Menopause
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Estrogen is by far the most effective treatment for menopausal symptoms.  Unfortunately, especially when combined with progesterone and especially for cigarette smokers, there is an increased risk of cancer and heart disease.  It appears that low dose estrogen by itself with medication free breaks every 2-3 months avoids the side-effects, yet maintains the benefits.  For more, see Estrogen and HRT.

Other treatments are reviewed below for hot flashes, the most common menopausal symptom.

Anti-Depressants: Hot Flashes Treated with Anti-depressants: 165 post-menopausal women DB PC six weeks, 62% drop in the number and severity of hot flashes on paroxetine CR 12.5mg/d vs. 65% with 25mg/d vs. 38% with placebo. Similar reports for fluoxetine and venlafaxine, Wetherhold of GSK. 5/3/03. 165 postmenopausal women experiencing at least two to three hot flashes every day or 14 per week, took either daily placebo or Paxil, at doses of either 12.5 milligrams or 25 milligrams.

Anti-Depressants: Venlafaxine 75 mg Helps Hot Flashes: DB PC 221 pt. Responders 27% with placebo, 37% with 37.5mg/d, 61% with 75mg/d, and 61% with 150mg/d. Side effects dry mouth, nausea, constipation, anorexia. Venlafaxine in management of hot flashes in survivors of breast cancer: a randomized controlled trial. Loprinzi CL, Kugler JW, Sloan JA, Mailliard JA, LaVasseur BI, Barton DL, Novotny PJ, Dakhil SR, Rodger K, Rummans TA, Christensen BJ. Lancet 2000 Dec 16;356(9247):2059-63

Black Cohosh Mild Help Only for More Severe Menopausal Symptoms: In a 12-week DB PC study of 122 menopausal women with >/=3 hot flashes a day, the primary efficacy analysis showed no superiority of the tested black cohosh extract compared to placebo. However, in the subgroup of patients with a Kupperman Index>/=20 a significant superiority regarding this index could be demonstrated (P<0.018). A decrease of 47% and 21% was observed in the black cohosh and placebo group, respectively. The weekly weighted scores of hot flashes (P<0.052) and the Menopause Rating Scale (P<0.009) showed similar results. Prevalence and intensity of the adverse events did not differ in the two treatment groups. Cimicifuga racemosa dried ethanolic extract in menopausal disorders: a double-blind placebo-controlled clinical trial. Frei-Kleiner S, et al. University of Basel, Switzerland. Maturitas. 2005 Aug 16;51(4):397-404.

Black Cohosh and Soy Isoflavones No Benefit for Menopausal Symptoms: In a 12-week DB PC study of 124 postmenopausal women with climacteric symptoms, a combination of soy isoflavones and black cohosh (Actaea racemosa Linnaeus: formerly called Cimicifuga racemosa L.) had no statistically significant benefit over placebo with both groups showing improvement. Effect of a combination of isoflavones and Actaea racemosa Linnaeus on climacteric symptoms in healthy symptomatic perimenopausal women: a 12-week randomized, placebo-controlled, double-blind study. Verhoeven MO, et al. University Medical Center, Amsterdam. Menopause. 2005 Jul-Aug;12(4):412-20

Black Cohosh Didn't Work: In a DB PC study of 85 women, black cohosh did no better than the placebo. J Clin Oncol 2001;19:2739. 

Chamomile Preparation Said to Help Hot Flashes: In a 12-week DB PC study of 55 postmenopausal women with hot flushes and refused hormonal therapy, those given a herbal preparation of chamomille and Angelica sinensis (Climex)(5 chewable tablets daily between meals) had a much larger decrease in number and intensity of hot flushes (90-96% vs 15-25%, p < 0.001) starting in the first month (71% reduction). There was also a marked alleviation of sleep disturbances and fatigue. The immediate effect of natural plant extract, Angelica sinensis and Matricaria chamomilla (Climex) for the treatment of hot flushes during menopause. A preliminary report. Kupfersztain C, et al. Petah Tikva, Israel. Clin Exp Obstet Gynecol. 2003;30(4):203-6. Ed: From past experience, I am skeptic of Israeli herbal research which is sometimes very closely tied to the manufacturer. However, if true, the benefit is impressive.

