2025 SMS建议：更年期潮热的管理

其他内分泌与代谢· 其他内分泌疾病 · 2025

5. Conclusion

In conclusion, we have developed a decision framework for treating VMS in women based on the C-SF scale score. (See Algorithm 1 Image) Decision Algorithm for VMS in women.

1. Initial Assessment

Women suffering VMS Follow lifestyle advice:

○ Reduce consumption of tobacco, caffeine, and alcohol. ○ Maintain adequate weight. ○ Consume a Mediterranean diet and fruits.

2. Evaluate C-SF Menopausal Domain Scores

If Menopausal domain ≤ 25 (Mild)

○ Follow the path for mild symptoms ○ If after 12 weeks there is no improvement, move on to the next step (lifestyle changes continue) By following these steps and recommendations, a structured and logical approach to managing VMS in women can be ensured.

Contributors

Maria Fasero contributed to conception and design of the idea, coordination and preparation of manuscript, manuscript editing, and was a coordinator of Menoguide Hot flushes. Laura Baquedano contributed to preparation of manuscript and was a member of menoguide Hot flushes. Maria Teresa sanchez contributed to preparation of manuscript and was a member of menoguide Hot flushes. Isabel Gippini contributed to preparation of manuscript and was a member of menoguide Hot flushes. Danilo Fuentes contributed to preparation of manuscript and was a member of menoguide Hot flushes. Concha Navarro contributed to preparation of manuscript and was a member of menoguide Hot flushes. Estanislao Beltran contributed to preparation of manuscript and was a member of menoguide Hot flushes. Mariella Lilue contributed to preparation of manuscript and was a member of menoguide Hot flushes. Iris Porcel contributed to preparation of manuscript and was a member of menoguide Hot flushes. Carmen Pingarron contributed to preparation of manuscript and was a member of menoguide Hot flushes. Mercedes Herrero contributed to preparation of manuscript and was a member of menoguide Hot flushes. Pablo Romero contributed to preparation of manuscript and was a member of menoguide Hot flushes. Maria Teresa Ortega contributed to preparation of manuscript and was a member of menoguide Hot flushes. Maria Emilia Carretero contributed to preparation of manuscript and was a member of menoguide Hot flushes. Nicolas Mendoza contributed to external review. Santiago palacios contributed to external review. Pluvio Coronado contributed to external review.

|AUTHOR|N|STUDY|COMPARATOR GROUPS|RESULTS|RECOMMENDATION| |---|---|---|---|---|---|

||||||GRADE|

|Berin E et al.||RCT|Resistance training 3 v/ week/ 15 week|Improvement in HRQoL in menopause|STRONG IN FAVOR|

|[17]||||||

|Berin E et al.||RCT|Resistance training 3 v/ week/ 15 week|Decrease in the frequency of moderate and|STRONG IN FAVOR|

|[18]||||severe VMS||

|Baena-García L.||RCT|59 multicomponent exercise versus 53 tips|Positive effect on menopause symptoms and|STRONG IN FAVOR|

|et al.||||psychological state||

|[19]||||||

|Capel-Alcaraz AM||SR|Effects of strength exercises versus other types|Strength exercises are beneficial for|WEAK IN FAVOR|

|et al.|||of interventions|menopause symptoms||

|[20]||||Unclear evidence on types of strength||

|||||exercise.||

|Daley AJ et al.||SR|2 groups Exercise+menopause-specific|Insufficient evidence to demonstrate PE as|STRONG AGAINST|

|[21]|||information vs Exercise + social support|an effective treatment of VMS||

||||groups Interventions 6 months.|||

|Daley AJ, et al.||RCT|3 groups 87 women, one with|PE is not effective for HF or NS|STRONG AGAINST|

|[22]|||recommendations, another attendance at PE|||

||||classes, another control|||

|Luoto R et al.||RCT|88 vs 88 Unsupervised aerobic exercise|Aerobic training decreases the frequency of|STRONG IN FAVOR|

|[23]|||50 min/ 4 times a week/6 month. Telephone|VMS and improves HRQoL in overweight||

||||questionnaire|women.||

|Mansikkamäki K,||RCT|88 vs 88 Unsupervised aerobic exercise|Aerobic training for 6 months improves|STRONG IN FAVOR|

|et al.|||50 min/ 4 times a week/ 6 months. Telephone|sleep quality and reduces VMS in||

|[24]|||questionnaire|symptomatic women||

|Aiello EJ et al.||RCT|Overweight postmenopausal women: 87|Significant increase in the intensity of VMS|WEAK AGAINST|

|[25]|||moderate intensity exercise vs 86 control with|and a decrease in the risk of memory||

||||stretching for 12 months|problems||

|Lindh-Astrand L||RCT|Sedentary postmenopausal women: 15 PE vs|PE improves VMS and HRQoL|WEAK IN FAVOR|

|et al.|||15 E2 vs 45 control for 12 weeks|||

|[26]||||||

|Herber-Gast GC|||||WEAK IN FAVOR|

|et al.||||||

|[27]||||||

|Flor-Alemany M||TS|A food frequency questionnaire|Mild symptoms of menopause benefit from|WEAK IN FAVOR|

|et al.||||lower consumption of poultry and low-fat||

|[28]||||dairy products and higher consumption of||

|||||vegetables and soy milk.||

|Kroenke CH et al.||PS|Diet intervention versus control|Weight loss decreases VMS in|STRONG IN FAVOR|

|[29]||||postmenopausal patients||

|Barnard ND et al.||RCT|Changes in diet with increased consumption of|Reduces frequency and severity of VMS and|STRONG IN FAVOR|

|[30]|||fruits, vegetables and whole grains compared|associated symptoms||

||||to the control group|||

|Jenabi E and J.||MT|Effect of former smoking and current smoking|Ex-smokers are associated with a higher risk||

|Poorolajal|||on the risk of hot flushes in midlife women.|of VMS||

|[31]||||||

|TS|Pre and perimenopausal|Smoking and depressive symptoms were| |---|---|---|

|[32]||associated with the risk of suffering from|

|||VMS.|

||OBS|45-50 years in 1996. Follow-up 15 years/|HF and NS less frequent in highly educated|STRONG IN FAVOR| |---|---|---|---|---|

|[33]||questionnaires every 3 years|women and more frequent in obese women,||

||||current smokers, drinkers, perimenopausal,||

||||postmenopausal, weight gain, premenstrual||

||||tension, with diabetes and early age at first||

||||pregnancy.||

|[34]|||were independent risk factors for||

||||experiencing VMS.||

|[35]|||alcohol consumption predict VMS and NS.||

||||Anxiety, depressed mood, years since||

||||menopause, and education predicted||

||||current prevalence of VMS. HRT users who||

||||discontinued treatment had more VMS.||

|[36]||lifetime abstainer, former or current drinker,|increased risk of early-onset VMS.||

