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The Agony of Ecstasy

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Panic Attack, screenshot of James in Vertigo by Alfred Hitchcock, 1958 by Wikimedia Commons

Link to original article: Click Here
This article is part two of a series,  For Part One, Click Here.

A Case Report of Hypothalamic Dysfunction

Jim, a 34-year-old accountant, arrived in my office with symptoms of anxiety, panic attacks, chronic fatigue, and loss of libido.  Because of a low testosterone level on a blood panel, a previous physician had given Jim a Clomiphene-Stimulation Test.  This test involves a daily Clomiphene (Clomid) tablet for a week, with repeat lab testing for testosterone, LH, and FSH.  These are the hormones expected to increase after Clomiphene.   Contrary to expectations, the repeat labs showed no increase in FSH/LH, and no increase in testosterone.  Jim's previous doctors gave up in frustration.

What is The Explanation?

A failed Clomid-Stimulation Test is virtually diagnostic of hypothalamic dysfunction, representing a complex medical condition.(8)   Jim wants to know, "What is causing my hypothalamic dysfunction and chronic fatigue?"

Jim's History of Recreational Drug Use

Clubbing with Ecstasy Causes Hypothalamic Dysfunction
Clubbing on Ecstasy, dancing at nightclub. 2006. by Wikimedia Commons

Jim's symptoms started about 10 years ago while going to school in London.  On weekends, Jim went "clubbing" with his friends, dancing under the influence of recreational drugs Ecstasy and MDMA.   Jim's symptoms began shortly after this with loss of libido, anxiety, panic attacks, and chronic fatigue unrelieved by sleep.

Generation E and Hypothalamic Dysfunction (12-20)

Ecstasy (MDMA) is a chemically modified amphetamine that floods the brain with serotonin and dopamine, the two major neurotransmitters.  This produces an intensely pleasurable effect, with 800% increase in cortisol levels on the dance floor while "clubbing" on Ecstasy.(18) Long-term MDMA use shows damage to the serotonergic terminal-axonal nerves in the hypothalamus. (14-16) These important nerve axons are responsible for pituitary signalling, which controls endocrine function.   This damage may not be reversible.(5,12-20)

The Agony of Ecstasy

MDMA Ecstasy Causes Low Testosterone and Chronic Fatigue
Ecstasy (MDMA) Tablets by DEA and WIkimedia Commons

Animal studies show that hypothalamic-gonadotropin levels are suppressed in the context of low testosterone suggesting that the hypothalamic- neurosecretory system "is a primary target" of inhibition by MDMA usage.(24)  Examination of brain photomicrographs of monkeys given MDMA reveals loss of serotonergic axons in the hypothalamus, with abnormalities persisting for years. (25)  This explains Jim's Clomiphene-Stimulation Test failure.  His hypothalamic-serotonergic axons had been damaged and were unable to stimulate LH/FSH production by the pituitary gland.

Generation E

Years of weekend "clubbing" and "raves" with the recreational drug Ecstasy has created "Generation E".(12-20).  Jim is one of thousands of Generation E members now suffering from low testosterone and chronic fatigue from drug-induced hypothalmic dysfunction. 

Long-Term SSRI Antidepressants and Hypothalamic Damage

As noted by Michael H. Baumann in the January 2007 issue of Psychopharmacology, SSRI antidepressants such as Prozac, Paxil, Zoloft, Celexa, Effexor, paroxetine, sertraline, etc, may induce hypothalamic damage reminiscent of the drug MDMA(20).

MDMA, the Turbo SSRI

The drug, Ecstasy (MDMA), has been described by some as "a turbo SSRI". (13)  MDMA has more potent immediate and long-term effects than the SSRI antidepressants. Nonetheless, long-term SSRI-antidepressant use may induce the same chronic brain changes as those found with MDMA usage.(20)  There are millions on these drugs suffering a similar form of hypothalamic dysfunction.

