Treatment options for vasomotor symptoms in menopause: focus on desvenlafaxine

Figures & data

Table 1 Nonpharmacologic treatments for vasomotor symptoms (VMS)^12–18

Nonpharmacologic treatment	Evidence
Acupuncture	A randomized clinical trial illustrated that acupuncture was as effective as venlafaxine at reducing hot flushes.^Citation12 Another study and review have shown a significant reduction in the mean number of hot flushes with acupuncture compared to placebo.^Citation13,Citation14
Hypnosis	Two small studies in breast cancer patients showed that hypnosis was more effective at reducing vasomotor symptoms (VMS) compared to no treatment.^Citation15,Citation16
Lifestyle changes Layered clothing Cool atmosphere Cool drinks Avoiding hot/spicy food Exercise/weight loss Smoking cessation	Studies have shown that keeping cool by using layered clothing, cooler room temperatures, drinking cool liquids, and avoiding triggers such as hot/spicy food can help with the severity of hot flushes.^Citation17 Studies regarding the efficacy of exercise in relieving VMS are ongoing;^Citation18 however, at this time there is an overall lack of randomized controlled clinical trials. Clinical trials evaluating the effect of weight loss on VMS are lacking. Many researchers believe smoking cessation can help reduce vasomotor symptoms, although evidence in this area is lacking, as there are currently no clinical trials evaluating this idea.

Table 2 Herbals and vitamins for the treatment of vasomotor symptoms (VMS)^20–35

Herbal/vitamin	Efficacy/safety information
Black cohosh	Two meta-analyses showed black cohosh to have some benefit in treating VMS.^Citation20,Citation21 One randomized trial showed black cohosh to have similar efficacy to tibolone at reducing VMS, as measured by the Kupperman Menopause Index.^Citation22 One meta-analysis and another randomized controlled trial have shown no benefit to treatment with black cohosh.^Citation22,Citation24 Long-term effects are unknown, and there exists a possibility of hepatotoxicity.^Citation20,Citation21 However, a recent meta-analysis of five studies (two had a duration of 12 weeks, two had a duration of 16 weeks, and one had a duration of 24 weeks) showed that black cohosh does not negatively impact liver function.^Citation25 The overall long-term efficacy and safety data for black cohosh remain unclear.
Black cohosh with St John’s wort	A randomized controlled trial showed that the combination of these herbals significantly improved VMS and symptoms of depression as measured by the Menopause Rating Scale and Hamilton Depression Rating Scale, respectively, compared with placebo.^Citation26
Dehydroepiandrosterone (DHEA)	A small study has shown a reduction in the frequency of hot flushes in patients taking DHEA supplements.^Citation27 Larger randomized trials are needed to further evaluate these findings.
Evening primrose oil	Randomized trials have not shown any benefit in the frequency of hot flushes with evening primrose oil.^Citation28
Phytoestrogens Isoflavones Soy Red clover Lignan	One clinical trial and two meta-analyses do not support the use of soy for vasomotor symptoms.^Citation29^–^Citation31 A very recent meta-analysis of 17 trials found soy isoflavone supplements to be significantly more effective than placebo at reducing the frequency and severity of hot flashes.^Citation32 A recent meta-analysis and randomized clinical trial concluded there was no impact on the incidence and severity of hot flushes with red clover.^Citation30,Citation33 Flaxseed, which is very high in lignan, has been studied for the treatment of hot flushes and has been shown to successfully reduce VMS.^Citation34
Vitamin E	A randomized clinical trial showed that Vitamin E reduced the occurrence of hot flashes by about one per day;^Citation35 however, it was not preferred by patients over placebo. Not recommended at this time due to clinically insignificant effects.

Table 3 Clinical trials focusing on the efficacy of desvenlafaxine in vasomotor symptoms^62–65

