Estrogen receptor 1 (ESR1) and ESR2 gene polymorphisms have been associated with endocrine-mediated physiological mechanisms, and inconsistently with breast cancer risk and outcomes, bone mineral density changes, and hot flushes/night sweats.
Novel ligands balance estrogen receptor β and α agonism for safe and effective suppression of the vasomotor response in the ovariectomized female rat model of menopause.
Women who had the ESR2-02 AA genotype were significantly less likely to experience tamoxifen-induced hot flashes than women who carried at least one ESR-02 G allele (hazard ratio, 0.26; 95% CI, 0.10 to 0.63; P = .001).
Associations of CYP2D6 metabolism phenotypes with breast cancer-free interval (referred to as recurrence) and treatment-induced hot flushes according to randomized endocrine treatment and previous chemotherapy were assessed.
CYP2D6 activity can also be reduced by concomitant use of drugs that inhibit the enzyme, including antidepressants used for psychiatric conditions or to relieve hot flashes, and these should be avoided in tamoxifen users whenever possible.
Strong and intermediate inhibitors of CYP2D6, which may be used to treat hot flashes or psychiatric conditions in breast cancer patients, can also negatively impact enzyme function.
These interrelations are particularly critical for patients with non-functional (poor metaboliser) and severely impaired (intermediate metaboliser) CYP2D6 variants, and, moreover, for patients in need of co-medication such as serotonin re-uptake inhibitors to control adverse effects such as hot flashes and other menopausal symptoms.
Moreover, strong CYP2D6 inhibitors such as the selective serotonin reuptake inhibitors paroxetine and fluoxetine, which are used to treat hot flashes, should be avoided because they severely impair formation of the active metabolites.
Women with the CYP2D6 *4/*4 genotype had worse relapse-free time (RF-time; P = .023) and disease-free survival (DFS; P = .012), but not overall survival (P = .169) and did not experience moderate to severe hot flashes relative to women heterozygous or homozygous for the wild-type allele.
We examined the effects of concomitant use of selective serotonin reuptake inhibitor antidepressants, which are CYP2D6 enzyme inhibitors commonly prescribed to treat hot flashes in women who take tamoxifen, and genotypes for genes that encode tamoxifen-metabolizing enzymes on plasma concentrations of tamoxifen and its metabolites.
In this retrospective case-control study, we were unable to identify a detrimental effect of depomedroxyprogesterone acetate therapy for hot flashes in survivors of estrogen receptor-expressing breast cancer.
In recent years, NKB, predominantly acting via the neurokinin 3 receptor (NK3R), has emerged as an important player in the development of menopausal hot flushes.
Within this review, we will explore the growing body of evidence supporting antagonism of NK3R as a potentially promising treatment for menopausal hot flushes.
We conclude that transient activation of Kiss1<sup>ARH</sup> neurons following sex-hormone withdrawal contributes to the occurrence of hot flushes via NkB release in the rostral preoptic area.
Randomized, double-blind, placebo-controlled, single-center, crossover trial of an oral NK3R antagonist (MLE4901) for vasomotor symptoms in women aged 40 to 62 years, experiencing ≥7 HF/24 hours some of which were reported as bothersome or severe (Clinicaltrials.gov NCT02668185).
Over the last 20 years, numerous studies in animal and human models have implicated neurokinin B, a hypothalamic neuropeptide, together with its receptor (NK3R) in the etiology of menopausal hot flushes.
Over the last 20 years, numerous studies in animal and human models have implicated neurokinin B, a hypothalamic neuropeptide, together with its receptor (NK3R) in the etiology of menopausal hot flushes.