The reality is that many commonly prescribed pharmaceuticals cause hypothalamic dysfunction.  In addition to the SSRI antidepressants, this list includes opiates, alcohol abuse, anti-psychotics, and even inhaled or topical corticosteroids.  There are many others.(21) (8)

Burnout from Psycho-Active Poly-Pharmacy

In my office practice, we will frequently see patients on multiple psychoactive drugs prescribed by the primary-care physician, internist, or psychiatrist. Psychoactive-Polypharmacy is a perfect example of an abusive medical practice that should be halted, and reveals a medical system gone wrong.   Many of these unfortunate victims are on combinations of drugs such as SSRI antidepressants, amphetamines, Vyvanse, lisdexamfetamine, Adderal, Ritalin, and benzodiazapines (Xanax, Klonopin) and narcotics such as Oxycontin and Vicodin, etc.  Some are also chronic alcohol abusers.

These patients arrive at my door with a form of "Burn Out", and drug-induced hypothalamic dysfunction characterized by chronic fatigue unrelieved by sleep.   Recovery requires a gradually tapering to "wean off" the psycho-active drug in order to minimize withdrawal effects.  In some cases, a drug-rehabilitation facility is required during the drug withdrawal phase.

Treatment of Hypothalamic Dysfunction
Hypothalamic dysfunction requires treatments described by Jacob Teitelbaum MD (22) and Kent Holtorf MD (1-4) in their excellent books and articles covering chronic fatigue and hypothalamic dysfunction.(1-4, 22)

HCG and Gonadal-Axis Treatment 

In patients with hypothalamic dysfunction and normal testicular function, an LH analog called HCG (human-chorionic gonadotropin) is usually successful restoring normal testosterone levels.   HCG stimulates testicular production of testosterone without impairing fertility, and is therefore a preferred treatment in the younger age group.

Jim's Treatment Program

Shortly after starting the HCG injections, Jim reported an immediate improvement in mood, energy, and libido.  Repeat labs showed a rising testosterone level of 687 ng/dl. To address the adrenal fatigue, Jim's treatment program also included 15-mg hydrocortisone and 50-mcg Florinef daily as mentioned by Kent Holtorf MD.(1-2)  A small dosage of natural thyroid and additional treatment protocols as outlined by Jacob Teitelbaum MD were also given (22).

Jeffrey Dach MD

Articles with related interest:

This is part two of a series; for Part One Click Here.

Low Testosterone From Pain Pills by Jeffrey Dach MD

Dr John Crisler on HCG for Symptoms of Low Testosterone

Low Testosterone Diagnosis and Treatment by Jeffrey Dach MD

More articles on Low Testosterone, Diagnosis and Treatment

Click Here for excellent discussion of pathophysiology of hypothalamic-pituitary axis.

Jeffrey Dach MD
7450 Griffin Road, Suite 190
Davie, Fl 33314

Links and References

Hypothalamic Dysfunction- chronic fatigue, low T, Adrenal fatigue, Low thyroid

Holtorf, Kent. "Diagnosis and Treatment of Hypothalamic-Pituitary-Adrenal (HPA) Axis Dysfunction in Patients with Chronic Fatigue Syndrome (CFS) and Fibromyalgia (FM)." JOURNAL OF CHRONIC FATIGUE SYNDROME 14.3 (2008).
Treating chronic fatigue syndrome and Fibromyalgia BY KENT HOLTORF, MD

3) Naturopathic Approach to Adrenal Dysfunction.pdf
The Naturopathic Approach to Adrenal Dysfunction by Jason Barker, ND and Chris Meletis, ND Townsend Letter Feb March 2005

Overnight Metyrapone Test - Clin Endocrinol (Oxf). 1994 May;40(5):603-9. The overnight single-dose metyrapone test is a simple and reliable index of the hypothalamic-pituitary-adrenal axis. Fiad TM, Kirby JM, Cunningham SK, McKenna TJ. Source Department of Endocrinology and Diabetes Mellitus, St Vincent's Hospital, Dublin, Ireland.


Ann NY A cad Sci. 1998 May 1;840:684-97.
Evidence for and pathophysiologic implications of hypothalamic-pituitary-adrenal axis dysregulation in fibromyalgia and chronic fatigue syndrome. Demitrack MA, Crofford LJ. Source Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana 46285, USA.