|||categorized as light, moderate, high and very|Abstaining from alcohol consumption may||

|||high.|help prevent VMS in premenopausal women||

|Jay Kandiah and|TS|Questionnaire|Aerobic PA, caffeine, and alcohol||

|Valerie Amend|||consumption are predictors of VMS severity.||

|[37]|||||

|et al.|postmenopausal|||status are the main factors associated with||

|[38]||||sleep disorders.||

|et al.|postmenopausal|||to BMI ≥ 25 and alcohol consumption of 1-5||

|[39]|468 perimenopausal|||drinks per week. In postmenopausal||

|||||women, high fat intake was related to VMS||

|Anderson DJ|21460|TS|Pooled data on 21,460 midlife women from 8|BMI ≥ 25 and smoking increased the risk of||

|et al.|||studies|VMS in a dose-related manner.||

|[40]||||Maintaining a normal weight before the||

|||||menopausal transition and quitting smoking||

|||||before age 40 mitigates the excess risk of||

|||||VMS in midlife.||

||334|TS|A cross-sectional sample of 334 black and|Natural menopause < 52 years, low|WEAK IN FAVOR| |---|---|---|---|---|---|

|[42]|||white, naturally menopausal women was|educational level, and lean women who||

||||selected from a control group in a population-|smoked in the premenopausal period were||

||||based study of reproductive cancers in central|more likely to experience VMS. Among non-||

||||North Carolina.|smokers, BMI has no effect on VMS. Alcohol||

|||||consumption has a positive relationship||

|||||with VMS. Menarche < 12 years and a||

|||||history of irregular cycles were related to a||

|||||decrease in VMS.||

|[43]|45-65 years||selected demographic factors, reproductive|VMS and tobacco use||

||||history, and behavioral factors|||

|Green SM et al.||RCT|CBT versus no treatment Follow-up at 12|Effective in improving VMS, depressive|WEAK IN FAVOR|

|[44]|||weeks and 3 months|symptoms, sleeping difficulties and sexual||

|||||concerns.||

|[45]||||mild-moderate VMS. Efficacy was greater||

|||||for VMS than for other menopausal||

|||||symptoms induced by oncological||

|||||treatment.||

|Ayers B et al.|140|RCT|Group CBT vs PCB|CBT improves VMS and SN in women||

|[47]|||CBT group: weekly 2-hour sessions,|during the menopause and postmenopause||

|||||transition. The findings suggest that CBT is||

|||||brief and effective in treating VMS.||

||281|SR|Cochrane Database of Systematic Reviews|There is no evidence of the effectiveness of|STRONG AGAINST| |---|---|---|---|---|---|

|[48]||||relaxation techniques in the treatment of||

|||||VMS.||

|[49]||||||

|Barton DL et al.||RCT|4 groups:|Hypnosis reduces VMS as much as|WEAK IN FAVOR|

|[50]|||75 mg venlafaxine+ hypnosis,|venlafaxine alone, but the combination of||

||||75 mg venlafaxine + sham hypnosis,|both does not reduce it more.||

||||PCB+ hypnosis pill|||

||||PCB + simulated hypnosis|||

|Palma F et al.||RCT|3 groups|Greene scale score improvement: 44 % HRT,|WEAK IN FAVOR|

|[53]|||3 months acupuncture session /week|41.3 % acupuncture and 17 % isoflavone.||

||||75 mg isoflavone/12 hours|In a secondary analysis, acupuncture was||

||||0.30 mg ECE + 1.5 mg MPA|more effective than phytoestrogens.||

|[54]||||treatment but less effective than HRT.||

|[55]|||G1 48 weeks acupuncture + 24 weeks|menopausal symptoms during the transition||

||||simulated acupuncture|menopause.||

||||G2 on the contrary|||

|[56]|> HF/day|||breast Ca was reduced in the acupuncture||

|||||group.||

|Ee C et al.|327|||||

|[57]|> years|||||

||> HF/day|||||

|.| |---|

|continued )|||||| |---|---|---|---|---|---|

|[90]||||||

|Aghamiri V et al.|120|RCT|PCB|Reduction of VMS versus PCB.|STRONG IN|

|[91]|||||FAVOR|

|SAGE||||||

|Zeidabadi A et al.|66|RCT|PCB|Reduction of VMS versus PCB.|STRONG IN|

|[92]|||||FAVOR|

|Wilfried et al.|80|RCT|PCB|Reduction of VMS compared to PCB.|STRONG IN|

|[93]|||||FAVOR|

|Cytoplasmatic pollen||||||

|extract||||||

|Winther K et al.|64|RCT|PCB|Reduction of VMS versus PCB.|STRONG IN|

|[94]|||||FAVOR|

|[95]||4 POE||Indicated in patients with breast|FAVOR|

|||||cancer.||

|[96]|||Evaluation by comparison with VAS at days 0, 30, 60 and 90|||

||||of treatment|||

|VMS: Vasomotor symptoms; PCB: Placebo; HF: hot flushes; E2-TDM: transdermal estrogens; RCT: Randomized clinical trial; HRQoL: Health relates quality of life's; SR:||||||

|Systematic review; AEEM: Spanish menopause society; Ca: Cancer; IF: isoflavones; NS: night sweets; GEN: genistein; DAID: Daizcein; IF: isoflavones; PUFA: unsat-||||||

|Study|DESIGN|N|PCB|Type of treatment|Conclusion|Recommendation| |---|---|---|---|---|---|---|

|Route of administration|RCT|727|Yes|ECE+PG|ECE and E2 TSD both effective in VMS v|STRONG IN|

|Santoro N et al.|3 groups, 4 years|||E2 TSD+MPG cyclic|PCB|FAVOR|

|[97]|||||||

|ROUTE OF|OBS,|22|22|22|No|E2 TSD low dose|

|ADMINISTRATION|2 groups, 12|||||FAVOR|

|Shulman LP et al.|months||||||

|[98]|||||||

|DOSE|RCT,|425|Yes|E2 0.025 +LNG|E2 0.014mgr/day effective|STRONG IN|

|Bachmann GA et al.|3 groups, 4 years|||E2 0.014 +LNG||FAVOR|

|[99]|||||||

|DOSE|RCT,|176|Yes|E2 0.025|Improvement of VMS in all group's vs|STRONG IN|

|Utian WH et al.|4 groups, 3 doses,|||E2 0.05|PCB.|FAVOR.|

|[100]|3 years|||E2 0.100|Low doses just as effective and fewer side||

||||||effects||

|DOSE|RCT,|484|Yes|E2 gel various doses|Lower doses, greater adherence after 12|STRONG IN|