Clonidine Helps Some: In an 8-week DB PC study of 29 women, clonidine 0.1 mg/day transdermal resulted in a decrease in hot flashes in 12 of 15 women vs. 5 of 14 women on placebo. M. Nagamani et al. Am J Obstet Gynecol 1987;156:561.  Ed: Clonidine is very inexpensive.  It does have a fair rate of side-effects.  It's worth a try, but probably 15% will have to stop it due to side-effects.  This is similar in rate to Prozac and Paxil, although the side-effects are quite different.  It has few drug interactions.

Estrogen Very Effective: Estrogen decreases hot flashes within 4 weeks by 50-100%. A Maclennon et al. Cochrane Database Syst Rev 2004:4:CD002978. For more, see Estrogen.

Fluoxetine (Prozac) Helps Some: In an 8-week DB PC crossover study of of 81 women, fluoxetine decreased hot flashes by 1.5 per day vs. placebo. CL Loprinzi et al. J Clin Oncol 2002;20:1578. Ed: Fluoxetine is a very inexpensive anti-depressant with a moderate rate of side-effects.  It is probably the first non-estrogen choice for side-effects unless the women is on medications whose blood levels will be affected by it. 

Ginkgo: No Benefit for Normal Post-Menopausal Women: In a 6-week DB PC study of 87 women, those receiving gingko 120 mg/day and tested for mental flexibility, planning, memory and sustained attention, and ratings of mood, sleepiness, bodily and menopausal symptoms found that only older women with poorer performance had benefit and only for mental flexibility. Limited cognitive benefits in Stage +2 postmenopausal women after 6 weeks of treatment with Ginkgo biloba. Elsabagh S, Hartley DE, File SE. King's College London, UK. J Psychopharmacol. 2005 Jun;19(2):173-181

Gabapentin Helped a Little: In a 12-week DB PC Study of 59 women, gabapentin 900 mg/day let to a 45% decrease in hot flashes vs. a 29% decrease for placebo. T. Guttuso Jr. et al. Obstet Gyn 2003;101:337. Ed: Gabapentin is expensive with a high rate of side-effects.  It might be a 4th or 5th choice at best.  It's probably not worth the side-effect risk in view of the cost and modest benefit.

Herbal Treatments Not Very Effective:  Eighteen randomized clinical trials have investigated black cohosh (n = 4), red clover (n = 4), kava (n = 3), dong quai (n = 1), evening primrose oil (n = 1), ginseng (n = 1), and combination products (n = 4). Trial quality was generally good, with 16 of 18 studies scoring 3 or more (maximum 5) on the Jadad Scale. Unfortunately, there is no good evidence for any herbal medical product in the treatment of menopausal symptoms. Evidence on black cohosh is promising, but studies have used poor methodology. Univ. Exeter. A systematic review of herbal medicinal products for the treatment of menopausal symptoms. Huntley AL, Ernst E. Menopause. 2003 Sep-Oct;10(5):465-76

Magnolia Bark with Magnesium Reported Helpful: In a DB manufacturer-funded 24-week study of a combination of soy isoflavones (60 mg), lactobacilli (500 millions spores), calcium (141 mg), vitamin D3 (5 microg), Magnolia bark extract (60 mg) and magnesium (50 mg) (Estromineral serena, ES) vs. calcium and D3 alone in 89 menopausal women, flushing, nocturnal sweating, palpitations, insomnia, asthenia, anxiety, mood depression, irritability, vaginal dryness, dyspareunia, and libido loss, significantly decreased in severity and frequency during ES versus Ca+D treatment from the fourth week. Woman wellbeing (good/very good 66.7% vs 20%) judgement on efficacy (72.7% vs 17.1%) and acceptability (93.9% vs 31.4%) were significantly better for ES. Soy isoflavones, lactobacilli, Magnolia bark extract, vitamin D3 and calcium. Controlled clinical study in menopause. Mucci M, et al. Chieti, Italy. . Minerva Ginecol 2006 Aug;58(4):323-34. Ed: Multiple studies show soy without benefit for menopause.

