest and generally last 1 5 minutes. Symptomatically, hot flashes appear similar to hyperhidrosis, a condition for which sympathectomy has een used successfully as treatment. 12 Because hot flashes typically occur during a discrete time frame surrounding the menopausal period, sympathetic lock may provide a nonhormonal alternative for hot flash relief during the symptomatic period, without removal of any sympathetic ganglia. Thus, we hypothesized that a sympathetic lock at the level of the stellate ganglion would provide relief from severe hot flashes associated with menopause. MATERIALS AND METHODS LIPOV ET AL. Participants Six menopausal women (aged years) with severe hot flashes were included in this case study. Women were referred y their gynecologists for evaluation of stellate ganglion lock (SGB) as an intervention for hot flash relief. Participation in the study group was elective, and all women provided written consent. Women who were medically unstale, on hormone therapy, had a lood clotting disorder, or had an American Society of Anesthesiologists (ASA) physical status score of P3 or higher were excluded from the study (P1, no disease; P2, mild [one systemic disease]; P3, moderate disease [more than 1 systemic disease]; P4, severe disease; P5, life-threatening disease). Procedures Patients underwent a standard SGB performed on the anteriolateral aspect of the C6 vertera on the right side. Current indications for SGB include complex regional pain syndrome 1 or 2 of the upper extremities, atypical facial pain, and complex regional pain syndrome 1 or 2 of the chest. The use of SGB in the current study may e considered y some to e off-lael use of this approved technique; however, no information clarifying this issue could e located on the Food and Drug Administration (FDA) wesite. Therefore, the authors contend that SGB should e performed only y oard-certified anesthesiologists with visualization via fluoroscopy. Briefly, following local analgesia (2% lidocaine), 2 ml iohexol (180 mg/ml) (Omnipaque, Sanofi Winthrop, New York, NY) was injected to visualize the ganglion and confirm needle placement via radiography. Marcaine (5 ml of 0.375%) (Aott) was then injected into the stellate ganglion to produce a sympathetic lock. Efficacy of the SGB was confirmed y the presence of Horner s syndrome and anhidrosis (asence of facial sweat). Horner s syndrome consists of enophthalmos (sinking of the eyeall into its cavity), ptosis (droopy upper eyelid), swelling of the lower eyelid, miosis (anormal contraction of the pupil), and heterochromia (difference in eye color). All these signs signify lock of the sympathetic nervous system as it supplies the eye on the effected side of the head. SGB carries the risks of infection, leeding, seizures, and spinal cord trauma; however, all can e effectively minimized with the use of contrast dye and fluoroscopic guidance. Analysis of self-reporting Information aout frequency and severity of hot flashes efore and after SGB was otained SYMPATHETIC BLOCKADE RELIEVES HOT FLASHES 739 via consultation with the anesthesiologist (E.L.). Symptoms were self-monitored, and patients returned for additional SGB when hot flashes elevated past a level considered mild, as defined y the patient. Moderate to severe hot flashes were defined as 7 10 hot flashes per day that caused interruption of daily activities. All women in this study experienced more than 10 hot flashes per day. Four of six women reported two or more hot flashes during the night that interrupted sleep. Patients were called prior to sumission of this paper to confirm current relief status. The data contained in this paper are the result of an extended case study in 6 individuals and should e interpreted as such. RESULTS Stellate ganglion lock Patient information and the results of SGB are shown in Tale 1. Initial SGB (SGB1) was successful in all 6 patients, as evidenced y a positive Horner s syndrome and anhidrosis. Repeat SGB (SGB2) was successful in 5 of 6 patients. Patient 2 displayed a delayed Horner s syndrome and lack of anhidrosis following SGB2, indicating the lack of a successful SGB and thus serving as an internal control. Patient 2 sumitted for an additional SGB (SGB3). SGB3 produced a positive Horner s syndrome and anhidrosis, indicating a successful SGB. Relief of hot flash symptoms The effects of SGB on relief of hot flashes are summarized in Tale 2. Relief effects were present on the day of lock. Patients experiencing interrupted sleep all reported cessation of these prolems eginning on day 1 of treatment. For all patients, SGB1 caused asymptomatic periods of 2 5 weeks, followed y a period of intermittent relief. Patients returned for SGB2 at their discretion (i.e., when sujective hot flash symptoms elevated past