|Simon JA et al.|4 groups, 4 doses,||||weeks with fewer side effects|FAVOR|

|[101]|12 weeks.||||||

|DOSE|RCT,|647|Yes|E2 + 100 mg MPG|Improvement at all doses vs PCB|STRONG IN|

|Kaunitz AM et al.|4 groups, 12|||||FAVOR|

|[110]|months, 3 years||||||

|ENDOMETRIAL|RCT,|310|No|E2 + DG/E2 + NETA|NETA less bleeding than DG|STRONG IN|

|PROTECTION|2 groups, 2 doses,||||Both relieve VMS|FAVOR|

|Saure A et al.|12 weeks||||||

|[102]|||||||

|ENDOMETRIAL|RCT,|2673|Yes|ECE+MPA|Low doses = effective|STRONG IN|

|PROTECTION|5 groups, 3 doses,||||High doses + abandonment due to side|FAVOR|

|Utian W.H. et al.|12 months||||effects.||

|[104]|||||||

|ENDOMETRIAL|RCT|119|Yes|E2 + NETA 3 doses|NETA 0.5 less bleeding|STRONG IN|

|PROTECTION|||||All doses more effective than PCB|FAVOR|

|Baerug U et al.|||||||

|[103]|||||||

|ENDOMETRIAL|PCS,|111|No|E2 0.5 mg +NETA 0.1 mg|High rate of amenorrhea|WEAK IN FAVOR.|

|PROTECTION|52 weeks||||||

|Mattson LA et al.|||||||

|[107]|||||||

|ENDOMETRIAL|RCT,|446|No|E2 1 mg+NETA continuous|Better continuous NETA bleeding rates|STRONG IN|

|PROTECTION|2 groups, 9 months|||EEC 0.025 +MPA 5 mg cyclic|than sequential MPA|FAVOR|

|von Holst T et al.|||||||

|[105]|||||||

|ENDOMETRIAL|SR||No|E2 1 mg+MPG|Greater amenorrhea E2 + MPG or|STRONG IN|

|PROTECTION|45 articles (most|||ECE 0.025 +NETA 0.5|ECE+NETA|FAVOR|

|Pickar JH et al.|RCTs)||||Low doses||

|[108]|||||Oral better than TSD||

|TIBOLONE|AEEM position||||Infrequent bleeding (+ in young people)|STRONG IN|

|Mendoza N et al.|statement|||||FAVOR|

|[122]|||||||

|TIBOLONE|RCT|396|Yes|Tibolone 2.5 mg and 1.25 mg|2.5 mg more effective|STRONG IN|

|Swanson SG et al.||||+ PCB|Tibolone = E + PG or E alone|FAVOR|

|[121]|||||||

|TSEC SMART 1|RCT,||Yes|BZA 40 mg or 20 mg /ECE|Endometrial hyperplasia < 1 %|STRONG IN|

|Levine JP.|12 and 24 months|||0.45 mg or 0.625 mg|Protection all doses|FAVOR|

|[123]|||||||

|TSEC SMART 2||332|Yes|BZA 40 mg or 20 mg|Both doses better than PCB|STRONG IN|

|Levine JP et al.||||+ECE 0.45 mg or 0.625 mg|BZA all doses endometrial protection|FAVOR|

|ORAL MPG ALONE|SR|601|Yes|5-60 mg MPG TDM|Beneficial effect of oral MPG in higher|STRONG IN|

|Dolitsky SN et al.|892 studies|||10.20 mg oral MPA 300 mg|doses (300 mg) in the treatment of VMS|FAVOR|

|[125]|1980-2020|||oral MPG|||

|||||21 days-12 months (average:|||

|||||12 weeks)|||

|ORAL MPG ALONE|RCT|133|Yes|300 mg MPG|300 mg oral MPG is effective in the|STRONG IN|

|Hitchcock CL et al.|2003-2009|||PCB|treatment of VMS|FAVOR|

|[124]|||||||

|THROMBOSIS|CCS,|186|Yes|E2 TSD+MPG|MPG does not alter parameters.|STRONG IN|

|Canonico M.|3 groups,|||E2|Norpregnanes can activate protein C and|FAVOR|

|[118]||||TSD+norpregnane|coagulation||

||||||E2 TSD+MPG safer||

|THROMBOSIS|SR,||||E2 TSD safer and less thrombotic|STRONG IN|

|Oliver-Williams C|33 studies|||||FAVOR|

|[106]|||||||

|THROMBOSIS|R|||Various doses of E and PG|Oral E2 more thrombotic than TSD|WEAK IN FAVOR|

|Shufelt CL et al.||||and various routes|MPG and pregnanos derivatives safer than||

|[119]|||||norpregnanos||

||||||E2 TSD less coagulation effect, stroke and||

||||||DVT vs oral||

|THROMBOSIS|CCS|5790 DVT||HT 90 days oral /TSD,|Oral E2 more risk of DVT|WEAK IN FAVOR|

|Vinogradova Y et al.||21670||various doses|ECE more risk than E2 ECE+PG more risk||

|[120]||controls|||ECE+MPA more risk||

||||||E2 + NETA or DG lower risk||

||||||E2 TSD less risk||

||||||Tibolone no risk||

||||||More DVT in oral and more doses of E2||

|LNG IUD|R|200|||Perimenopause: more effective in bleeding|WEAK IN FAVOR|

|Joo JK et al.|||||IUD plus E2 safe endometrial protection||

|[112]|||||||

|LNG IUD|RCT|200||oral LNG+E2 IUD|All endometrial protection|STRONG IN|

|Boon J et al.||||E2 2 mg/NETA1 mg cyclic|IUD decreased bleeding|FAVOR|

|[113]||||(13-22)|||

|||||E2 2 mg/NETA1 mg cyclic|||

|||||(1-21)|||

|||||(22-28)|||

|LNG IUD|RCT|40|40|40||oral LNG+E2 IUD|

|Anderson K et al.||||E2 2 mg/NETA 1 mg cyclic|endometrial proliferation and reduces|FAVOR|

|[114]||||(13-22)|bleeding||

|||||E2 2 mg/NETA 1 mg cyclic|Group with cyclic NETA, regular bleeding||

|||||E2 2 mg/NETA 1 mg cyclic|||

|LNG IUD|SR|554||397 IUD|IUD non-endometrial proliferation.|STRONG IN|

|Depypere H et al.|6 pivotal studies|||157 oral sequential PG|PG sequential proliferation 11.1 % at 2|FAVOR|

|[115]|||||years||

|LNG IUD|Open,|||IUD+E2 (oral, TSD,|76 and 79 % amenorrhea 20 and 34|WEAK IN FAVOR|

