Since the new year I have seen two people, one young and with life-long unrecognized hyperthyroid symptoms and signs, and the other a late middle aged person having just undergone bariatric stomach surgery in the setting of long-term hypothyroid-related obesity, who both have had a remarkable normalization of their health with minimal medication interventions. The first is a 22-year male with nearly life-long problems with severe anxiety, insomnia, sudden jags of 40-pound weight loss and then regain, tremor, fatigue, inappropriate hotness all the time, sweaty, oily skin, a racing heart that jumps to 140 beats per minute and occasionally 200... Continue reading

On March 29, 2011 I wrote about a log-term neuroprotective role of estradiol on womens' brains and framed this data in the evolving field of the risks and benefits to women of hormone replacement therapy (HRT) around the time of menopause. In fact, the Alzheimer's Disease (AD) field has evolved to thinking that there is a 7-year window following the onset of menopause during which time exposure to estradiol or HRT can confer log-term protection from AD, whereas once the window closes such protection may be lessened or lost. Now, three recent studies provide important information to help women and... Continue reading

In April 6, 2010 I blogged here on A Neuroendocrine Approach to Finasteride Side Effects in Men. Now I am reporting on how we've done over the past 3 years caring for around 300 men sufferring from Post Finasteride Syndrome (PFS). First, the group of 300 + men presenting with sexual dysfunction while on finasteride, or recently or not-so-recently off it, did all show a similarly abnormal hormonal profile called hypogonadotropic hypogonadism or HH, which means low testosterone along with low LH and FSH, the pituitary hormones that stimulate the gonads. However, the group was otherwise not monolithic. In fact,... Continue reading

In recent months I have seen a number of patients who presented with "thyroid problems" that did not fit neatly into any box. As a rule, they came armed with lab test results showing that anytime they took L-thyroxine (T4), not only did they continue feeling untreated/hypothyroid, but also that their serum levels of reverse T3 (rT3) would markedly increase. They wondered if they were "thyroid resistant" and in one sense of the term, they were. Thyroxine (T4) has 4 iodine binding sites filled by 4 iodine molecules. In the normal course of thyroid hormone functioning, the active hormone, tri-iodothrionine... Continue reading

Researchers from the University of Pennsylvania Medical Center (Dokras, Anuja et al.) have published a new systematic review and meta-analysis in a November 29 online report in Fertility and Sterility investigating the prevalence of anxiety disorders in women with polycystic ovary syndrome (PCOS). They found 5 times as many women with PCOS having generalized anxiety symptoms compared with controls (prevalence - 20% vs. 4%) and a nearly sevenfold increase in the risk of generalized anxiety symptoms in women with PCOS (pooled odds ratio, 6.88). They also found studies showing a higher prevalence of social phobia in women with PCOS and... Continue reading

I saw a patient who was referred because of low sodium levels (hyponatremia). He had experienced a very mild blunt head trauma and his doctors thought this had led to the hyponatremia due to the hormonal disorder called the syndrome of inappropriate antidiuretic hormone (SIADH). Antidiuretic hormone (ADH) is normally secreted from the pituitary gland when sodium levels in the blood get too high and water needs to be reabsorbed from the kidney's filtered blood to dilute the blood back to normal. If you make too much AHD you retain too much water in the blood and the concentration of... Continue reading

There is growing scientific support for a neuroprotective role of estrogen in women as they age, even as the question still exists as to whether there are risks to brain function that could outweigh the benefits of postmenopausal hormal replacement. In a new study (Differences in regional brain metabolism associated with specific formulations of hormone therapy in postmenopausal women at risk for AD, Psychoneuroendocrinology (2011) 36, 502-513), Daniel H.S. Silverman et al. publish the results of a prospective, randomized longitudinal clinical trial in which postmenopausal women age 50-65 on different formulations of hormone replacement therapy and at increased risk for... Continue reading

Two recent articles offer us bookends around the topic of overweightness, prediabetes and diabetes, and brain dysfunction. At one end is a study by Laura Baker, PhD, et al. (Arch Neurol/vol 68 (No.1), Jan 2011 pp 51-7.), which showed that insulin resistance in cognitively normal adults around 70 years old with prediabetes or diabetes was associated with a pattern of decreased brain function on positron emission tomagraphy (PET) scans that mimicked the same pattern seen on PET scans of patients with early Alzheimer's disease (AD). Moreover, when compared to healthy adults matched for age, education, body mass index and fasting... Continue reading

