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Endocrine Care: Susan Thys-Jacobs, Don McMahon, and John P. Bilezikian Differences in Free Estradiol and Sex Hormone-Binding Globulin in Women with and without Premenstrual Dysphoric Disorder J Clin Endocrinol Metab 2008; 93: 96-102 [Abstract] [Full text] [PDF]

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Response to PMDD and Its Elusive Causes

Susan Thys-Jacobs, Don McMahon, John P. Bilezikian MD   (11 February 2008)

PMDD and It's Elusive Causes

Christopher B Cutter   (4 February 2008)

Response to PMDD and Its Elusive Causes 11 February 2008
Susan Thys-Jacobs, MD St. Lukes-Roosevelt Hospital, College of Physicians & Surgeons, Columbia University, Don McMahon, John P. Bilezikian MD Send letter to journal: Re: Response to PMDD and Its Elusive Causes sthysja{at}chpnet.org Susan Thys-Jacobs, et al.	Premenstrual dysphoric disorder (PMDD) has been indeed an elusive and poorly understood disorder. Over the years, different hypotheses involving the ovarian steroid hormones, specifically estradiol and progesterone, have been proposed to explain the luteal phase occurrence of severe PMS symptoms. Most investigations to date, had not substantiated consistent differences in the concentrations of either estradiol or progesterone between symptomatic or asymptomatic women, although the controversy on estradiol persisted (1-4). Cutter notes the near comprehensive evaluation of our investigation with the significant differences found in free E2, % free E2 and SHBG between women with and without PMDD. He argues for the potential importance of testosterone, another sex steroid hormone, in the pathogenesis of PMDD. Our investigation was designed to collect data on estrogenic steroids, hormones, electrolytes and indices of calcium homeostasis for which existing data in the literature provided evidence that might relate these measures to PMDD etiology. Cutter does not provide citations to indicate that androgenic steroids might also be a potential target. However, we concur that differences in the levels of testosterone or even aromatase activity could have a role in premenstrual irritability or dysphoria. Only further investigation will be able to elucidate this point. References 1. Rubinow D, Hoban C, Grover GN, Galloway DS, Roy-Byrne P, Andersen R, Merriam G. 1988 Changes in plasma hormones across the menstrual cycle in patients with menstrually related mood disorder and in control subjects. Am J Obstet Gynecol 158:5-11 2. Hsiao CC, Liu CY, Hsiao MC. 2004 No correlation of depression and anxiety to plasma estrogen and progesterone levels in patients with premenstrual dysphoric disorder. Psychiat Clin Neurosci 58: 593-599 3. Seippel L, Backstrom T. 1998 Luteal phase estradiol relates to symptom severity in patients with premenstrual syndrome. J Clin Endocrinol Metabol 83:1988-1992 4. Wang M, Seippel L, Purdy R, Backstrom T. 1996 Relationship between symptom severity and steroid variation in women with premenstrual syndrome. J Clin Endocrinol Metabol 81:1076-1082
PMDD and It's Elusive Causes 4 February 2008
Christopher B Cutter, Physician Savoy Medical Center Send letter to journal: Re: PMDD and It's Elusive Causes ccutter{at}centurytel.net Christopher B Cutter	Thys-Jacobs et al. (1) presented an elegant and near-comprehensive evaluation of the hormonal factors that may cause premenstrual dysphoric disorder (PMDD) in reproductive age women. In their paper they described higher free E2 levels in the asymptomatic females, suggesting a causal relationship between low E2 and PMDD. Unfortunately, these investigators did not report the levels of another important ovarian steroid, testosterone, and its possible relationship to this complex disorder. Using the data that they presented, with SHBG levels of 61.4 nmol/liter vs. 52.4 nm/liter, and albumin levels of 4.4 and 4.3 g/dl, respectively, I calculated what the free testosterone levels might be if both symptomatic and control groups had equal luteal T levels of 40 ng/dl (2). This would yield a free T of 0.47 ng/dl vs. 0.53 ng/dl in symptomatic vs. control patients (a 12% increase over symptomatic women). However, if the T levels were actually measured, it is likely that the T values could be markedly different between groups, since serum levels of T are well known to be a cause of lower SHBG in humans (3). This would result in even lower levels of free T in symptomatic women. For example, if the PMDD group had a mean T level of 30 ng/dl, vs 40 ng/dl in the asymptomatic women, then the calculated free T levels would be 0.355 ng/dl vs 0.534 ng/dl, respectively. This would yield a 50% increase in the asymptomatic women – possibly yielding an even lower P value than reported for the luteal free E2 levels. Ever since the pioneering work of Dalton in the 1950s (4), physicians treating women have sought to find effective, safe and simple methods of treating those who suffer with debilitating PMDD. The treatments have run the gamut of progesterone, testosterone, estradiol, SSRIs, diuretics and herbal remedies to name just a few. Most of these interventions have not withstood the scrutiny of double-blinded trials. Hopefully, continued work as done by these dedicated researchers, will eventually yield an answer that will consistently benefit our patients. References 1. Thys-Jacobs S, McMahon D, Bilezikian JP 2008 Differences in Free Estradiol and Sex Hormone Binding Globulin in Women with and without Premenstrual Dysphoric Disorder. J Clin Endocrinol Metab 93:96-102 2. Fiers T, Kaufman JM http://www.issam.ch/freetesto.htm (Free and Bioavailable Testosterone Calculator) 3. Nieshlag E, Behre H 2004 Testosterone Action Deficiency in The Pathobiology of Androgens in Women, Burger N, Casson P, eds. Cambridge University Press 543-569 4. Dalton K 1978 in Once A Month (originally published in Great Britain by Fontana Books)