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Background and objective Nasal symptoms of allergic rhinitis can be reduced with allergen‐specific subcutaneous immunotherapy (SCIT). However, the mechanisms underlying the effectiveness of SCIT for Japanese cedar pollinosis are not well understood. We studied changes in the numbers of metachromatic cells, eosinophils and neutrophils in nasal swabs following SCIT for Japanese cedar pollinosis. Methods Subjects were either untreated or given SCIT for 0.5 to 13 years duration. For the 2019 seasons, nasal swabs were taken in the pollinosis preseason (immunotherapy n = 36; untreated control, n = 62) and in the pollinosis season (immunotherapy n = 45; untreated control n = 46) and the numbers of mast cells, eosinophils and neutrophils assessed by microscopy. Results There were significant improvements in symptom severities following SCIT in comparison to untreated subjects (P, The number of metachromatic cells in nasal swabs in untreated subjects (B) and SCIT (C) for Japanese cedar pollinosis in pre‐season and in season.

Background As part of the planning for a future multicenter study, this preliminary clinical trial was performed to explore candidate biomarkers useful for predicting the therapeutic effects of sublingual immunotherapy (SLIT) for Japanese cedar pollinosis (JCP) using serum samples from patients. Methods This prospective study included patients undergoing SLIT for JCP at our hospital. All enrolled patients (n = 17) started SLIT between June and November of 2015. With informed consent from the patients, in January, March, and June of 2016, blood samples were obtained, and an inquiry was conducted using the Japan rhino-conjunctivitis quality of life questionnaire (JRQLQ). Based on the JRQLQ results, we allocated 6 patients with the most favorable results into the high response group (HRG), and 5 patients with the most unfavorable results into the poor response group (PRG). Subsequently, we compared the serum data between the two groups to identify useful biomarkers. Results The IL-12p70 and VEGF levels tended to be higher in the HRG than in the PRG in January, March and June (0.10 > p > 0.05). In addition, the IL-17 level was significantly higher (p Conclusions IL-12p70 and VEGF may be useful biomarkers for predicting the effects of SLIT. In addition, although it does not appear to be useful as a biomarker for evaluating treatment response at the start of SLIT, IL-17 may be useful as a biomarker after the beginning period of SLIT.

Background The human monoclonal antibody dupilumab blocks interleukin (IL)-4 andIL-13, key and central drivers of type 2 inflammation. Dupilumab, on background mometasone furoate nasal spray (MFNS), improved outcomes in the phase III SINUS-52 study (NCT02898454) in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP). This posthoc analysis of SINUS-52 examined whether eosinophilic status of CRSwNP was a predictor of dupilumab efficacy. Methods Patients were randomized 1:1:1 to dupilumab 300 mg every 2 weeks (q2w) until week 52; dupilumab 300 mg q2w until Week 24, then 300 mg every 4 weeks until week 52; or placebo (MFNS) until week 52. Coprimary endpoints were change from baseline in nasal polyps score (NPS), nasal congestion (NC), and Lund-Mackay score assessed by CT (LMK-CT) at week 24. Patients (n = 438) were stratified by eosinophilic chronic rhinosinusitis (ECRS) status according to the Japanese Epidemiological Survey of Refractory Eosinophilic Rhinosinusitis algorithm. Results Dupilumab significantly improved NPS, NC, and LMK-CT scores versus placebo at week 24 in all ECRS subgroups (p < 0.001), with improvements maintained or increased at week 52 (p < 0.001). There was no significant interaction between ECRS subgroup (non-/mild or moderate/severe) and dupilumab treatment effect for all endpoints at weeks 24 and 52 (p > 0.05), except LMK-CT at week 24 (p = 0.0275). Similar results were seen for the secondary endpoints. Dupilumab was well tolerated across all ECRS subgroups. Conclusion Dupilumab produced consistent improvement in symptoms of severe CRSwNP irrespective of ECRS status. Therefore, blood eosinophil level may not be a suitable biomarker for dupilumab efficacy in CRSwNP.