The persitence of male sexual side effects (hypogonadism) after discontinuation of finasteride is a serious problem for a significant subset of men who use the drug. I had previously written about whether the propensity of finasteride to cause lasting hypogonadism could be due to the development of partial androgen resistance and whether this relates to the number of CAG repeats in exon 1 of their androgen receptor genes. Recently, a patient of mine brought to my attention a research paper from Csoka, et al.(J Sex Med 2008;5:227-233) titled "Persistent Sexual Dysfunction after Discontinuation of Selective Serotonin Reuptake Inhibitors". They added... Continue reading

In response to a recent question posed to me from a woman concerning what to expect in terms of the frequency of her seizures as she goes through a pregnancy and breastfeeds her baby, I though it would be useful to expand on this topic in a blog post - a sort of "what to expect when you are expecting" from a catamenial epilepsy/neuroendocrinology perspective. Recall that estrogen provokes epileptic seizures and progesterone inhibits them. When a woman becomes pregnant the cyclic production of estrogen and progesterone that brought the catamenial onset of seizures comes to an end and the... Continue reading

The wealth of recent public interest in, and scientific investigation of, testosterone as a neuroprotective hormone that can increase brain cell defenses against Alzheimer's disease(AD)-related insults in men and the rising demand to test optimal ways of using androgens in men to delay, prevent, and or treat AD has reintroduced the idea of giving elderly men testosterone therapy. Two recent articles from June 2010 in the New England Journal of Medicine have looked directly at the issue of testosterone and its safety and proper use in older men and attempt to further our larger understanding of how to incorporate hormone... Continue reading

Several young men seen for hypogonadism (low libido, erectile dysfunction, low energy, etc) after using finasteride have been found to have low-normal levels of bio-available testosterone and LH. This leads to the question of whether partial androgen resistance is at play. It has been shown that androgen insensitivity can occur even without mutations in the genes coding for the androgen receptor1. How then to connect finasteride use to the development of partial androgen resistance, especially outlasting the use of the drug? In recent years many scientists have looked at the androgen receptor gene with an eye towards a variable length... Continue reading

Another interesting Mens' issue in Neuroendocrinology has recently been in the scientific news concerning testosterone and Alzheimer disease (AD). Testosterone's brain protective properties have been suggested based on observations linking low blood levels of testosterone with increased risk for AD in older men. There is ample evidence from population-based and animal-based studies that testosterone protects brain cells, even from beta-amyloid, the protein thought to be a major player in causing AD. However, many scientists thought testosterone's benefits came indirectly from its conversion to estrogen in brain cells. As I have blogged about before, the enzyme aromatase does this conversion. Now... Continue reading

As I involve myself in the biology underlying the finasteride and post-finasteride-associated hypogonadal syndrome and parallel "brain fog" syndrome many men experience, I have focused on the metabolism of dihydrotestosterone (DHT), the hormone that finasteride inhibits by virtue of its blockage of the 5-alpha reductase enzyme that normally converts testosterone to DHT (along with several other reactions it normally does that form potent neuroactive anti-anxiety and seizure preventing hormones in the brain). Moreover, I have written here about the role of estrogen in the brains of women (e.g. cognition, neuroprotection) and the fact that we men need estrogen in our... Continue reading

This past summer in Vienna at the International Conference on Alzheimer's Disease (ICAD2009) I saw interesting research concerning certain personality types and their effects on healthy or unhealthy brain aging. By a widely accepted model there are 5 general personality traits represented by the word 'OCEAN': Openness, Conscientiousness, Extroversion, Agreeableness and Neuroticism. Data presented links scoring high in the trait of Neuroticism (the tendency to experience negative or unstable moods and increased stress levels), with increasing ones odds of cognitive loss/dementia later in life, and that scoring low in Conscientiousness (the tendency to be organized, thorough and reliable) is also... Continue reading

One of the important issues women consider when deciding whether or not to use postmenopausal hormone replacement and which preparations to use and for how long to use them, is to garner protection from Alzheimer's disease(AD), and/or to maintain or attain healthy brain aging and thus avoid cognitive decline as they age. A recent study published in the journal Neurology (2010;volume 74: pages 807-815) sheds important light on this subject. But before I discuss the study I want to discuss one important biological fact that is thought to explain at least partly why women get AD more commonly than men,... Continue reading