|Suhonen S, et al.|uncontrolled|||subdermal)|months||

|[116]|study||||Spotting 1-2 days/month||

|LNG IUD||200||E2 2 mg+NETA 1 mg 13-22|IUD 38 % amenorrheic VS NETA 0 %|WEAK IN FAVOR|

|Boon J, et al.||||(n100)|||

|[117]||||E2 2 mg+IUD (n100)|||

|COMPOSED OF|SR||||They do not meet FDA profiles|STRONG|

|BIOIDENTICAL|||||Saliva/serum steroid concentration|AGAINST|

|HORMONES|||||correlation inconclusive||

|Stanczyk et al.|||||Individualized preparations are not||

|[126]|||||standard, not regulated||

|AUTHOR|N|TYPE OF STUDY|COMPARATOR|COMMENTS| |---|---|---|---|---|

||||GROUPS||

|||blinded extension phase|30 mg: 173|severe VMS vs PCB at weeks 4 and 12|

|SKYLIGHT¡1 [132]||(Phase 3).|Fezoniletant||

|||(NCT04003155)|45 mg: 174||

||||PCB: 175||

|||blinded extension|30 mg: 166|severe VMS vs PCB at weeks 4 and 12|

|SKYLIGHT¡2 [133]||(Phase 3).|Fezoniletant|Fezolinetant 45 mg reduces sleep disturbances|

|||(NCT04003142)|45 mg: 167||

||||PCB: 167||

|[134]||(Phase 3).|30 mg: 611|Fezolinetant|

|SKYLIGHT¡4||(NCT04003389)|Fezoniletant||

||||45 mg: 609||

||||PCB: 611||

|MOONLIGHT¡1||open label extension phase of|30 mg: 150|baseline in East Asian women vs placebo|

|[135]||12 weeks|PCB: 151||

|||(Phase 3).|||

|||(NCT04234204)|||

|||(Phase 3).|30 mg: 150|tolerated in Chinese women|

|MOONLIGHT¡3||NCT04451226||.|

|[136]|||||

|||(Phase 3b)|45 mg: 226|in a population unsuitable for HRT|

|||(NCT05033886)|PCB: 226.||

|2024||(Phase 3)|PCB|Change in HT frequency and severity from baseline to|

|||(NCT06440967)||weeks 4 and 12 in women with hormone receptor-positive|

|||||BC who are receiving adjuvant endocrine therapy|

|2023||(Phase 2b)|40 mg: 31|and 160 mg at week 4 and with 120 mg at week 12.|

|SWITCH¡1 [142]||NCT03596762|Elinzanetant||

||||80 mg: 17||

||||Elinzanetant||

||||120 mg: 52||

||||160 mg: 52||

||||PCB: 47||

|Participating countries:||week active-treatment|120 mg: 199|weeks.|

|Austria, Czechia, Greece, Hungary, Israel, Italy,||extension|PCB: 197||

|Netherlands, United States, Spain||(Phase 3)|||

|OASIS ¡1 [178]||(NCT05042362)|||

|2024||week active-treatment|120 mg: 200|weeks|

|Participating countries:||extension|PCB: 200||

|Canada, Czechia, Germany, Italy, Norway,||(Phase3)|||

|Poland, Portugal, Slovakia, Switzerland, United||(NCT05099159)|||

|States|||||

|OASIS ¡2|||||

|Participating countries:||(Phase 3).|120 mg|baseline to week 12.|

|Belgium, Bulgaria, Canada, Denmark, Finland,||(NCT05030584)|PCB||

|Poland, Spain, United Kingdom, United States|||||

|OASIS¡3|||||

|Participating countries:||(Phase3)|120 mg|by adjuvant endocrine therapy in women with or at high|

|Austria, Belgium, Canada, Finland, Hungary,||(NCT05587296)|PCB|risk of developing hormone receptor-positive BC from|

|Ireland, Israel, Italy, Kazakhstan, Poland,||||baseline to weeks 4 and 12|

|Portugal, Romania, Spain and the United|||||

|Kingdom|||||

|OASIS 4|||||

|VMS: Vasomotor symptoms; HF: Hot flushes; HRT: Hormone replacement therapy; RCT: Randomized control tried; PCB: placebo; BC: breast cancer.|||||

|AUTHOR|N|TYPE OF|COMPARATOR GROUPS|CONCLUSIONS|ADVERSE EFFECTS| |---|---|---|---|---|---|

|||STUDY||||

|PAROXETINE||||||

|Nelson et al.|316|SR-MT|Comparison between doses of|There are no differences between doses||

|[149]||(2 RCTs)|paroxetine|in the treatment of VMS.||

||||• 10 mg|||

||||• 25 mg|||

||||Peri and post menopause|||

|[150]||(2 RCTs)|Sertraline|the treatment of VMS.|Fatigue (3.4 % vs 1.5 % PCB)|

||||Fluoxetine||Dizziness (2.0 % vs 0.8 % PCB)|

||||Escitalopram||Abandonment treatment higher on paroxetine|

||||Citalopram||Increased risk of mortality in women with|

||||PCB||breast cancer treated with tamoxifen (drug|

||||||interaction)|

|[151]||(5 RCTs)|day|Not effective in nocturnal awakenings|dizziness|

||||PCB|||

||||Post-menopausal|||

||||(1 surgical menopause trial)|||

||||6-16 months|||

|[152]||and crossover|Paroxetine 20 mg/day|Effective in the first week and|mainly in the 20 mg/day group|

|||RCT|PCB|maintained until the end|Dry mouth and nausea|

||||BC survivors|Both doses are effective, but 10 mg/day||

||||6 weeks|is better tolerated.||

|[153]||double blind|release)||Headache and dizziness|

|||RCT|12.5 mg/day|||

||||25 mg/day|||

||||Symptomatic women after|||

||||discontinuation of hormonal|||

||||therapy|||

||||6 weeks|||

|Simon et al.|42|42|RCT|Paroxetine (25 mg/day)|VMS decreases in both paroxetine and|

|[154]|||Raloxifene (60 mg/day)|PCB and not in raloxifene||

||||16 weeks|||

|FLUOXETINE||||||

|Nelson et al.|316|SR -MT|Fluoxetine 20 mg/day|No significant reduction in VMS||

|[149]||(2 RCTs)|Peri and post menopause|compared to PCB||

||||Women with and without a|No more effective than other drugs||

||||history of BC|||

|Loprinzi et al.||Double-blind|Fluoxetine 20 mg/day|VMS reduction in fluoxetine greater||