Clinical trial	Trial design	Primary and secondary outcomes	Primary results	Secondary results
Speroff et al^Citation62	52-week, multicenter, randomized, double-blind, placebo-controlled trial n = 707 postmenopausal women 620 women included in modified ITT analysis Treatment groups (assigned in a 2:2:2:2:1 ratio): – Desvenlafaxine 50, 100, 150, or 200 mg/day – Placebo No dose-titration used	Change from baseline in daily number of moderate-to-severe hot flashes compared with placebo at weeks 4 and 12 Change from baseline in average daily hot flash severity score compared with placebo at weeks 4 and 12 Proportion of women achieving at least a 50% or 75% reduction from baseline in number of hot flashes at weeks 4 and 12 Change from baseline in daily number of nighttime awakenings due to hot flashes at weeks 4 and 12	Reductions in average daily number of moderate-to-severe hot flashes from baseline: – Placebo: 51% at week 12 – Desvenlafaxine 50 mg: P = NS vs placebo at weeks 4 and 12 – Desvenlafaxine 100 mg: 64% at week 12 (P = 0.005 vs placebo at week 12; P = 0.013 vs placebo at week 4) – Desvenlafaxine 150 mg: 60% at week 12 (P = 0.02 vs placebo at week 12; P = NS vs placebo at week 4) – Desvenlafaxine 200 mg: P = NS vs placebo at weeks 4 and 12 Moderate-to-severe reductions in average daily hot-flash severity score – Placebo: 18% at week 12 – Desvenlafaxine 50 mg: P = NS vs placebo at weeks 4 and 12 – Desvenlafaxine 100 mg: 31% at week 12 (P = 0.002 vs placebo at week 12; P = NS vs placebo at week 4) – Desvenlafaxine 150 mg: P = NS vs placebo at weeks 4 and 12 – Desvenlafaxine 200 mg: 27% at week 12 (P = 0.013 vs placebo at week 12; P = NS vs placebo at week 4)	Proportion of patients achieving at least a 75% reduction from baseline in number of hot flashes (results for the 50% reduction were not reported) – Placebo: 18.2% at week 4, 28.6% at week 12 – Desvenlafaxine 50 mg: P = NS vs placebo at weeks 4 and 12 – Desvenlafaxine 100 mg: 36.6% (P = 0.005) vs placebo at week 4; 49.7% (P = 0.003) vs placebo at week 12 – Desvenlafaxine 150 mg: 38% (P = 0.003) vs placebo at week 4; P = NS vs placebo at week 12 – Desvenlafaxine 200 mg: 33.3% (P = 0.021) vs placebo at week 4; 45% (P = 0.022) vs placebo at week 12 Reductions in the daily number of nighttime awakenings versus placebo at week 12 (results from week 4 were not reported) – Placebo: −2.21 – Desvenlafaxine 50 mg: −2.30 (P = NS) – Desvenlafaxine 100 mg: −2.77 (P = 0.013) – Desvenlafaxine 150 mg: −2.69 (P = 0.034) – Desvenlafaxine 200 mg: −2.68 (P = 0.043)
Archer et al^Citation63	26-week, double-blind, placebo-controlled trial n = 567 post-menopausal women 484 women included in modified ITT analysis Treatment groups: – Desvenlafaxine 100 or 150 mg/day – Placebo No dose titration used	Change from baseline in average daily number of moderate-to-severe hot flashes compared with placebo at weeks 4 and 12 Change from baseline in average daily hot-flash severity score compared with placebo at weeks 4 and 12 Reduction in number of moderate and severe hot flashes of at least 50% and 75% from baseline compared to placebo Change from baseline in the number of nighttime awakenings due to hot flashes compared to placebo at weeks 4 and 12	Reductions in average daily number of moderate-to-severe hot flashes from baseline: – Placebo: 47% at week 12 – Desvenlafaxine 100 mg: 60% at week 12 (P < 0.002 vs placebo at week 4; P < 0.001 at week 12) – Desvenlafaxine 150 mg: 66% at week 12 (P < 0.002 vs placebo at week 4; P < 0.001 at week 12) Reductions in average daily hot-flash severity score at week 12: – Placebo: 13% – Desvenlafaxine 100 mg: 24% (P < 0.001 vs placebo) – Desvenlafaxine 150 mg: 29% (P < 0.001 vs placebo) Reduction in the average hot flash severity score was significant at week 4 in both desvenlafaxine 100-mg and 150-mg groups (P < 0.005 for both comparisons; actual percentages not given)	Significantly greater percentage of women in desvenlafaxine 100-mg and 150-mg groups had at least a 50% and 75% reduction in number of moderate and severe hot flashes compared to placebo group at weeks 4 and 12 (P ≤ 0.004 for all comparisons; actual percentages not given) Reductions in the daily number of nighttime awakenings versus placebo at week 4 were significant for both desvenlafaxine groups (P < 0.026; actual reductions not given) Reductions in the daily number of nighttime awakenings versus placebo at week 12 – Placebo: 3.2–1.8 – Desvenlafaxine 100 mg: 3.9 to 1.5 (P < 0.026) – Desvenlafaxine 150 mg: 3.5 to 1.1 (P < 0.001)
Archer et al^Citation64	12-week, double-blind, placebo-controlled trial n = 458 postmenopausal women 452 included in the modified ITT analysis Treatment groups: – Desvenlafaxine 100 or 150 mg/day – Placebo Dose titration used	Change from baseline in average daily number of moderate-to-severe hot flashes compared to placebo at weeks 4 and 12 Change from baseline in average daily hot-flash severity score compared with placebo at weeks 4 and 12 Reduction in number of moderate and severe hot flashes of at least 50% and 75% from baseline Change from baseline in number of nighttime awakenings attributed to hot flashes at weeks 4 and 12	Reductions in average daily number of moderate-to-severe hot flashes from baseline versus placebo: – Placebo: 50.8% at week 12 – Desvenlafaxine 100 mg: no percentage given at week 4 (P < 0.012); 65.4% at week 12 (P < 0.005) – Desvenlafaxine 150 mg: no percentage given at week 4 (P < 0.012); 66.6% at week 12 (P < 0.012) Average daily hot-flash severity scores were reduced significantly from baseline for both desvenlafaxine groups compared with placebo at weeks 4 and 12 (P < 0.001 for all comparisons)	Significantly greater percentage of women in desvenlafaxine 100-mg and 150-mg groups had at least a 50% and 75% reduction in number of moderate and severe hot flashes compared to placebo group at weeks 4 and 12 (P < 0.001 for all comparisons) Desvenlafaxine 100 mg or 150 mg significantly reduced the average daily number of nighttime awakenings compared to placebo at weeks 4 and 12 (P ≤ 0.048 for all comparisons) – Placebo: 3.2–2.0 at week 4; 1.8 at week 12 – Desvenlafaxine 100 mg: 3.3–1.5 at week 4; 1.3 at week 12 – Desvenlafaxine 150 mg: 3.1–1.5 at week 4; 1.3 at week 12
Bouchard et al^Citation65	12-week, multicenter, randomized, double-blind, placebo- and active-controlled trial n = 485 postmenopausal women 451 women included in modified ITT analysis Treatment groups: – Desvenlafaxine 100 mg/day – Tibolone 2.5 mg/day – Placebo	Change from baseline in average daily number of moderate and severe hot flashes compared to placebo at weeks 4 and 12 Reduction in the average daily severity of hot flashes at weeks 4 and 12 Percentage of women achieving response (defined as 50% and 75% reductions from baseline in the number of moderate and severe hot flushes at week 12)	Reductions in average daily number of moderate and severe hot flashes from baseline: – Placebo: 57.5% at week 12 – Desvenlafaxine: 57.7% at week 12 (P = NS vs placebo at weeks 4 and 12) – Tibolone: 81% at week 12 (P < 0.001 vs placebo at weeks 4 and 12) Average daily hot flush severity score was not significantly reduced for desvenlafaxine group at weeks 4 and 12 compared to the placebo group, but it was significant for tibolone group at weeks 4 and 12 vs placebo (P < 0.001 for both comparisons)	Proportion of patients achieving at least a 50% or 75% reduction from baseline in number of hot flashes – Desvenlafaxine: P = NS at weeks 4 and 12 – Tibolone: P < 0.001 at weeks 4 and 12

