Menopause Live - IMS Updates

Date of release: 22 February, 2010

Read this, not that

Busy clinicians may be well-tempted to scan their monthly stack of journals and narrow down the reading list to a manageable few articles that may have some immediate gratification and perhaps find a study concerning a problem they had encountered just this week. Journal articles with esoteric words in the title can be a big turn-off, even for many earnest professionals. Take, for instance, the term ‘brain-derived neurotrophic factor’. When you are four patients behind, there are three calls on hold, and you are just a skosh stressed, reading about neurotrophic factors may seem a tad unnecessary. That would be a mistake. Every month Menopause and Climacteric journals successfully sift through mountains of rock-hard data to bring to light a selected few important nuggets. As in the immensely popular diet books by David Zinczenko, Eat This Not That, busy clinicians can trust those two journals to deliver information worthy of your time and trouble to read.  


Reproductive hormones have historically been known to influence brain function via steroid-specific neural receptors. Recent years have brought to light evidence that estrogen has direct and indirect effects in altering several brain neurotransmitters, including, importantly, serotonin and neurotrophins. During postmenopause, either natural or induced, a measurable decline in neurotrophins, such as brain-derived neurotrophic factor (BDNF), can be reversed with exogenous estrogen. Administration of serotonin specific re-uptake inhibitors (SSRIs), such as paroxetine, has a similar effect. BDNF has been an item of interest for several years because of its apparent role in neural growth, plasticity and function. BDNF is felt to have a pivotal role in cognition and memory. Serum BDNF levels have been shown to decline with age and time since menopause. A recent study advances the clinical implications of this important linkage [1]. 


From a pool of 119 symptomatic postmenopausal women, 89 were self-selected to treatment with low-dose paroxetine 10 mg/day, while the second group chose menopausal hormone therapy consisting of estradiol valerate 2 mg/day plus levonorgestrel 0.0075 mg/day. Pretreatment labs and the Greene Climacteric Scale scores (GCS) were obtained and compared at 3 and 6 months. Before treatment, both groups had similar scores and test results. After 3 months of paroxetine, BDNF levels significantly increased while menopausal symptoms decreased (vasomotor, sexual desire, mood, and somatic complaints). After 6 months on paroxetine, there was noted a further significant increase in BDNF levels and additional improvement (lower scores) in the scales derived from the GCS. Because the decline in BDNF is so steep and correlated with age, the beneficial improvement seen with paroxetine only lessened the slope of the decline but did not flatten it out or increase it. In contrast, women who took estrogen for 6 months had BDNF ‘restored’ to levels comparable to those in young fertile women.


SSRIs have been increasingly used for vasomotor complaints in peri- and postmenopausal women, and this study confirms this clinically important role while, at the same time, expanding our understanding of the complicated neural substrates that underlie its action. Paroxetine favorably affects other seemingly diverse menopausal complaints and is not limited to improvement of mood. The authors synthesize a large volume of diverse information into good cohesive science with great clinical implications. As all excellent studies do, this one particularly begs for more questions to be answered. How different might a randomized, placebo-controlled trial look? (Oh, if only the expense were not a factor!) Would there be any difference if the menopausal hormone therapy consisted of transdermal 17β-estradiol with oral progesterone instead of progestin? Would clinically relevant cognitive tests further the distinction between the two treatment arms? And, why do the majority of perimenopausal and early postmenopausal women still feel that the risks of menopausal hormone therapy outweigh the benefits?


David C. Miller and Lovera Wolf Miller
Health 4 Her, Michigan City, Indiana, USA


  1. Cubeddu A, Giannini A, Bucci F, et al. Paroxetine increases brain-derived neurotrophic factor in postmenopausal women. Menopause 2009 November 20; Epub ahead of print.