Maranho Maria Clara de Morais Faleiros, Guapo Vinicius Guandalini, de Rezende Marcos Gonçalves, Vieira Carolina Sales, Brandão Marcus Lira, Graeff Frederico Guilherme, Lovick Thelma, Del-Ben Cristina Marta
Department of Neuroscience and Behavior, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil; Department of Internal Medicine, Barão de Mauá University Center, Ribeirão Preto, Brazil.
Department of Neuroscience and Behavior, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
Psychoneuroendocrinology. 2023 Nov;157:106360. doi: 10.1016/j.psyneuen.2023.106360. Epub 2023 Aug 9.
The neuroactive metabolite of progesterone, allopregnanolone (ALLO), has been implicated in premenstrual syndrome (PMS) physiopathology and preclinical studies suggested that low doses of fluoxetine increase the ALLO brain concentration.
To assess which low dose of fluoxetine (2 mg/d, 5 mg/d or 10 mg/d), administered exclusively during the luteal phase of menstrual cycle, has a potential effect for preventing or mitigating emotional PMS symptoms.
In this randomized, double-blind, placebo-controlled pilot study, we followed 40 women (mean age = 29.7 +/- 7.4 years) with emotional PMS, during two menstrual cycles: cycle 1, without pharmacological intervention; and cycle 2, with pharmacological intervention. Participants took capsules, on average, seven days preceding the likely date of menses. We assessed the severity of PMS symptoms in both cycles using the Daily Record of Severity of Problems scale (DRSP).
There was an increase in the DRSP scores during the late luteal phase of cycle 1, confirming the diagnosis of emotional PMS. Low doses of fluoxetine (5 mg/d: 33.5%; 10 mg/d: 48.4%) reduced DRSP total score in the day before menses (day-1) at cycle 2 compared with day-1 at cycle 1. Fluoxetine 10 mg/d had the most consistent decline in emotional PMS symptoms; 70% of the participants reported a reduction greater than 40% in the DRSP score.
Low doses of fluoxetine, which may have no or few effect on the serotonergic system, but may interfere in the progesterone metabolization, seem to have some potential to mitigate emotional PMS symptoms. While the 10 mg/d of fluoxetine had the best performance on reducing emotional PMS symptoms, the 5 mg/d dose also seems to have some effect on emotional PMS symptoms. Further larger studies will help establish the lowest effective dose of flouxetine for PMS treatment.
孕酮的神经活性代谢产物别孕烷醇酮（ALLO）与经前综合征（PMS）的病理生理有关，临床前研究表明低剂量氟西汀可提高脑内ALLO浓度。
评估在月经周期黄体期单独服用哪种低剂量氟西汀（2mg/d、5mg/d或10mg/d）对预防或减轻PMS情绪症状有潜在作用。
在这项随机、双盲、安慰剂对照的试点研究中，我们对40名患有PMS情绪症状的女性（平均年龄=29.7±7.4岁）进行了两个月经周期的随访：第1周期，无药物干预；第2周期，进行药物干预。参与者平均在预计月经日期前7天服用胶囊。我们使用问题严重程度每日记录量表（DRSP）评估两个周期中PMS症状的严重程度。
第1周期黄体晚期DRSP评分增加，证实了PMS情绪症状的诊断。与第1周期的月经前1天（第-1天）相比，低剂量氟西汀（5mg/d：33.5%；10mg/d：48.4%）在第2周期月经前1天降低了DRSP总分。10mg/d氟西汀对PMS情绪症状的缓解最为持续；70%的参与者报告DRSP评分降低超过40%。
低剂量氟西汀可能对5-羟色胺能系统无影响或影响较小，但可能干扰孕酮代谢，似乎有减轻PMS情绪症状的潜力。虽然10mg/d氟西汀在减轻PMS情绪症状方面表现最佳，但5mg/d剂量似乎也对PMS情绪症状有一定作用。进一步的大型研究将有助于确定治疗PMS的氟西汀最低有效剂量。