|[156]||crossover RCT|PCB|than in PCB||

||||(4 weeks)|||

||||Women with a history of|||

||||breast cancer or concerned|||

||||about the risk associated with|||

||||HRT|||

|[157]|||increasing to 20 mg/day at 1|PCB||

||||month and 30 mg/day at 6|||

||||months|||

||||Citalopram|||

||||Women without history of|||

||||cancer (9 months of follow-|||

||||up)|||

|[158]|||Black Cohosh (4 0 mg/day)|cohosh.|in both groups|

||||6 months|Best Fluoxetine Depression Scale||

|VENLAFAXINE AND||||||

|DESVENLAFAXINE||||||

|Nelson et al.|247|SR -MT|Venlafaxine|It did not show effectiveness in reducing||

|[149]||(2 RCTs)|PCB|frequency, but it did show effectiveness||

|||||in comparison to PCB.||

|[159]||double blind|Oral 17β-estradiol 0.5 mg/day|estradiol are more effective than PCB;||

||||PCB|the second being somewhat more||

||||Peri and postmenopause|effective than the first||

||||> 2 episodes/day|||

||||8 weeks|||

||||||(continued on next page)|

|(continued )|||||| |---|---|---|---|---|---|

|[160]||(6 RCTs)|PCB|frequency and intensity|cerebrovascular or hepatic risk|

||||26 weeks|||

|Sun et al.||3RCT|Desvenlafaxine (150 mg/day)|Efficacy of desvenlafaxine in reducing|Nausea, constipation, diarrhea, dry mouth,|

|[160]|||PCB|frequency and intensity|drowsiness, asthenia, dizziness, insomnia, etc.|

|Pinkerton et al.||RCT, double|Desvenlafaxine (100 mg/day)|Effectiveness of desvenlafaxine in||

|[161,162]||blind|PCB|reducing the frequency and intensity of||

||||Postmenopause|VMS.||

||||12 weeks|||

|A.|tto.||50 mg/day|moderate and severe VMS for doses of|anorexia, constipation, diarrhea, dry mouth,|

|[163]|1665||100 mg/day|100 and 150 mg/day|nausea, dizziness, insomnia, drowsiness and|

||PCB||150 mg/day|Reduction of associated nocturnal|mydriasis) that determine the suspension of|

||||200 mg/day|awakenings.|treatment|

||||> 12 weeks|||

|CITALOPRAM AND||||||

|ESCITALOPRAM||||||

|Shams et al.|2069|SR -MT|• Citalopram (20 mg/day)|Frequency of VMS: No significant||

|[150]||(3RCT)||differences compared to PCB,||

||||• Fluoxetine|fluoxetine, sertraline, paroxetine and||

||||• HRT|escitalopram||

||||• PCB|||

||||Peri and postmenopause|||

|Shams et al.||SR -MT|• Escitalopram 10 and|The weighted average differences||

|[150]||(2RCT)|20 mg/day|indicate that there are no significant||

||||• PCB|differences compared to PCB||

|Carpenter et al.||RCT|• Escitalopram (10-20 mg/|Improved HRQoL in women|Not reported|

|[164]|||day)|||

|GABAPENTIN AND||||||

|PREGABALIN||||||

|[167]||RCT|• PCB||gabapentin and 3 % in PCB.|

||||Postmenopause|||

|Pandya et al.||Double blind|• Gabapentin 300 or 900 mg/|VMS intensity decreases; frequency only|More drowsiness and fatigue at higher doses.|

|[168]||RCT|day (in three doses)|at the highest dose -900 mg/day-)||

||||Women with BC|||

|[169]||RCT|• ECE 0.625 mg/day|with similar efficacy to gabapentin and|higher incidence in the group treated with|

||||• PCB|estrogens and superior to PC|gabapentin|

|Butt et al.||Double blind|• Gabapentin 900 mg/d in|Decreases the frequency of VMS.|Dizziness (18 %), instability (14 %) and|

|[170]||RCT|three doses||drowsiness (12 %) during the first week that|

||||• PCB||disappear after two weeks.|

||||45-65 years|||

|Loprinzi et al.||Double-blind|• Pregabalin 150 mg/d or|Decreases the frequency and intensity of|Better tolerated dose of 150 mg/d|

|[156]||phase III RCT|300 mg/d|VMS||

|[171]||RCT|• E2 25 µg/d TSD, 1 patch|VMS with similar effectiveness to E2.|gabapentin group|

||||weekly||Mastodynia, vaginal spotting in the E2-treated|

||||||group.|

|[172]|||• PCB|VMS||

|Pinkerton et al.||Phase III RCT|• Gabapentin 600 mg/|Decreases the frequency and intensity of|More about abandonment of treatment|

|[173]|||morning and 1200 mg/|VMS|regarding PCB. Dizziness, headache and|

||||night||drowsiness.|

||||• PCB||Adverse effects decrease significantly after|

||||||several weeks of treatment.|

|[174]||RCT|PCB + Ca;|VMS. Maximum effect after 3 months.||

|CLONIDINE||||||

|Nelson et al.||SR-MT (4|Clonidine:|No decrease in frequency and intensity|Does not affect BP at the doses tested|

|[149]||RCTs)|• 0.1 mg/ day)|of VMS vs PCB||

||||• 0.05-0.15 mg/day|||

|[165]|||• Venlafaxine (37.5 twice|clonidine in the treatment of VMS||

||||daily)|||

|○ Follow the path for moderate-severe symptoms| |---|

|3. Mild Symptoms Management|

|• Start with Natural Therapies:|

|First Choice: Black cohosh (Isopropanolic Extract) 40 mg/day|

|Alternatives|

|Isoflavones: Genistein (≥ 15 mg/day)|

|Sage: 300-400 mg/day|

|Hops: 100 µg of 8-PN (8-prenylnaringenin)|

|Pollen Extract: 160 mg/day|

|• Reevaluate after 12 weeks using the Cervantes Short form scale|

|4. Moderate-Severe Symptoms Management|

|• Assess eligibility for hormone replacement therapy (HRT) or fezoli-|

|netant 45 mg|

|• Follow criteria for HRT use (refer to the "Criterios de elegibilidad|

|para el uso de la THM")|

|• If Menopausal domain > 25 (Moderate-severe)|

|[175]||blind and|• Venlafaxine (75 mg/day)|clonidine than venlafaxine (the latter|taste and loss of appetite.|

|||crossover|Women with BC treated with|more immediate effect)||

||||antiestrogens, aromatase|||

||||inhibitors or LHRH analogues|||

|[176]||blind|• Venlafaxine (75 mg/day)|treatment of VMS. (clonidine at the end|(greater in the venlafaxine group)|

||||• PCB|of treatment; venlafaxine more||

||||Women with BC|immediately -first weeks of treatment-)||

|DRUG|VMS REDUCTION|ADDITIONAL BENEFIT|ADVERSE EFFECTS| |---|---|---|---|

|SELECTIVE SEROTONIN REUPTAKE||||

|INHIBITORS||||

||(14-38 %)|function||

||(23 %)|libido||

||(30 %)|vasomotor disorders||

|||Does not affect sexual function||

|Fluoxetine (20 mg/day)|50 % vs PCB (36 %)|Improves HRQoL and mood||

|||Does not affect libido||

|SSRI-SNRI||||

|release|(27 %)||function|

|||Does not affect sexual function|week of treatment.|

|ANTICONVULSANTS||||

|with 300 mg/day)||||

|Pregabalin (150-300 mg) divided doses|65-71 % vs PCB|||

||(50 %)|||

|'''||||

||||constipation.|

Funding

Healthy living habits, alternative therapies, and VMS.

