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Case example: Barbara is a 52-year-old African American woman who presents with complaints of hot flashes up to 10 times a day and night sweats. She describes waking up 3 to 4 times at night and feels exhausted. She asks you whether there is anything to treat her symptoms. Her last menstrual period was 6 months ago. Medication Formulation Dose (mg) Estrogen Conjugated equine estrogen Oral 0.3, 0.45, 0.625, 0.9, 1.25 (per day) Estradiol* Oral Transdermal patch** 0.025, 0.0375, 0.05, 0.075, 0.1 (1 to 2 times per week Transdermal gel 0.25, 0.5, 0.75, 1.0 (per day) Transdermal spray 1.53 mg per spray (1 to 3 sprays per day) Progestin Medroxyprogesterone acetate Oral 2.5, 5, 10 mg (dosed once a day; can also be dosed for 10 to 15 days a month) Norethindrone acetate Oral (as part of a combination product) Levonorgestrel Patch** (as part of a combination product) Progestin IUD (not FDA approved for postmenopausal women) Micronized progesterone* Oral 100 mg twice a day (may also be dosed at 100 mg or 200 mg daily; can also be dosed for 15 days a month; only FDA approved for cyclic use) *Bioidentical (synthetic hormone that exactly mimics the hormones in the body).
**Patches can be nonadherent.
Abbreviations: IUD, Intrauterine Device; FDA, Food and Drug Administration.
Estrogen Component Progestin Component Oral Conjugated equine estrogen (0.3, 0.45, 0.625 mg) Medroxyprogesterone acetate (1.5, 2.5, 5 mg) Ethinyl estradiol (2.5, 5 mcg) Norethindrone (0.5, 1 mg) 17 Beta Estradiol (0.5, 1 mg) Norethindrone (0.5 mg) 17 Beta Estradiol (0.25, 0.5 mg) Drosperinone (0.5, 1.0 mg) Transdermal 17 Beta estradiol (0.045, 0.05 mcg) Levonorgestrel (0.014, 0.015 mcg) Conjugated equine estrogen (0.45 mg) Bazedoxifene (20 mg)* *Systemic estrogen reuptake inhibitor.
Case cont. Barbara is otherwise healthy. She has no history of HTN, CAD, VTE or breast cancer. She has no family history of breast cancer. You discuss options of hormone therapy and include potential risks and benefits. She elects to start on an estrogen patch and an oral progestin. Case (cont). Barbara’s sister Betty comes to see you for the same complaint as Barbara. Her VMS are quite bothersome, having severe hot flashes up to 10 times a day. Betty was recently diagnosed with hormone receptor positive breast cancer so cannot take systemic hormone therapy. How would you treat Betty? No HT HT Risk of MI 2/1000 3 to 7/1000 (after 1 year of HT use) Risk of VTE 2/1000 4 to 11/1000 (after 1 year of use) Risk of CVA 6/1000 6 to 12/1000 (after 3 years of use) Risk of breast cancer 19/1000 20 to 30/1000 (after 5.6 years of use) *Based on data from 43,637 post-menopausal American women.
**Data may vary based on type of formulation and mode of delivery of HT.
Abbreviations: VTE, Venous Thromboembolism; MI, Myocardial Infarction; CVA, Cerebrovascular Accident
Medication SOR Comments SSRIs36,37 A (Systematic review and meta-analysis) · Paroxetine is the only nonhormonal medication approved by the FDA for hot flashes.