OBJECTIVES/HYPOTHESIS Dupilumab, which blocks the shared receptor component for interleukin-4 and interleukin-13, reduced polyp size, sinus opacification, and symptom severity, and was well tolerated in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) in the SINUS-52 study (NCT02898454). We assessed dupilumab in patients enrolled at Japanese centers. METHODS Patients on a background of mometasone furoate nasal spray, received dupilumab 300 mg every 2 weeks (q2w) for 52 weeks (Arm A); dupilumab 300 mg q2w for 24 weeks, followed by every 4 weeks (q4w) for 28 weeks (Arm B); or placebo (Arm C). Co-primary endpoints were week 24 nasal polyp score (NPS), nasal congestion (NC) score, and sinus Lund-Mackay CT (LMK-CT) scores. Symptoms, sense of smell, health-related quality of life, and safety were assessed during the 52-week treatment period. RESULTS Of 49 patients enrolled in Japan, 45 completed the study. Week 24 least squares (LS) mean improvement versus placebo were as follows: NPS (Arm A: -3.1, P

Background The influence of S-carboxymethylcystein (S-CMC) on the proliferation ability of goblet cells in nasal polyp epithelium in response to inflammatory stimulation was examined. Methods The subjects were patients with chronic paranasal sinusitis. An epithelial cell culture system was established using nasal polyp mucosa excised during endoscopic paranasal sinus surgery. The samples were divided into 4 groups (group a: control group, group b: 10 ng/mL tumor necrosis factor-α (TNF-α) treatment group, group c: 10-7 M S-CMC and 10 ng/mL TNF-α treatment group, group d: 10-5 M S-CMC and 10 ng/mL TNF-α treatment group). The total number of epithelial cells and number of goblet cells were measured under a microscope, and the ratio of goblet cells to the total number of epithelial cells was calculated. Results In group b, 10 ng/mL of TNF-α significantly increased the number of goblet cells compared with group a, suggesting involvement of TNF-α in goblet cell proliferation. In addition, the number of goblet cells significantly decreased in group d compared with that in group b, and it also decreased in group c compared with that in group b, although the difference was not significant, and the decrease was smaller than that in group d, suggesting that S-CMC inhibited goblet cell proliferation in a concentration-dependent manner. Conclusion TNF-α promoted goblet cell proliferation in nasal polyps, suggesting its influence on nasal polyp formation. As S-CMC inhibited inflammatory stimulation-induced goblet cell proliferation in nasal polyp epithelium, it may be useful for the treatment of sinusitis.

OBJECTIVES Macrolide therapy is an important conservative therapy for chronic rhinosinusitis, especially in Japan. The mechanism underlying this therapy involves anti-inflammatory and not antimicrobial activity. However, the administration of long-term low-dose macrolides (LTLMs) causes an increase in the number of antibiotic-resistant bacteria. EM900 is a derivative of erythromycin (EM), with anti-inflammatory but not antibacterial effects. It does not induce macrolide-resistant bacteria as shown by LTLM. In the present study, we analyzed the inhibitory effects of EM900 in comparison with those of clarithromycin (CAM) on inflammatory cytokine production in human nasal epithelial cells (HNEpCs). METHODS After HNEpCs were cultured for 4 days, CAM or EM900 was added into the culture, followed by stimulation with tumor necrosis factor (TNF)-α. Interleukin (IL)-8 and vascular endothelial growth factor (VEGF) levels were measured using real-time polymerase chain reaction (RT-PCR) and an enzyme-linked immunosorbent assay (ELISA). RESULTS Both the ELISA and RT-PCR showed that EM900 and CAM significantly inhibited IL-8 production in HNEpCs. In contrast, EM900 and CAM did not suppress the increased VEGF production when HNEpCs were stimulated with TNF-α. CONCLUSION EM900 showed an anti-inflammatory effect, such as that of CAM, due to the inhibitory effect on IL-8 production in HNEpCs.