mild). Successful SGB2 rought aout asymptomatic periods of 4 18 weeks, all of which were equal to or greater than the period of relief following SGB1. Patient 2, in whom SGB2 was unsuccessful, did not experience any relief of hot flash symptoms after the procedure. SGB3 was successful in Patient 2 and has provided 15 weeks of symptomatic relief to date. Thus, Patient 2 provided an internal control for this study, demonstrating that successful SGB is requisite for hot flash relief. Patient 5 also underwent SGB3 and reported 48 weeks of asymptomatic relief. We do not elieve that SGB cured this patient s hot flashes ut assume that the extended relief period overlapped with the natural time course of hot flash cessation in this patient. DISCUSSION The present case study demonstrates that SGB produces significant relief of severe hot flashes associated with menopause. The data in this paper represent an extended case study with 6 women. Although the patient population is small and homogeneous, these results provide sis for investigation of SGB as a nonhormonal treatment strategy for women who suffer from severe menopausal hot flashes. As an SGB may e considered y some to e invasive, we suggest that this intervention strategy e reserved for women in whom hormone therapy is contraindicated. Hot flashes are the most common symptom associated with menopause, occurring in 68% 82% TABLE 1. PATIENT INFORMATION AND EFFICACY OF STELLATE GANGLION BLOCK Results of SBG1 Results of SBG2 Results of SBG3 Patient Age Race Positive Horner s Anhidrosis Positive Horner s Anhidrosis Positive Horner s Anhidrosis 1 52 Caucasian Yes Yes Yes Yes 2 48 Caucasian Yes Yes Delayed No Yes Yes 3 54 Caucasian Yes Yes Yes Yes 4 49 Caucasian Yes Yes Yes Yes 5 56 Caucasian Yes Yes Yes Yes Yes Yes 6 58 Caucasian Yes Yes NA NA a Patient has not returned for additional SBG. NA, not applicale. 740 LIPOV ET AL. TABLE 2. TIMELINE OF HOT FLASH RELIEF IN (WEEKS) FOLLOWING STELLATE GANGLION BLOCK (SGB) SBG1 SBG2 SBG3 Mild Mild Mild Patient Asymptomatic HF a Time since SGB1 Asymptomatic HF Time since SGB2 Asymptomatic HF NA c NA NA a HF, hot flashes; NA, not applicale. Patient has not returned for additional SBG. c Patient moved out of state; no follow-up availale. of naturally menopausal women 1 and 90% of surgically menopausal women. 1 For women averse to hormone therapy (or in women for whom hormone therapy is contraindicated), there are few options. The overwhelming evidence suggests that heral remedies do not provide relief aove that of placeo, and lifestyle interventions are only moderately more effective than placeo (reviewed in refs. 4, 6, 10, and 11). Although SSRIs have proven to e moderately effective (reviewed in ref. 11), women with severe hot flashes need viale alternatives that provide adequate symptomatic relief. Given the marked similarity in symptomatic presentation of hyperhidrosis and hot flashes and the effectiveness of sympathectomy for relief of hyperhidrosis, we investigated the possiility that SGB would provide relief from hot flashes for significant durations of time. Our results demonstrate effective relief from severe hot flashes in menopausal women. SGB produced an asymptomatic period ranging from 2 to 5 weeks, followed y a period of mild symptoms lasting an additional 1 4 weeks. Repeat SGB produced equal or greater periods of relief. To our knowledge, there are no previous reports investigating SGB for relief of menopausal hot flashes. One case study descries the use of SGB to relieve similar symptoms in a man. Hendy et al. 13 reported a case of a 77-year-old man with severe episodes of flushing and sweating following testicular infarct. SGB reduced the frequency and severity of these events in this patient. The actual mechanism responsile for hot flashes remains elusive, although significant progress has een made. According to Freedman et al., 1,14,15 hot flashes likely result from a narrowing of the thermoneutral zone, which increases the susceptiility of the heat dissipation response to small fluctuation in core temperature (T c ). The thermoneutral zone is the area where T c fluctuates etween the shivering threshold and the sweat threshold. Hot flashes are preceded y a rise in T c that egins approximately 17 minutes efore the hot flash. During and after the hot flash, at which point T c crosses the sweat threshold, sweat rates increase. Following the heat dissipation response, T c falls elow the sweat threshold and reenters the thermoneutral zone. Often, T c falls elow the shivering threshold, causing reflex shivering and further illustrating the reduced size of the thermoneutral zone. Hot flash frequency varies according to a circadian oscillation, with a nadir in the morning hours and a peak in the late afternoon. Current evidence suggests that norepinephrine plays a central role in the etiology of hot flashes. Freedman 15 demonstrated an increase in plasma 3-methoxy-4-hydroxyphenylglycol (the main metaolite of central norepinephrine) levels following hot flashes. Estrogen, the most potent antihot flash agent, has een shown to increase hypothalamic norepinephrine. 