Abbreviations: ITT, intention-to-treat; NS, not significant.

WalkerEMRodriquezAIKohnBAcupuncture versus venlafaxine for management of vasomotor symptoms in patients with hormone receptor positive breast cancer: a randomized, clinical trialJ Clin Oncol201028463464020038728

 PubMed Web of Science ®Google Scholar

DaleyAMacArthurCMutrieNExercise for vasomotor menopausal symptomsCochrane Database Syst Rev20074CD00610817943886

 PubMed Web of Science ®Google Scholar

AvisNELegaultCCoeytauxRRA randomized, controlled pilot study of acupuncture treatment for menopausal hot flashesMenopause20081561070107818528313

 PubMed Web of Science ®Google Scholar

ChoSHWhangWWAcupuncture for vasomotor menopausal symptoms: a systematic reviewMenopause20091651065107319424092

 PubMed Web of Science ®Google Scholar

ElkinsGMarcusJStearnsVHasan RajabMPilot evaluation of hypnosis for the treatment of hot flashes in breast cancer survivorsPsychooncology200716548749217048223

 PubMed Web of Science ®Google Scholar

ElkinsGMarcusJStearnsVRandomized trial of a hypnosis intervention for treatment of hot flashes among breast cancer survivorsJ Clin Oncol200826315022502618809612

 PubMed Web of Science ®Google Scholar

The North American Menopause SocietyTreatment of menopause-associated vasomotor symptoms: position statement of the North American Menopause SocietyMenopause2004111113314716179

 PubMed Web of Science ®Google Scholar

KronenbergFFugh-BermanAComplementary and alternative medicine for menopausal symptoms: a review of randomized, controlled trialsAnn Intern Med20021371080581312435217