BACKGROUND Health-related social media data are increasingly used in disease-surveillance studies, which have demonstrated moderately high correlations between the number of social media posts and the number of patients. However, there is a need to understand the causal relationship between the behavior of social media users and the actual number of patients in order to increase the credibility of disease surveillance based on social media data. OBJECTIVE This study aimed to clarify the causal relationships among pollen count, the posting behavior of social media users, and the number of patients with seasonal allergic rhinitis in the real world. METHODS This analysis was conducted using datasets of pollen counts, tweet numbers, and numbers of patients with seasonal allergic rhinitis from Kanagawa Prefecture, Japan. We examined daily pollen counts for Japanese cedar (the major cause of seasonal allergic rhinitis in Japan) and hinoki cypress (which commonly complicates seasonal allergic rhinitis) from February 1 to May 31, 2017. The daily numbers of tweets that included the keyword “kafunshō” (or seasonal allergic rhinitis) were calculated between January 1 and May 31, 2017. Daily numbers of patients with seasonal allergic rhinitis from January 1 to May 31, 2017, were obtained from three healthcare institutes that participated in the study. The Granger causality test was used to examine the causal relationships among pollen count, tweet numbers, and the number of patients with seasonal allergic rhinitis from February to May 2017. To determine if time-variant factors affect these causal relationships, we analyzed the main seasonal allergic rhinitis phase (February to April) when Japanese cedar trees actively produce and release pollen. RESULTS Increases in pollen count were found to increase the number of tweets during the overall study period (P=.04), but not the main seasonal allergic rhinitis phase (P=.05). In contrast, increases in pollen count were found to increase patient numbers in both the study period (P=.04) and the main seasonal allergic rhinitis phase (P=.01). Increases in the number of tweets increased the patient numbers during the main seasonal allergic rhinitis phase (P=.02), but not the overall study period (P=.89). Patient numbers did not affect the number of tweets in both the overall study period (P=.24) and the main seasonal allergic rhinitis phase (P=.47). CONCLUSIONS Understanding the causal relationships among pollen counts, tweet numbers, and numbers of patients with seasonal allergic rhinitis is an important step to increasing the credibility of surveillance systems that use social media data. Further in-depth studies are needed to identify the determinants of social media posts described in this exploratory analysis.

Background: Health-related social media data are increasingly used in disease-surveillance studies, which have demonstrated moderately high correlations between the number of social media posts and the number of patients. However, there is a need to understand the causal relationship between the behavior of social media users and the actual number of patients in order to increase the credibility of disease surveillance based on social media data. Objective: This study aimed to clarify the causal relationships among pollen count, the posting behavior of social media users, and the number of patients with seasonal allergic rhinitis in the real world. Methods: This analysis was conducted using datasets of pollen counts, tweet numbers, and numbers of patients with seasonal allergic rhinitis from Kanagawa Prefecture, Japan. We examined daily pollen counts for Japanese cedar (the major cause of seasonal allergic rhinitis in Japan) and hinoki cypress (which commonly complicates seasonal allergic rhinitis) from February 1 to May 31, 2017. The daily numbers of tweets that included the keyword “kafunshō” (or seasonal allergic rhinitis) were calculated between January 1 and May 31, 2017. Daily numbers of patients with seasonal allergic rhinitis from January 1 to May 31, 2017, were obtained from three healthcare institutes that participated in the study. The Granger causality test was used to examine the causal relationships among pollen count, tweet numbers, and the number of patients with seasonal allergic rhinitis from February to May 2017. To determine if time-variant factors affect these causal relationships, we analyzed the main seasonal allergic rhinitis phase (February to April) when Japanese cedar trees actively produce and release pollen. Results: Increases in pollen count were found to increase the number of tweets during the overall study period (P=.04), but not the main seasonal allergic rhinitis phase (P=.05). In contrast, increases in pollen count were found to increase patient numbers in both the study period (P=.04) and the main seasonal allergic rhinitis phase (P=.01). Increases in the number of tweets increased the patient numbers during the main seasonal allergic rhinitis phase (P=.02), but not the overall study period (P=.89). Patient numbers did not affect the number of tweets in both the overall study period (P=.24) and the main seasonal allergic rhinitis phase (P=.47). Conclusions: Understanding the causal relationships among pollen counts, tweet numbers, and numbers of patients with seasonal allergic rhinitis is an important step to increasing the credibility of surveillance systems that use social media data. Further in-depth studies are needed to identify the determinants of social media posts described in this exploratory analysis.

