Individualized homeopathic treatment and fluoxetine for moderate to severe depression in peri- and postmenopausal women (HOMDEP-MENOP study): a randomized, double-dummy, double-blind, placebo-controlled trial.

BACKGROUND: Perimenopausal period refers to the interval when women's menstrual cycles become irregular and is characterized by an increased risk of depression. Use of homeopathy to treat depression is widespread but there is a lack of clinical trials about its efficacy in depression in peri- and postmenopausal women. The aim of this study was to assess efficacy and safety of individualized homeopathic treatment versus placebo and fluoxetine versus placebo in peri- and postmenopausal women with moderate to severe depression. METHODS/DESIGN: A randomized, placebo-controlled, double-blind, double-dummy, superiority, three-arm trial with a 6 week follow-up study was conducted. The study was performed in a public research hospital in Mexico City in the outpatient service of homeopathy. One hundred thirty-three peri- and postmenopausal women diagnosed with major depression according to DSM-IV (moderate to severe intensity) were included. The outcomes were: change in the mean total score among groups on the 17-item Hamilton Rating Scale for Depression, Beck Depression Inventory and Greene Scale, after 6 weeks of treatment, response and remission rates, and safety. Efficacy data were analyzed in the intention-to-treat population (ANOVA with Bonferroni post-hoc test). RESULTS: After a 6-week treatment, homeopathic group was more effective than placebo by 5 points in Hamilton Scale. Response rate was 54.5% and remission rate, 15.9%. There was a significant difference among groups in response rate definition only, but not in remission rate. Fluoxetine-placebo difference was 3.2 points. No differences were observed among groups in the Beck Depression Inventory. Homeopathic group was superior to placebo in Greene Climacteric Scale (8.6 points). Fluoxetine was not different from placebo in Greene Climacteric Scale. CONCLUSION: Homeopathy and fluoxetine are effective and safe antidepressants for climacteric women. Homeopathy and fluoxetine were significantly different from placebo in response definition only. Homeopathy, but not fluoxetine, improves menopausal symptoms scored by Greene Climacteric Scale. TRIAL REGISTRATION: ClinicalTrials.gov NCT01635218. PROTOCOL PUBLICATION: https://clinicaltrials.gov/ct2/show/NCT01635218 [corrected].

Modulatory effects of a synthetic steroid (tibolone) and estradiol on spontaneous and GH-RH-induced GH secretion in postmenopausal women.

OBJECTIVE: Since hormonal replacement therapy (HRT) affects plasma GH levels, the present study aimed to verify the effect of tibolone, a synthetic steroid, on modulating spontaneous and growth hormone releasing hormone (GH-RH) induced GH secretion. METHODS: Postmenopausal women (n = 30) were enrolled and randomly subdivided in three groups (n = 10 each group): (1) treated with transdermal estradiol (50 micrograms) (Dermestrill, Rottapharm, Monza, Italy) biweekly; (2) treated with transdermal estradiol (100 micrograms) (Dermestrill, Rottapharm, Monza, Italy) biweekly; (3) treated with tibolone 2.5 mg/day (Livial, Organon Italia, Rome, Italy). Patients underwent a GH-RH test (1 microgram/kg) and 15 of them underwent to a pulsatility study before and 5 weeks after treatment. RESULTS: Mean (+ S.E.M.) GH plasma levels increased in all patients after any type of HRT. GH response to GH-RH stimulation (expressed as maximal response to GH-RH or as delta value) was similar in the three groups while significant changes occurred in spontaneous pulsatile GH release. Tibolone and both dosages of transdermal estradiol significantly reduced GH pulse frequency and increased pulse amplitude. CONCLUSIONS: The reduced plasma GH levels observed during postmenopause are probably related to a reduced endogenous GH-RH and not to a reduced pituitary ability to respond to GH-RH. In addition tibolone, as well as transdermal estradiol, are effective in restoring the spontaneous GH episodic release.

Effects of tibolone on the breast of postmenopausal women.

For decades, hormone therapy (HT) has been the mainstay for managing menopausal symptoms. However, the prolonged use of either single estrogen therapy (ET) or a combination therapy of estrogen and progestogen (EPT) might be associated with a slightly increased risk of breast cancer. Alternative therapies that are effective in the prevention and/or treatment of menopause, having associated morbidities but no unwanted effects, are of primary interest in clinical practice. Tibolone (Livial; NV Organon, Oss, The Netherlands) is structurally related to 19-nortestosterone derivatives and is a new postmenopausal regimen with a unique pharmacological profile, licensed for the relief of climacteric symptoms and the prevention of osteoporosis in postmenopausal women. Tibolone exhibits weak estrogenic, progestogenic, and androgenic activities, which in theory might influence the breast. The effect of tibolone on breast tissue, however, is obscure. The purpose of this study was to assess the effects of tibolone on breast safety, and the collected data include preclinical models, clinical observation, and epidemiologic study. Although in vitro studies showed conflicting results (with the majority being favorable effects) regarding the effects of tibolone on breast cells, in vivo studies showed favorable effects of tibolone on the breast in animal models. Similarly, an epidemiologic study indicated an increased risk of breast cancer when tibolone was used to manage climacteric symptoms of postmenopausal women, but accumulated data obtained from radiologic studies (mammography) showed a possible protective effect of tibolone on the breast. Taken together, we conclude that tibolone, if not superior to conventional HT, may be more acceptable to clinicians as a therapeutic drug option for use with symptomatic menopausal women. Only time will tell whether tibolone will be the preferred option.