(continued )

[94][95] [96]tudies including retrospective and prospective cohort studies, prospective and retrospective case-control studies, and cross-sectional designs Natural products and VMS.been proven to alleviate VMS.The recommended dosage of the extract is 300-400 mg/day.[92,93] .3.2.5 Cytoplasmic pollen extract is a safe and effective non-hormonal option for treating VMS.It also improves other HRQoL parameters.The recommended dose is 160 mg/day for the first two months, followed by 80 mg/day[94][95] [96].

Hormonal replacement therapy and VMS.

Neurokinin inhibitors and VMS.

Medications for relieving VMS.

For both mild and moderate-severe cases, perform a follow-up assessment 12 weeks after starting the intervention • Use the Cervantes Short form scale to evaluate the effectiveness of the treatment6.Next Steps Based on Follow-up• If symptoms improve, continue the current management • If no improvement, reassess and consider alternative or additional treatments

(continued ) : Vasomotor symptoms; HF: Hot flushes; SR: Systematic review; RCT: Randomized control tried; PCB: placebo; MT: Metanalysis; BC: Breast cancer; BP: Blood pressure; PS: Prospective study; PS: Prospective randomized study; TSD: Transdermal; HRT: Hormonal therapy; ECE: Equine conjugated estrogens; E2: estrogens; Ca: Calcium; HRQoL: Health-related quality of life.

EN_PAPER

Management of menopausal hot flushes. Recommendations from the Spanish Menopause Society

Authors

We used the references obtained from the database review to create a search strategy tailored to the requirements of each database. This strategy involved using a combination of search terms related to each clinical question defined by the group of experts. We, initially screened the titles, abstracts, and study types, following specific inclusion and exclusion criteria. After that, we evaluated the selected studies more thoroughly and prepared summary tables with the most relevant data for each clinical question. Once these tables were completed, the review team shared them and performed a narrative synthesis and analysis of the evidence for each clinical question to issue corresponding grades of recommendation.

Inclusion criteria: The publication should present information on the experience of women suffering from VMS, the HRQoL of these women, and validated Quality of Life (QoL) scales to measure VMS. The publication should present information on treatments for VMS included in systematic reviews (SR), meta-analyses (MT), randomized clinical trials (RCTs), and observational studies (OE) (case-control studies (CCE); prospective and retrospective cohort studies (PCS-RCS) that include a control group without treatment.

Exclusion Criteria: Studies that do not involve peri-postmenopausal subjects. Studies conducted on animals or in vitro. Editorials, notes, comments, letters, opinion articles, and summaries of conference communications. Studies that do not provide information about VMS, treatments for VMS, women's experiences, and HRQoL. Studies not published in Spanish or English.

Abstract

This project aims to develop recommendations for treating vasomotor symptoms (VMS) based on the Cervantes short-form scale score (menopausal domain) using the best available evidence. A total of 166 studies were selected: 108 randomized controlled trials, 23 systematic reviews, 3 reviews, 3 meta-analyses, 11 case-control studies, 9 observational studies, and 12 transversal studies. To achieve this objective, a series of PICO (Patient, Intervention, Comparison, and Outcome) questions have been established for the treatment of VMS. We evaluate the quality of the scientific evidence and, with the findings, create a decision framework to treat hot flashes based on the Cervantes short-form scale score.

1. Introduction

Vasomotor symptoms (VMS) are common during menopause and are the main reason women seek medical advice at this stage of life. They are also the most characteristic symptom of climacteric syndrome. The frequency and severity of VMS vary, but they can lead to sleep disturbances, fatigue, anxiety, and irritability. This, in turn, affects their health-related quality of life (HRQoL) making it challenging to maintain normal routines and enjoy daily activities. Effective management of VMS is crucial for improving the HRQoL during menopause [1, 2] . To support healthcare professionals involved in women´s health care (not for women) we have developed the Spanish guideline for hot flushes.

We created a series of PICO (Patient, Intervention, Comparison, and Outcome) questions for each significant VMS treatment. We then assessed the quality of the scientific evidence and used our findings to develop a treatment decision framework for hot flushes based on the Cervantes Scale Short Form (C-SF).

2. Methods

2.1. Bibliographic review

We conducted thorough literature searches, covering research from the past 20 years in the following databases: PubMed®/MEDLINE (NCBI), ScienceDirect (Elsevier), and Cochrane Library (Wiley Online). We developed a tailored search strategy for each database, using a combination of controlled vocabulary and search terms related to hot flushes. These terms included (Climacteric [MeSH Terms]), (climacterics [MeSH Terms] ), (menopause [MeSH Terms]), (menopause, premature [MeSH Terms] ), (post-menopause [MeSH Terms]), (post menopauses [MeSH Terms] ), and (pre-menopause [MeSH Terms]); ("Hot Flashes/diagnosis"[Mesh] OR "Hot Flashes/diet therapy" [Mesh] OR "Hot Flashes/drug therapy"[Mesh]; MeSH descriptor: [Hot Flashes] explode all trees and with a qualifier(s): [therapy -TH, epidemiology -EP, etiology -ET, diagnosis -DI, diet therapy-DT]. We also used validated filters as necessary to retrieve the appropriate study designs. (Flowchart 1)

2.2. Inclusion and exclusion criteria

The search was conducted openly to identify all publications in Spanish and English related to VMS during peri-post menopause over the last 20 years. The objective was to identify publications with relevant information about the treatment of VMS, the experience, and Health-Related Quality of Life (HRQoL) of women in peri or post menopause who report VMS, and the available treatments. In the review we do not include articles in women with ovarian insufficiency that suffer VMS because the position statement about the treatment in this woman is HRT with or without VMS.

2.3. Data extraction

After confirming that the publications met at least one of the inclusions and none of the exclusion criteria, we extracted relevant information in a standardized manner. To accomplish this, we prepared to compile the appropriate information from the selected articles for review.