Objective Clarification of the association between the swallowing function and respiratory and phonatory functions. Methods The subjects were 30 patients with a chief complaint of swallowing disorder with clear consciousness capable of retaining a sitting position. Patients with organic and functional diseases of the larynx were excluded. Twenty-two and eight patients were male and female, respectively, and the mean age was 77.0 ± 14.6 years old. The chest expansion score was measured as an index of the respiratory function, and the maximum phonation time (MPT) was measured as an index of the phonatory function. The presence or absence of aspiration was judged using videoendoscopic swallowing study (VESS) and videofluoroscopic swallow studies (VFSS). The patients were divided into those with and without aspiration, and the chest expansion score and MPT were compared. In addition, the distance of laryngeal elevation was measured in the lateral view of VFSS, and its correlations with the chest expansion score and MPT were closely analyzed. To evaluate reliability of the test, the distance of laryngeal elevation and videoendoscopic score were compared between the presence and absence of aspiration. Results The distance of laryngeal elevation was significantly shortened and the videoendoscopic score was significantly higher in the group with aspiration, as previously reported. On comparison of the chest expansion score between the groups with and without aspiration, no significant difference was noted at the axillary or xiphoid process level, and shortening was significant only at the 10th rib level in the group with aspiration. On comparison of MPT, it was significantly shortened in the group with aspiration. In addition, a significant positive correlation with the distance of laryngeal elevation was noted in both chest expansion score and MPT. Conclusion It was suggested that declines of the respiratory and phonatory functions are risk factors of aspiration through limiting laryngeal elevation, and the chest expansion score at the 10th rib level and MPT are useful for screening of aspiration.

Vascular endothelial growth factor (VEGF) was identified in 1980s as a protein that increases vascular permeability and induces endothelial cell-specific mitosis. VEGF plays an important role in angiogenesis during the embryonic stage and in angiogenesis and in increasing vascular permeability during postnatal life, both physiologically and pathologically. Great progress has been made in studies of VEGF, mainly in the field of oncology, and VEGF-targeted therapy has been successfully used to treat patients with cancer. In research related to chronic inflammation, several reports concerning rheumatoid arthritis or retinopathy and VEGF have been published. In the lower respiratory tract, increased levels of VEGF have been detected in biological samples from patients with asthma. However, VEGF has not been studied in detail in upper-airway diseases, such as rhinosinusitis. This review article focuses on VEGF and allergic rhinitis to advance studies of VEGF in chronic inflammation of the upper respiratory tract. VEGF levels in nasal secretions and nasal lavage fluid were higher in perennial allergic rhinitis than in nonallergic rhinosinusitis, after, rather than before, the antigen provocation test. The major VEGF isoforms were confirmed to be VEGF₁₂₁ and VEGF₁₆₅ in allergic rhinitis. Expression of VEGF mRNA was higher in serous versus mucous acini. In allergic rhinitis, serous acini produced significant quantities of VEGF, which was hypersecreted after antigen provocation. VEGF seems to play an important role in the pathophysiology of allergic rhinitis. Modulation of VEGF function seems to contribute to the successful treatment of conditions with airway inflammation such as allergic rhinitis.

A 3-year-old girl presented with a transethmoidal meningoencephalocele manifesting as recurrent rhinorrhea. Initially, she developed meningitis, but after treatment she experienced rhinorrhea. Two months later, she again presented with rhinorrhea. Neuroimaging studies revealed a small protrusion (15 mm x 10 mm) at the roof of the ethmoidal sinus. Nasal endoscopy confirmed the diagnosis of meningoencephalocele. The operative findings revealed a small hole in the left olfactory bulb, which had descended into an enlarged foramen along with the arachnoid membrane. The left olfactory bulb was removed, and the enlarged foramina of the lamina cribrosa were covered with a frontal pericranial flap. The defect in the bone was very small, but contributed to the development of meningitis and leakage of the cerebrospinal fluid. Basal cephalocele should be considered in a patient with recurrent rhinorrhea and intracranial infections, even in the absence of any apparent anomaly.

Patients with allergic rhinitis are frequently complicated with some abnormal findings in the paranasal sinuses by X-ray examination. Recently this disease is being diagnosed as allergic rhinosinusitis. In many allergic rhinosinusitis cases, antiallergic drugs such as antihistamines and topical steroids comprise effective medication, but additional macrolide therapy for sinusitis has been reported to be in effective and unnecessary. In this study, the relationship between the type of X-ray shadow of sinuses and the efficacy of macrolide with antiallergic therapy in allergic rhinosinusitis cases was studied as a retrospective therapy. Subjects were 44 allergic rhinosinusitis patients aged from 4 to 60 years old enrolled in the outpatient clinic of the Kagoshima University Hospital ENT clinic. All the allergic rhinosinusitis cases were classified into 3 groups based on the type of X-ray shadow in the sinuses; mucosal thickness, polypous, and diffuse patterns. The X-ray findings were compared between before and after antiallergic therapy with/without macrolide in children and adult cases. X-ray examination revealed that the diffuse type was found in 18 of 42 (42%) children and in 26 of 136 (19%) adults cases. In child cases the diffuse type X-ray shadow was seen more often and macrolide therapy was thought to be more effective in combination with antiallergic medication than in adult cases. This study suggests the efficacy of macrolide therapy in the field of pediatric allergic rhinosinusitis.