16 Drummond and Finch 17 reported relief of facial temperature elevations and sweating in 9 patients with reflex sympathetic dystrophy following SGB, indicating the passage of sympathetic vasodilator fiers through the stellate ganglion. Ikeda et al. 18 reported the relief of climacteric psychosis following SGB with a concomitant decrease in plasma norepinephrine. In the current study, SGB ameliorated hot flashes in menopausal women. Taken SYMPATHETIC BLOCKADE RELIEVES HOT FLASHES 741 together, these data suggest that the stellate ganglion may e involved in the mechanisms controlling hot flashes. CONCLUSIONS Current evidence suggests that the most effective intervention for relief of hot flashes associated with menopause is hormone therapy; however, hormone therapy is associated with adverse side effects and has come under scrutiny following the results of the WHI study. Given the lack of efficacy associated with heral remedies and the limited results using nonhormone drug therapies (e.g., SSRIs), the current study presents a novel nonhormone-ased intervention for severe hot flash relief. Our results demonstrate significant immediate relief of hot flashes following SGB. In addition, multiple-week relief of severe menopausal hot flashes was accomplished after repeat SGB. These results suggest the need for additional research to evaluate the efficacy of this treatment strategy. Ideally, a randomized, controlled trial including placeo injections and extensive symptom reporting to produce level 1 evidence should e conducted to accept or refute the results of this multiple case study. At this point, we cannot recommend the adoption of this methodology in practice until further studies have een conducted. SGB does carry associated risk, ut these can e effectively avoided y the use of C-arm fluoroscopy y oard-certified anesthesiologists. REFERENCES 1. Freedman R. Physiology of hot flashes. Am J Hum Biol 2001;13: O Bryant SE, Palav A, McCaffrey RJ. A review of symptoms commonly associated with menopause: Implications for clinical neuropsychologists and other health care providers. Neuropsychol Rev 2003;13: Kronenerg F. Hot flashes: Epidemiology and physiology. Ann NY Acad Sci 1990;592: Fitzpatrick LA. Alternatives to estrogen. Med Clin North Am 2003;87: Koster A. Hormone replacement therapy: Use patterns in 51-year-old Danish women. Maturitas 1990;12: Barton D, Loprinzi C, Wahner-Roedler D. Hot flashes: Aetiology and management. Drugs Aging 2001;18: Lewis CE, Groff JY, Herman CJ, McKeown RE, Wilcox LS. Overview of women s decision making regarding elective hysterectomy, oophorectomy, and hormone replacement therapy. J Wom Health Gender-ased Med 2000;9(Suppl 2):S5. 8. Lauver DR, Settersten L, Marten S, Halls J. Explaining women s intentions and use of hormones with menopause. Res Nurs Health 1999;22: Austin PC, Mamdani MM, Tu K, Jaakkimainen L. Prescriptions for estrogen replacement therapy in ntario efore and after pulication of the Women s Health Initiative Study. JAMA 2003;289: Amato P, Marcus DM. Review of alternative therapies for treatment of menopausal symptoms. Climacteric 2003;6: Barton D, Loprinzi CL. Making sense of the evidence regarding nonhormonal treatments for hot flashes. Clin J Oncol Nurs 2004;8: De Salles A, Johnson, JP. Sympathectomy for pain. In: Winn H, ed. Youman s neurological surgery, 5th ed. Philadelphia: Saunders, 2003: Hendy MS, Cockrill B, Burge PS. The effects of naloxone infusion and stellate ganglion lockade on hot flushes in the human male. Maturitas 1985;7: Freedman RR, Norton D, Woodward S, Cornelissen G. Core ody temperature and circadian rhythm of hot flashes in menopausal women. J Clin Endocrinol Meta 1995;80: Freedman RR. Biochemical, metaolic, and vascular mechanisms in menopausal hot flashes. Fertil Steril 1998;70: Etgen A, Ungar S, Petitti N. Estradiol and progesterone modulation of norepinephrine neurotransmission: Implications for the regulation of female reproductive ehavior. J Neuroendocrinol 1992;4: Drummond PD, Finch PM. Reflex control of facial flushing during ody heating in man. Brain 1989; 112(Pt 5): Ikeda K, Isshiki A, Yoshimatsu N, Oumi A, Ito S, Ikeda T. [Three case reports of the use of stellate ganglion lock for the climacteric psychosis.] Masui 1993;42:1696. Address reprint requests to: Jamie T. Stark, Ph.D. Athletic and Therapeutic Institute 1408 Joliet Road, Suite 201 Romeoville, IL
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