2.4. PICO development questions

The review team has outlined five PICO questions to address the following clinical and research queries:

1. Should healthy lifestyle habits be recommended for postmenopausal women for treating VMS? 2. Should natural therapies be used in postmenopausal women for treating VMS? 3. Should menopausal hormone therapy (HRT) be used in postmenopausal women for treating VMS? 4. Should neurokinin antagonists be used in postmenopausal women for treating VMS? 5. Should non-hormonal drugs be used in postmenopausal women for treating VMS?

2.5. Quality of evidence and Grade of recommendation [3] All decisions were made based on the level of evidence from the type of study, with an additional vote from the expert group that developed the guideline.

The quality of evidence was defined as follows: HIGH: It is very unlikely that new research will alter our confidence in the effect estimate; MODERATE: New studies are likely to have a significant impact on our confidence in the effect estimate and may modify this estimate;

LOW: New studies are very likely to have a significant impact on our confidence in the effect estimate, and this estimate is likely to be modified;

VERY LOW: Any effect estimate is highly uncertain.

The types of studies used to establish the grade of recommendation were as follows: Meta-analysis, Systematic Reviews, Randomized Clinical Trials: High quality evidence-Strong recommendation for or against; Cohort or Case-Control Studies: Moderate or low-quality evidence-Weak recommendation for or against; Non-Analytical Studies, Case Series: Low or very low-quality evidence-Weak recommendation for or against.

2.6. Instruments to measure HRQoL

Among the most important HRQoL scales are the Blatt-Kupperman Index [4] , the Women Health Questionnaire (WHQ) [5] , the MENCAV questionnaire [6] , the Menopause Rating Scale (MRS) [7] , the Menopause Quality of Life (MENQOL) [8] , the Utian Quality of Life Score (UQOL) [9] , the Greene Climacteric Scale [10] , the Cervantes Scale (CS) [11] and the Cervantes Scale in its short version (C-SF) [12] [13] [14] [15] [16] . The C-SF has been used to establish the decision algorithms in this Spanish guide.

2.6.1. Cervantes scale short form (C-SF)

The CS is a specific HRQoL questionnaire that was originally developed in Spanish to be used in Spain for women through and beyond menopause. The CS can be reduced to a 16-item abridged version (C-SF) that maintains the original dimensional structure and psychometric properties [14] . This abridged questionnaire has four main dimensions: Menopause and Health (VMS, Health, and Aging), Psychology, Sexuality, and Relationship. The questionnaire is scored from 0 to 100, with 0 indicating no impact from menopause symptoms and 100 indicating the greatest possible impact. The C-SF has been used to establish There is a positive relationship between the intake of caffeinated soft drinks and the frequency and severity of VMS.

STRONG IN FAVOR

(continued on next page)

Smith RL et al. [41] 761 TS Using data from 761 women aged 45-54 years of age at baseline followed for 1-7 years.

Ex-smoking women have a lower risk of suffering from VMS than those who continue smoking, but a higher risk than those who have never smoked. Women who had been smokers for more than 5 years had a lower probability of VMS than those who continued smoking or had quit in the previous 5 years. decision algorithms in this Spanish guide [13] .This scale has been used because it is validated and compared with other scales [12] [13] [14] [15] [16] . There are no other short and easy-to-use scales in routine clinical practice that have a quantifiable vasomotor domain by score and with cutoff points established through population curves that allow distinguishing those women whose vasomotor symptoms affect their HRQoL. Research has shown that the questionnaire is sensitive to changes in the HRQoL for women after menopause, especially related to treatments for menopause symptoms. It shows that a score of more than 25 points in the Menopause and Health domain has a sensitivity and specificity greater than 80 % in identifying women with moderate to severe VMS who require pharmacological treatment. A change of 6.7 points in the total score indicates a significant increase in disability for work and daily activities, greater economic loss, fewer years of disability-free life, fewer hours of peaceful sleep, and more doctor visits per year due to menopause symptoms. This makes successive scores on the C-SF useful for monitoring treatment effectiveness. The C-SF scale also has predictive value in response to treatment, as it can predict significant improvement in a woman's quality of life when a specific type of treatment is prescribed, based on the initial score. The Statement encourages the establishment of a treatment regimen based on the initial C-SF scores and recommends monitoring the response to treatment with successive C-SF assessments at intervals of no less than three months [15, 16] .To access the Cervantes SF scale score go to https://aeem.es/calculadora-escala-cervantes-decalidad-de-vida/.

2.7. Guideline development steps

This structure outlines the development process of the Statement, from assembling the development group to finalizing the document with a comprehensive review.

1. Integration of the Development Group

o Assemble a multidisciplinary team of experts to guide the development of the Statement.

2. Definition of the General Statement Framework

o Establish the overall structure, goals, and scope of the Statement.

3. Results

Recommendations for each PICO question based on evidence:

3.1. Should healthy lifestyle habits be recommended in postmenopausal women for treating VMS? (Table 1 )

3.1.

1 Exercise and Healthy Lifestyle Habits. The evidence regarding the use of exercise as a treatment for VMS in menopause is inconclusive. However, due to the additional benefits exercise provides, it is recommended during this stage of life [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] .

3.1.2 Mediterranean-Style Diet: A Mediterranean-style diet that includes weight control has a beneficial effect on VMS [27] [28] [29] [30] .

3.1.3 Reduction of Tobacco, Alcohol, and Caffeine Consumption:

There is a strong correlation between tobacco consumption, alcohol consumption, caffeine consumption, and the occurrence of VMS in postmenopausal women. Reducing the consumption of these substances is advisable to prevent the onset or worsening of VMS [31] [32] [33] [34] [35] [36] [37] [38] [39] [40] [41] [42] [43] .

3.1.4 Cognitive behavioral therapy (CBT) shows a reduction in vasomotor symptoms, myalgia, anxiety, and depression, thereby increasing the quality of life [44] [45] [46] [47] [48] 3.1.5 Hypnosis has consistently shown clinically significant reduction in VMS. However, its use in clinical practice is limited by the lack of accessibility to trained professionals [49, 50] .

3.1.6 There is insufficient evidence to recommend acupuncture or yoga to treat VMS [51] [52] [53] [54] [55] [56] [57] [58] .

3.1.7 Although more studies are needed, it is recommended to maintain an adequate weight, avoid smoking, and practice regular exercise to alleviate VMS 2) 3.2.1 Given that the benefits outweigh the risks and are accompanied by a good safety profile in estrogen-sensitive tissues, without side effects, black cohosh can be recommended in the treatment of VMS. It can be safely used in women with natural menopause and in patients with estrogen-dependent tumors who have VMS [59] [60] [61] [62] [63] .