Arytenoid dislocation is sometimes caused by endotracheal intubation or external cervical injury. Al-though the efficacy of closed surgery for this disease has been reported, the procedure is sometimes unsuccessful and various open procedures are necessary to improve the symptoms such as hoarseness. On the other hand, some patients with this disease were reported to be cured spontaneously. In the present study, we reported two patients with arytenoid dislocation caused by endotracheal intubation which were cured spontaneously. The first case was a 17-year-old man who complained of hoarseness after the surgery for hypospadias under general anesthesia. Endoscopic examination revealed the dislocation of the right arytenoid toward an anterior-medial position and dyskinesia of the right vocal cord. The hoarseness was spontaneously cured and completely disappeared on the 29th postoperative day. The examination with laryngeal fiberscope showed that the right arytenoid had returned to normal position. The second case was 46-year-old man who complained of hoarseness after laparoscopic surgery under general anesthesia. Laryngeal fiberscopy showed that his right arytenoid was dislocated toward an anterior-medial position. Hoarseness spontaneously disappeared 48 days after surgery. Several investigators have reported that spontaneous cure is frequently observed in anterior arytenoid dislocation, but not in posterior arytenoid dislocation, as shown in the present study. Those findings suggest that spontaneous reduction might be expected in many patients with anterior arytenoid dislocation.

頭頸部癌における進行癌症例に対して，転移リンパ節の臨床所見から内頸静脈を合併切除する根治的頸部郭清術を必要とすることも少なくない。しかし，術前に内頸静脈に浸潤があると判断されても，術後の病理組織学的検査では明らかな浸潤が認められないこともある。また，遊離皮弁による局所再建のために吻合血管を残す目的で内頸静脈の温存が必要となってくる場合，その是非が問題となる。さらに予後の面から，病理学的に腫瘍組織が内頸静脈内に露出していたりすると遠隔転移が多くなることが予想される。今回，我々は，内頸静脈を合併切除し根治的頸部郭清術を施行した症例について，病理学的に検査し，その後の経過も検討した。その結果，根治的頸部郭清術を施行する必要がある症例では，病理学的に内頸静脈に腫瘍の浸潤がなくても頸部再発率は高かった。遠隔転移については，病理学的に内頸静脈に直接浸潤があった症例が起こしやすい傾向にあった。術前の画像診断で内頸静脈への浸潤を判定するのは困難であったが，癒着がある症例では，内頸静脈静脈周囲に節外性に腫瘍細胞が存在するものとして治療する必要があると考えられた。

A case of suspected laryngeal tuberculosis accompanied by lung tuberculosis was reported in this paper. The patient was a 72 year-old male. He had developed hoarseness, sore throat and pain on swallowing, and consulted our clinic. Laryngoscopic examination showed swelling of the left arytenoid as well as laryngeal palsy. Pulmonary tuberculosis was diagnosed by microbiological identification of tubercle bacillus in the sputum. Although there was no evidence indicating laryngeal tuberculosis, local areas in the larynx were markedly improved after treating the patient with anti-tuberculosis chemotherapy. Consequently the patient was diagnosed as having laryngeal tuberculosis. Laryngeal tuberculosis is now rare in Japan, but it was suggested that careful attention should still be paid to the differential diagnosis of laryngeal inflammatory diseases.

We report a rare case of primary nasal and paranasal sinus cysts. The patient was a 4 year-old female, whose chief complaint was right exophthalmus. Although CT and MRI were performed preoperatively, primary cyst was not diagnosed at that time. Taking malignant tumors into consideration, endoscopic endonasal sinus surgery was performed under general anesthesia. Intraoperatively, multiple cystic lesions containing mucous effusion were observed and were opened to be a mono-cavity. After 10 months' follow up no recurrence has been noted. To our knowledge, this is the first case report of primary and multiple paranasal sinus cysts in a child.