 PubMed Web of Science ®Google Scholar

BartonDLLoprinziCLQuellaSKProspective evaluation of vitamin E for hot flashes in breast cancer survivorsJ Clin Oncol19981624955009469333

 PubMed Web of Science ®Google Scholar

ShamsTSetiaMSHemmingsRMcCuskerJSewitchMCiampiAEfficacy of black cohosh-containing preparations on menopausal symptoms: a meta-analysisAltern Ther Health Med2010161364420085176

 PubMed Web of Science ®Google Scholar

BaiWHenneicke-von ZepelinHHWangSEfficacy and tolerability of a medicinal product containing an isopropanolic black cohosh extract in Chinese women with menopausal symptoms: a randomized, double blind, parallel-controlled study versus tiboloneMaturitas2007581314117587516

 PubMed Web of Science ®Google Scholar

GellerSEShulmanLPvan BreemenRBSafety and efficacy of black cohosh and red clover for the management of vasomotor symptoms: a randomized controlled trialMenopause20091661156116619609225

 PubMed Web of Science ®Google Scholar

NaserBSchnitkerJMinkinMJde ArribaSGNolteKUOsmersRSuspected black cohosh hepatotoxicity: no evidence by meta-analysis of randomized controlled clinical trials for isopropanolic black cohosh extractMenopause201118436637521228727

 PubMed Web of Science ®Google Scholar

UebelhackRBlohmerJUGraubaumHJBuschRGruenwaldJWerneckeKDBlack cohosh and St John’s wort for climacteric complaints: a randomized trialObstet Gynecol200610724725516449108

 PubMed Web of Science ®Google Scholar

StomatiMMonteleonePCasarosaESix-month oral dehydroepiandrosterone supplementation in early and late postmenopauseGynecol Endocrinol200014534236311109974

 PubMed Web of Science ®Google Scholar

ChenoyRHussainSTayobYO’BrienPMMossMYMorsePFEffect of oral gamolenic acid from evening primrose oil on menopausal flushingBMJ199430869275015038136666

 PubMed Web of Science ®Google Scholar

St GermainAPetersonCTRobinsonJGAlekelDLIsoflavone-rich or isoflavone-poor soy protein does not reduce menopausal symptoms during 24 weeks of treatmentMenopause200181172611201510

 PubMed Web of Science ®Google Scholar

KrebsEEEnsrudKEMacDonaldRWiltTJPhytoestrogens for treatment of menopausal symptoms: a systematic reviewObstet Gynecol2004104482483615458907

 PubMed Web of Science ®Google Scholar

TakuKMelbyMKKronenbergFKurzerMSMessinaMExtracted or synthesized soybean isoflavones reduce menopausal hot flash frequency and severity: systematic review and meta-analysis of randomized controlled trialsMenopause3192012 [Epub before print.]

 Web of Science ®Google Scholar

NelsonHDVescoKKHaneyENonhormonal therapies for menopausal hot flashes: systematic review and meta-analysisJAMA2006295172057207116670414

 PubMed Web of Science ®Google Scholar

TiceJAEttingerBEnsrudKWallaceRBlackwellTCummingsSRPhytoestrogen supplements for the treatment of hot flashes: the Isoflavone Clover Extract (ICE) Study: a randomized controlled trialJAMA2003290220721412851275

 PubMed Web of Science ®Google Scholar

LewisJENickellLAThompsonLUSzalaiJPKissAHilditchJRA randomized controlled trial of the effect of dietary soy and flaxseed muffins on quality of life and hot flashes during menopauseMenopause200613463164216837885

 PubMed Web of Science ®Google Scholar

SperoffLGassMConstantineGOlivierSEfficacy and tolerability of desvenlafaxine succinate treatment for menopausal vasomotor symptoms: a randomized controlled trialObstet Gynecol20081111778718165395

 PubMed Web of Science ®Google Scholar

BouchardPPanayNde VilliersTJRandomized placebo- and active-controlled study of desvenlafaxine for menopausal vasomotor symptomsClimacteric2012151122022066790

 PubMed Web of Science ®Google Scholar

ArcherDFDupontCMConstantineGDPickarJHOlivierSDesvenlafaxine for the treatment of vasomotor symptoms associated with menopause: a double-blind, randomized, placebo-controlled trial of efficacy and safetyAm J Obstet Gynecol20092003238. e1238. e1019167693

 PubMed Web of Science ®Google Scholar

ArcherDFSeidmanLConstantineGDPickarJHOlivierSA double-blind, randomly assigned, placebo-controlled study of desvenlafaxine efficacy and safety for the treatment of vasomotor symptoms associated with menopauseAm J Obstet Gynecol20092002172. e1172. e1019110224

 PubMed Web of Science ®Google Scholar