· Paroxetine should not be used in people taking tamoxifen
· Systematic review suggests that escitalopram is superior to other SSRIs36
· Another systematic review documented the benefit of escitalopram, paroxetine, and fluoxetine over other SSRIs40
· May be limited by side effects
SNRIs40 A (systematic review and meta-analysis) · Good evidence for the benefit of venlafaxine and desvenlafaxine. Not enough studies to evaluate benefit of duloxetine.40,44
Fezolinetant41 (Neurokinin receptor antagonist) A (systematic review and meta-analysis) Fair evidence for benefit over placebo. Most studies were small but showed no significant adverse effects. Gabapentin38 A (systematic review) · Good evidence for gabapentin, but not enough studies on pregabalin.35,38
· May be limited by side effects
· Effective dose not clear
Clonidine34,35 B (randomized controlled trials) · Limited by side effects
Abbreviations: SSRIs, Selective Serotonin Reuptake Inhibitors; SNRIs, Serotonin-Norepinephrine Reuptake Inhibitors; FDA, Food and Drug Administration
Intervention Efficacy Precautions Notes Black Cohosh
Cimicifuga acemosePossibly effective49,50,51 Rare but potential liver toxicity; consider monitoring liver enzymes or avoiding in liver disease; Estrogen receptor stimulation seems unlikely,52,53 but not definitively safe in high risk hormone responsive cancers Common dose is 20-40 mg twice daily of a standardized extract;
Possible SERM-like activity; also thought to have anti-inflammatory and SSRI activity leading to potential to also help with aches/pains and mood related to perimenopause54Soy
Glycine maxPossibly effective59,60 Phytoestrogen Products that contain at 15 mg-30 mg of the soy isoflavone genistein more consistently effective61;
Genistein content in foods:
½ c miso—32 mg
3 oz uncooked tempeh: 30.7 mg
3 oz cooked tempeh: 18 mg
1 oz dry roasted soybeans: 21.2 mg
3 oz soft tofu: 10.1 mg
½ cup edamame: 6.3 mg
1 cup low fat soy milk: 3.7mg62Siberian Rhubarb
Rheum rhaponticumPossibly effective55 Use root; leaf can be toxic
May activate estrogen receptor beta, but not alphaStudied dose is 4 mg of a dried extract, once daily.
May also help with anxiety, sleep, mood, quality of life, fatigueSage
Salvia officinalisPossibly effective56,57 Recognized as a food
In very high doses may be toxic due to thujone constituent58; alcohol extracts have higher thujone content than water infusions (tea);
Possibly weak estrogen activityConsider 1tsp of dried sage 2 to 3 x daily steeped in 1 cup near-boiling water for 7 to 10 minutes then strained Red Clover
Trifolium pratenseInsufficient reliable evidence63,64 Phytoestrogen 80 mg of dried leaves and 80 mg of standardized extract have both been studied Yoga Possibly effective65,66 Caution in patients with hypermobility syndromes or osteoporosis May also help with psychological symptoms; practices that include meditation and breathwork may be better than hot yoga Acupuncture Insufficient reliable evidence67,68 Improves VMS over no treatment, but not over sham acupuncture (debate over “sham” acupuncture as true control is problematic in acupuncture literature in general)
May be an appropriate adjunct to improve overall quality of lifeHypnosis Likely effective69 Use with caution or avoid in those with history of trauma or abuse and with active psychosis Professionals trained in clinical hypnosis can be found at: Available at: https://www.asch.net/aws/ASCH/pt/sp/find-member Mindfulness, CBT, behavior therapies Possibly effective70,71 Therapies may decrease negative experience or interference of hot flashes but not necessarily frequency. A specific protocol CBT for menopausal symptoms (CBT-Meno) may be more efficacious (study compared to waitlist). Abbreviations: SERM, Selective Estrogen Receptor Modulator; SSRI, Selective Serotonin Reuptake Inhibitor; VMS, Vasomotor Symptoms; CBT, Cognitive Behavioral Therapy.
SORT Estrogen containing hormone therapy is the most effective treatment for vasomotor symptoms (VMS). A Paroxetine and fezolinetant are the only FDA approved nonhormonal medications for the treatment of VMS and are better than placebo A Shared Decision Making that considers the benefits and risks of further hormone therapy should be utilized when considering discontinuation of hormone therapy for treatment of VMS. C SSRIs, SNRIs, and gabapentin are effective therapies for VMS. A Abbreviations: SSRI, Selective Serotonin Reuptake Inhibitor; VMS, Vasomotor Symptoms; SNRI, Serotonin-Norepinephrine Reuptake Inhibitor; FDA, Food and Drug Administration
Case (cont.): Betty decides to start with some integrative approaches to treat her vasomotor symptoms. She starts with CBT and hypnosis and adds black cohosh. You discuss the use of an SSRI (other than paroxetine since she is on tamoxifen) if these interventions do not help with her symptoms.
Betty comes back to see you 3 months later and reports that CBT, hypnosis and black cohosh have been partially effective for her VMS, but she is still not sleeping well and has increased anxiety. You start her on venlafaxine and suggest that she discontinue black cohosh, but continue with CBT and hypnosis. You see her back in 2 months and she states that the venlafaxine is working very well. You continue on the same dose and schedule a follow up in 6 months.