I had mentioned in a previous post that one way to become a neuroendocrine patient is to possess an anomalous brain in the setting of normal hormones (the other ways were - normal brain, anomalous hormones and anomalous brain, anomalous hormones). Here is a research study that demonstrates this idea in the context of premenstrual syndrome (PMS) from N Engl J Med. 1998 Jan 22;338(4):209-16. PJ Schmidt et al. from the National Institute of Mental Health set out to induce a reversible chemical menopause in 40 women split into 2 groups - 20 with PMS and 20 without PMS(normal). They... Continue reading

This week I am summarizing a recent interesting article concerning the relationship between menopause and cognition, as influenced by estrogen exposure. I have long wondered whether the subset of women who experience cognitive changes/decline associated with the menopausal transition do so because of estrogen decline directly or because of an underlying risk profile relating decreased brain levels of estrogen to preclinical Alzheimer's disease. Accelerated postmenopausal cognitive decline is restricted to women with normal BMI: Longitudinal evidence from the Betula project Psychoneuroendocrinology, May 2010. Vol. 35, Issue 4, Pages 516-524. Petra P. Thilers, Stuart W.S. MacDonald, Lars-Göran Nilsson, Agneta Herlitz The... Continue reading

An important piece of the neuroendocrine puzzle that brings together our hormones and our behavior, leading to conditions such as premenstrual syndrome (PMS), catamenial epilepsy and stress related menstrual disorders is the area of our brains called the temporal lobes. We each have a right and left temporal lobe on each side of our brain. They point forwards on each side like very large thumbs, with the tips pointing forwards towards the backs of our eyes. The lateral side of the temporal lobe could be seen directly if one were looking at a brain from the side. The inner or... Continue reading

I have recently seen an increasing number of men who have developed significant degrees of clinical hypogonadism - low sex drive, erectile dysfunction, reduced sexual sensations and listlessness, fatigue and/or "brain fog" - while either taking finasteride or after stopping the medication, even long after stopping it. Finasteride is a medication approved by the FDA to treat benign prostate enlargement and testosterone-related hair loss. It does so by blocking the function of an enzyme called 5-alpha reductase. This enzyme normally converts testosterone to dihydrotestosterone (DHT), which is a more potent hormone that acts at the prostate and the hair follicles.... Continue reading

Not all women experience changes in their neurological or emotional well being because of their hormones, only a subset do. Studies investigating why have found, for example, that women who rate themselves as having significant premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD) are also found to have a higher occurrence of mild changes on EEG-brain wave tests, subtle right/left differences on neurological examination, family members with depression, a past history of concussion, migraine headaches or even left-handedness, compared to women without PMS or PMDD. These anomalous brain conditions seem to bring anomalous brain responses to hormones. A dramatic example... Continue reading

A classic, not uncommon neuroendocrine syndrome is the relationship between chronic stress, the adrenal steroid hormone cortisol and both the size of the hippocampus and its memory functioning. Some studies have looked at this, for example, by taking large groups of people and asking them to record how much stress they have experienced over time. These stressors could involve financial, occupational, marital and health related matters. Subject also have their cortisol blood levels measured, their memory tested and the size of their hippocampi measured by brain MRI. The hippocampus is part of the temporal lobes of the brain and is... Continue reading

I previously detailed 3 well-described patterns of catamenial symptoms that women report: Type 1 - premenstrual, Type 2 - peri-ovulatory (mid-cycle), and Type 3 - luteal (throughout the 2 weeks from midcycle to menses). Here I want to describe how and why the two reproductive hormones, estrogen (E2) and progesterone (P), have a yin / yang effect on the brain, so that these 3 patterns make sense. Firstly, these hormones cause changes in our emotions and brain functioning by binding to specific docking sites (receptors) on specific brain cells in specific areas of the brain. Estrogen is the yin. When... Continue reading

When a woman comes for a neuroendocrine consultation to get help with hard-to-control seizures or troubling emotional changes, my ability to help her increases greatly when she has observed a ‘catamenial’ pattern to the occurrence of her symptoms (meaning they occur at a specific time during her menstrual cycle on a repeating basis). In fact, I have been faced with very unusual symptoms in some of my female patients, like shaking spells and psychotic symptoms that, because of a catamenial pattern, responded well to hormonal-based therapies. In my last blog entry I introduced 3 patterns of catamenial occurrence of symptoms:... Continue reading