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| Serotonin Study Raises Questions About M2F Hormone Cycling |
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| SciMed - Neuroscience | |||
| TS-Si News Service | |||
| Friday, 15 February 2008 19:00 | |||
Stockholm, Sweden. A neurotransmitter is a chemical that permits nerve signals to bridge the gap, or synapse, between nerve cells. Basically, it is a chemical used as a messenger from one nerve cell to another. Serotonin is believed to play an important role as a neurotransmitter in the central nervous system and is critical to the development and treatment of depression and chronic anxiety. These conditions have been documented as much more common in women than in men.  A research group at the Swedish medical university, Karolinska Institutet, scanned the brains of men and women using Positron Emission Tomography (PET). The scans showed there are different serotonin systems for the sexes (yellow), with differing numbers of binding sites, or receptors (red), for serotonin in certain parts of the brain.
The researchers also defined the sensitivity of the female serotonin system to fluctuations in female hormone levels.
PET evaluation of central serotonergic neurotransmission in women. Jovanovic, Hristina (2008). (Doctoral dissertation, Karolinska Institutet, 2008). ISBN: 978-91-7357-510-2.
This is a subject of direct interest for M2F patients with a history of Harry Benjamin Syndrome (HBS). Strictly speaking, such patients are neither pre-menopausal nor post-menopausal. Some HBS patients advocate the practice of hormone "cycling" to match the fluctuations typical of natal females. Proponents justify the approach as more "natural" since it is thought to emulate the menstrual cycle.
 The research findings, presented in a doctoral thesis by Hristina Jovanovic, show that women have a greater number of the most common serotonin receptors than men. They also show that women have lower levels of the protein that transports serotonin back into the nerve cells that secrete it. This is the protein blocked by the most common antidepressants (SSRIs).  “We don’t know exactly what this means, but the results can help us understand why the occurrence of depression differs between the sexes and why men and women sometimes respond differently to treatment with antidepressant drugs,” says associate professor Anna-Lena Nordström, who led the study. The serotonin system in healthy women differs from that in women with serious premenstrual mental symptoms.
So far, the research results suggest that the serotonin system in such women does not respond as flexibly to the hormone swings of the menstrual cycle as that in symptom-free women.
The research results carry an implied warning to HBS patients, whether pre- or post-op, who cope with depression and/or chronic anxiety. They may be bettter served by the consistent use of hormone dosages to minimize their symptoms. A separate and focused study would be necessary to determine the applicability of the current research results to hormone treatments for M2F patients.
In any case, “These findings indicate that when developing antidepressants and anti-anxiety drugs, scientists should evaluate their effect on men and women separately, as well as their effects before and after menopause,” says Ms. Nordström.
Positron Emission Tomography (PET), also referred to as PET imaging or a PET scan, is a specific type of nuclear medicine imaging, a subspecialty within the field of radiology. PET scans use very small amounts of radioactive material to diagnose or treat diagnose medical conditions, as well as identify structures within the body. Such imaging procedures are noninvasive and usually painless.
Depending on the particular type of nuclear medicine exam, a radiotracer is injected into a vein, swallowed by mouth or inhaled as a gas. The material eventually collects in the area under examination and emits energy as gamma rays. These emissions can be detected by a device called a gamma camera, a (positron emission tomography) PET scanner and/or probe.
One or more of these devices work together with a computer to measure the amount of radiotracer absorbed by your body. Once processed, the measurements are used to produce special pictures offering details on both the structure and function of organs and other internal body parts.
PET evaluation of central serotonergic neurotransmission in women. Jovanovic, Hristina (2008). (Doctoral dissertation, Karolinska Institutet, 2008). ISBN: 978-91-7357-510-2.