Menopause Research Review: There is still no good evidence that soy foods and isoflavone supplements (from either soy or red clover), black cohosh, or vitamin E help decrease menopausal symptoms; however, no serious side effects have been associated with short-term use of these therapies. Single clinical trials have found no benefit for dong quai, evening primrose oil, ginseng, a Chinese herbal mixture, acupuncture, or magnet therapy. Few data support the efficacy of topical progesterone cream and progesterone has bad long-term side-effects. No clinical trials have been conducted on the use of licorice for hot flashes. The antidepressants venlafaxine, paroxetine, and fluoxetine and the anticonvulsant gabapentin have demonstrated some efficacy for treating hot flashes. Two antihypertensive agents, clonidine and methyldopa, have shown modest efficacy. For moderate to severe hot flashes, systemic estrogen therapy, either alone (ET) or combined with progestogen (EPT) or in the form of estrogen-progestin oral contraceptives, has been shown to significantly reduce hot flash frequency and severity. North American Menopause Society. Menopause. 2004 Jan-Feb;11(1):11-33

Paroxetine CR (Paxil-CR) Helps Some: In a DB PC 6-week trial of 165 women, hot flashes decreased 3.3 per day with 12.5 mg/day and 3.2 with 25 mg/day vs. 1.8 per day decrease with placebo. V. Stearns et al. JAMA 2003;289:2827. Ed: Paxil CR is expensive with with same interaction difficulties as fluoxetine.  It has nothing to say in its favor.

Phytoestrogens Little Benefit: In a review of research, soy products and red clover, which are high in isoflavones, little benefit was found in the studies to date. EE Krebs. Obstet Gyn 2004;104-824. 

Red Clover Isoflavones No Clinically Significant Benefit: In an excellent 3-medical school, large 252-women DB PC 12-week study of two brands of red clover isoflavone extracts containing 82 mg and 57 mg of isoflavones, the reductions in mean daily hot flash count at 12 weeks were virtually identical for the Promensil (5.1), Rimostil (5.4), and placebo (5.0) groups. The Promensil group had an initial decrease in hot flashed slightly faster than the placebo but while the difference was statistically significant, it was not large enough to be clinically significant. UCSF. Phytoestrogen supplements for the treatment of hot flashes: the Isoflavone Clover Extract (ICE) Study: a randomized controlled trial. Tice JA, Ettinger B, Ensrud K, Wallace R, Blackwell T, Cummings SR. JAMA. 2003 Jul 9;290(2):207-14 

Soy Isoflavones and Melatonin Both Ineffective: In a DB PC study of 262 women for 3 months, 80 mg/day of soy isoflavone and 3 mg/day of melatonin both failed to be any better at all than placebo for menopausal symptoms. Milan, Italy. Soy isoflavones and melatonin for the relief of climacteric symptoms: a multicenter, double-blind, randomized study. Secreto G, Chiechi LM, Amadori A, Miceli R, Venturelli E, Valerio T, Marubini E. Maturitas. 2004 Jan 20; 47(1): 11-20

Venlafaxine (Effexor) Helps Some: In a 4 week DB PC study of 221 women with hot flashes, venlafaxine ER at 37.5 mg/d reduced hot flashes by 37%, at 75 mg/d by 61%, and at 150 mg/d by 61% while placebo reduced them by 27%. CL Lopinzi et al. Lancet 2000;356:2059. Ed: Venlafaxine is expensive with a high rate of side-effects and also drug withdrawal problems.  It is at best a 3rd or 4th choice.