A dermoid cyst is one of the most common head and neck cystic diseases and is usually found in the submandibular area. We report a rare case of double dermoid cysts that occurred in submental and submandibular spaces at the same time in a 53-year-old woman who visited our hospital with the chief complaint of cervical swelling. MRI and CT scans revealed two tumors in the submental and submandibular spaces. The submandibular tumor had a calcified lesion. The two tumors were removed under general anesthesia. The submental tumor strongly adhered to connective tissue such as muscles and the hyoid bone. No adhesion to the surrounding tissues was observed in the submandibular tumor. Both tumors had a white muddy substance in the inside and were diagnosed as epidermal type dermoid cysts histopathologically.

Objective/Methods: Long-term administration of clarithromycin has been reported to be effective in the treatment of chronic sinusitis. To investigate the mechanism underlying the anti-inflammatory activity of clarithromycin, the authors evaluated the effect of clarithromycin on the gene expression of proinflammatory cytokine and the DNA-binding activity of nuclear factor (NF)-κB in cultured human nasal epithelial cells and fibroblasts. Cells were incubated with endotoxin purified from nontypeable Haemophilus influenzae or interleukin (IL)-1β in the presence of clarithromycin. Results: Northern blot analysis revealed that clarithromycin suppressed IL-1β gene expression in human nasal epithelial cells stimulated by H influenzae endotoxin (HIE). Intercellular adhesion molecule-1 gene expression in nasal fibroblasts stimulated by IL-1β was also suppressed by clarithromycin. Furthermore, electrophoretic mobility shift assay demonstrated that clarithromycin reduced DNA-binding activity of NF-κB in both human nasal epithelial cells and fibroblasts stimulated by HIE or IL-1β, respectively. Conclusion: The present results suggest that clarithromycin may reduce gene expression of proinflammatory cytokines and adhesion molecules from nasal mucosa at the transcriptional factor level and exert an anti-inflammatory effect on nasal mucosa in chronic sinusitis.

Three temporal bones were obtained en bloc from autopsy cases with lepromatous leprosy from the middle cranial fossa side after removing the brain. After fixation with 10% formalin followed by sufficient decalcification, the specimens were embedded in paraffin en bloc and cut serially to stain every 10th section with hematoxylin and eosin (H&E) for anatomical orientation. An immunohistochemical study with anti-neurofilament, anti-MBP (myelin basic protein), anti-BCG (Bacillus Calmette-Gue'rin) and anti-PGL (Mycobacterium leprae-specific antiphenolic glycolipid-I) antibodies were performed to vestibular, cochlear and facial nerves, respectively, on the basis of anatomical orientation of the adjacent H&E sections. In one of three cases, positive staining by anti-PGL antibodies was recognized only in the facial nerve both in its internal auditory meatal and tympanic portions. However, even in this case, no neural damage was observed either by anti-neurofilament nor anti-MBP stainings. This finding supports the possibility of central neural infection by Mycobacterium leprae.

Penicillin-resistant Streptococcus pneumoniae (PRSP) is a frequently detected pathogen of intractable acute otitis media and is associated with prolonged or recurrent infection. The use of antibiotics has made the incidence of secondary acute mastoiditis following acute otitis media relatively rare, but when it does occur, its severe complications may be life-threatening. We report a case of pediatric recurrent acute mastoiditis caused by PRSP in a 6-year-old boy suffering from PRSP acute mastoiditis on 4 occasions, twice undergoing simple mastoidectomy. Although we initially suspected PRSP to be the chief factor in iterative infection, immunological analysis demonstrated significantly decreased IgG and IgA antibodies in serum and the patient was diagnosed as having common variable immunodeficiency (CVID). As the first middle ear infection occurred at the age of 6 and there was no history of upper respiratory tract infection, CVID may be the main pathological factor of recurrent mastoiditis, although infection occurred, only in the ear and did not involve other organs. This suggests that recurrent mastoiditis in the present case involved the coexistence of PRSP and CVID.

A series of 28 women who complained of an abnormal sensation in the throat were treated with Methermon ®-F and the clinical effects were analyzed. The overall effectiveness was excellent in 8 cases, good in 7, fair in 6 and poor in 1. Thus, the drug was clinically effective in 77.8%. The response was better in the climacteric age group than in other age groups. Kupperman's index was decreased in patients with excellent or good results. The increased in plasma concentration of luteinizing hormone (LH) and follicle stimulating hormone(FSH)correlated well with the clinical effect of this drug. As side effects, stomach discomfort was noted by two patients, one whom could not continue this drug.