Abstract
The serotonin (5-HT) system is of central interest in the patophysiology and treatment of several psychiatric disorders including depression, anxiety and suicide. In women, functioning of the 5-HT system is of particular importance since they have been found to suffer more often from 5-HT-associated disorders compared to men. The aim of the present thesis was to further explore the central serotonergic system in women by examining 5- HT1A receptors and 5-HTT binding in two psychiatric disorders, borderline personality disorder (BPD) and premenstrual dysphoric disorder (PMDD), during different phases of the menstrual cycle and in relation to gender.
In the first study positron emission tomography (PET) and [11C]WAY100635 were used to examine 5-HT1A receptors in control group of women and in women with PMDD. Two PET examinations were performed in each subject, one before (follicular phase) and one after ovulation (luteal phase). The 5-HT1A binding potential (BP) was measured in six regions of interest and calculated according to the simplified reference tissue model (SRTM). For the region of dorsal raphe nuclei, there was a significant difference between the groups in the change of 5-HT1A receptor binding. The study provides principally new support in vivo, for a serotonergic dysregulation in women with PMDD.
In the second study, PET and selective radioligands [11C]WAY100635 and [11C]MADAM were used to study differences in 5-HT1A receptors and 5-HTT BPs between healthy women and men. The BPs were estimated both on the level of anatomical regions and voxel wise, derived by the SRTM and wavelet/Logan plot parametric image techniques respectively. The volume of interest (VOI)-based analysis revealed higher mean 5-HT1A BP and lower mean 5-HTT BP values in women compared to men. The parametric analysis of [11C]WAY100635 and [11C]MADAM images showed similar results to those obtained with VOI analysis. In women, a positive correlation between 5-HT1A receptor and 5-HTT BPs for the region of hippocampus was found. Sex differences in 5-HT1A receptor and 5-HTT binding may reflect biological distinctions in the 5-HT system contributing to sex differences in the prevalence of psychiatric disorders such as depression and anxiety. The result may help understanding sex differences in drug treatment responses to drugs affecting the 5-HT system.
In the third study, healthy women were investigated in the follicular and luteal phase of the menstrual cycle with radioligands [11C]WAY100635 and [11C]MADAM to study 5-HT1A and 5-HTT BPs. The BPs values were quantified using the SRTM. The phases of the menstrual cycle were characterized by transvaginal ultrasound (TVS) and plasma levels of hormones estradiol (E2), progesterone (P4), follicle stimulating hormone (FSH) and luteinising hormone (LH). The 5-HT1A receptor and 5-HTT BPs did not significantly differ between follicular and luteal phases in any of the investigated regions. There were no significant correlations between hormones E2 or P4 and 5-HT1A receptors BP or 5-HTT BP in any of the regions, neither did the change in plasma E2 or P4 correlate with the change in 5-HT1A BP or 5-HTT BP values in brain regions. The results provide principally new in vivo evidence on human female biology, suggesting no difference in 5-HT1A receptors and 5-HTT binding between the phases of the menstrual cycle in healthy women that can be revealed with the present methodology.
In the fourth study, 5-HT1A receptor BP in female patients with BPD and controls were examined. Out of two hundred female patients with BPD, seven met inclusion criteria (i.e. drug naïve including, no previous or present alcohol or drug abuse/dependency). Eight age and sex matched controls were recruited. PET and selective radioligand [11C]WAY100635 were used to study brain 5-HT1A receptor BP in dorsolateral prefrontal cortex, anterior cingulate, orbitofrontal cortex, amygdala, hippocampus, insula, temporal cortex and dorsal raphe nuclei. BP was estimated using the SRTM. Compared to controls, women with BPD had a significantly lower 5-HT1A receptor BP in the brain regions examined. The results suggest a lower 5-HT1A receptor BP in drug naïve patients with BPD. The finding corroborates previous studies suggesting the impairment of the 5-HT system in patients with BPD.
In conclusion, the present thesis provides new evidence for the implication of the serotonin system in psychiatric disorders in women, effects of gonadal hormones and sex differences in serotonergic neurotransmission.
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