3.2. Should natural products be used in postmenopausal women for treating VMS? (Table

3.2.2 The available evidence regarding the use of soy dietary supplements and red clover extracts for the treatment of VMS is contradictory. However, use of soy preparations standardized to contain at least 15 mg/day of genistein is recommended

3.3. Should HRT be used in postmenopausal women for treating VMS? (Table 3)

3.3.1. Both transdermal and oral HRT routes are effective in treating VMS and are better than a placebo [97] [98] [99] [100] [101] . The current recommendation is to start with lower doses, such as 0.025 mg of transdermal estradiol or 0.5 mg/day of oral estradiol, and increase as needed to relieve symptoms [102] [103] [104] .

3.3.2. Oral HRT leads to a more favorable bleeding pattern than transdermal HRT [105] [106] [107] [108] .

3.3.3. Oral micronized progesterone (MPG) with estradiol, estradiol with norethisterone acetate (NETA), and estradiol with Levonorgestrel intrauterine device (LNG-IUD) have better rates of amenorrhea compared to other formulations [109] [110] [111] .

3.3.4 The patient profile for LNG-IUD plus natural estrogen typically includes perimenopausal women with heavy bleeding, VMS, and the need for contraception [112] [113] [114] [115] [116] [117] .

3.3.5 To minimize the risk of thrombosis, it is recommended to use transdermal HRT, estradiol plus NETA, or estradiol plus oral MPG [118] [119] [120] .

3.3.6 Tibolone could be an alternative for women experiencing breast tenderness caused by classic HRT [121, 122] .

3.3.7. Tissue Selective Estrogen Complex (TSEC) could also be an alternative for women with breast tenderness caused by classic HRT and severe osteopenia/osteoporosis [123] .

3.3.8. The use of 300 mg of oral MPG shows improvement in VMS compared to placebo [124, 125] .

3.3.9. Therapies composed of bioidentical hormones are currently not regulated and do not comply with safety standards set by the FDA (Food and Drug Administration), EMA (European Medicines Agency), or AEMPS (Spanish Agency for Medicines and Medical Devices). Therefore, their use is not recommended [126] . 3.3.10. Reviewing the literature, there is not a minimum period, HRT is given to treat symptoms and should be stopped when symptoms are no longer evident. Furthermore there is agreement that HRT should be started before 60 years old or < 10 years since entering menopause (generally before is better, "window of opportunity"), but there is not an established maximum period after which it must be stopped. Generally, a decreased dose can be given or another route of administration considered for older women who have already started HRT during the correct frame.

3.3.11. Both sudden and gradual discontinuations of HRT have been reported, but there is no evidence to suggest that one method is better than the other [127] [128] [129] .

3.3.12. It would be sensible to evaluate patients 12 weeks after starting treatment to assess the effectiveness of HRT, monitor for side effects and, improve adherence [15] . 4) 3.4.1 Fezolinetant 45 mg once daily has shown effectiveness and safety compared to placebo and was well tolerated for treating moderate to severe VMS associated with menopause. Improvement was observed as early as week 1, with continued progress up to week 4, and sustained benefit throughout the 12-week double-blind period. The efficacy was noted to persist over 52 weeks of treatment [130] [131] [132] [133] [134] [135] [136] [137] [138] .

3.4. Should neurokinin antagonists be used in postmenopausal women for treating VMS? (Table

3.4.2. Fezolinetant 45 mg also demonstrated effectiveness versus placebo in reducing sleep disturbances and impairment during the treatment of VMS due to menopause [139] .

3.4.3. Fezolinetant 45 mg is effective in treating moderate-to-severe VMS caused by menopause, regardless of various intrinsic and extrinsic factors [140] .

3.4.4.

A meta-analysis revealed that Fezolinetant 45 mg resulted in a significantly higher proportion of ≥ 75 % responders than Desvenlafaxine 50 mg. Additionally, it was found to be non-inferior to HRT in reducing the frequency of moderate to severe VMS [141] .

3.4.5. The current evidence supporting Elinzanetant is primarily derived from phase 3 clinical trials [142] [143] [144] .

3.4.6. Further research in Phase 4 randomized controlled trials (RCTs) and observational studies (OE) is necessary to validate these emerging therapies' long-term efficacy and safety in real-life settings. 5) 3.5.1. The benefits of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are promising, particularly due to their safety profile. These would be indicated in cases where HRT cannot be used. However, since the absolute benefit is small, costs and the individual woman's preference should guide recommendations. For all drugs, it is recommended to start treatment with the lowest recommended dose, increasing it if necessary, to minimize possible adverse effects. A gradual withdrawal of the drug over 1-2 weeks is advised to avoid potential withdrawal syndromes .

3.5. Should non-hormonal drugs be used in postmenopausal women for treating VMS? (Table

3.5.2 Gabapentin reduces the frequency and severity of VMS compared to placebo [166] [167] [168] [169] [170] [171] [172] [173] [174] .

3.5.3. Clonidine is less effective than venlafaxine in VMS treatment and it has more side effects [175, 176] .

3.5.4. For women with moderate or severe hot VMS that disturb their HRQoL and for whom HRT is not an option, refused, or ineffective, SSRIs and SNRIs such as low-dose paroxetine, venlafaxine, desvenlafaxine, and gabapentin could be used.

Table 6 compares the dosage, effectiveness, and safety of nonhormonal drugs. There are many drugs with VMS as a side effect. You can find more information in the supplementary file in this paper [177] .

4. Discussion

Based on the C-SF scale score, this project aimed to establish criteria for using various therapies in treating VMS. Developing a tool that helps clinicians make decisions using these scales could improve clinical practice. Continuous scores on the C-SF scale could assist in monitoring prescribed treatment and evaluating the woman´s improvement in HRQoL. The C-SF scale has also demonstrated predictive value in treatment response, as it can anticipate a significant improvement in a woman´s HRQoL based on the initial score when a specific treatment is prescribed.

4.1. Strengths

No studies are addressing HRQoL scales to aid clinicians in choosing the best VMS treatment. We anticipate that the widespread use of this decision tool will benefit clinicians treating VMS during menopause.

4.2. Weakness

An important limitation encountered during this project was the extensive use of treatments for VMS during menopause with minimal evidence. This oversight could have led to avoiding products treating VMS with sufficient evidence.

Comparison of the dosage, efficacy, and safety of non-hormonal drugs in hot flushes.

Ethical statement

None

Declaration of Competing Interest

Appendix A. Supporting information

Supplementary data associated with this article can be found in the online version at doi:10.1016/j.eurox.2025.100366.

References

引用 / 出处

2025 SMS建议：更年期潮热的管理. 2025.