Endocrine Reviews April 1, 2003 vol. 24 no. 2 236-252
The Neuroendocrinology of Chronic Fatigue Syndrome
A. J. Cleare, Section of Neurobiology of Mood Disorders, Division of Psychological Medicine, The Institute of Psychiatry, 103 Denmark Hill, London SE5 8AZ,

Neuropsychobiology. 2007;55(2):112-20. Epub 2007 Jun 27.
Hypothalamic-pituitary-adrenal axis function in chronic fatigue syndrome. Van Den Eede F, Moorkens G, Van Houdenhove B, Cosyns P, Claes SJ. Source Department of Psychiatry, University Hospital Antwerp, Edegem, Belgium.

Comment by Eugene Shippen MD -- September 19, 2008 09:12 AM

Male Gonadal Disorders (Testicular Disorders & Clinical Conferences) Dale Childress, MD Monday, December 6, 2010, 8:00-8:50am Written by: Jeffrey R. Gingrich, M.D.

Guay AT, Bansal S, Hodge MB Section of Endocrinology, Lahey Clinic Medical Center, Burlington, Massachusetts. Urology [1991, 38(4):317-322] f sexual dysfunction in this group of patients.

11) /Clomiphene_increases_free_testosterone_levels_in_men_with_both_secondary_hypogonadism_and_erectile_dysfunction

Int J Impot Res. 2003 Jun;15(3):156-65.
Clomiphene increases free testosterone levels in men with both secondary hypogonadism and erectile dysfunction: who does and does not benefit? Guay AT, Jacobson J, Perez JB, Hodge MB, Velasquez E. Source Center for Sexual Function (Endocrinology), Peabody, Massachusetts 01960, USA.

Class A clubbing drugs: your children are taking them and they're here to stay By Damian Thompson Health and lifestyle Last updated: May 29th, 2012

MDMA is like a turbo SSRI -- it doesn't just block the transporter, it! reverses the process and floods the!brain with!serotonin. It also works on dopamine levels, which accounts for the energy and stimulation."


Pharmacol Biochem Behav. 2002 Apr;71(4):837-44.
Recreational Ecstasy/MDMA, the serotonin syndrome, and serotonergic neurotoxicity. Parrott AC.Department of Psychology, University of East London, E15 4LZ, London, UK. a.c.

Pharmacol Sci. 2008 Jan;106(1):2-8. Epub 2008 Jan 16.
Neuropsychotoxicity of abused drugs: molecular and neural mechanisms of neuropsychotoxicity induced by methamphetamine, 3,4-methylenedioxymethamphetamine (ecstasy), and 5-methoxy-N,N-diisopropyltryptamine (foxy). Nakagawa T, Kaneko S. Source Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto, Japan.

Dialogues Clin Neurosci. 2009 September; 11(3): 305--317.
Neurotoxicity of drugs of abuse - the case of methylenedioxy amphetamines (MDMA, ecstasy ), and amphetamines by Euphrosyne Gouzoulis-Mayfrank, Department of Psychiatry and Psychotherapy, University of Cologne, Germany;and Joerg Daumann, Department of Psychiatry and Psychotherapy, University of Cologne, Germany; LVR Clinics of Cologne, Cologne, Germany;


J Neurol Neurosurg Psychiatry. 2012 Jan;83(1):83-5. doi: 10.1136/jnnp.2010.228387. Epub 2011 Mar 28.

Preliminary evidence of hippocampal damage in chronic users of ecstasy. den Hollander B, Schouw M, Groot P, Huisman H, Caan M, Barkhof F, Reneman L. Source Graduate School of Neurosciences, Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands.

Neuropsychobiology. 2009 November; 60(3-4): 148--158.
Cortisol and 3,4-Methylenedioxymethamphetamine: Neurohormonal Aspects of Bioenergetic Stress in Ecstasy Users A.C. Parrott

The Ecstasy Generation - Slowly but surely, Ecstasy is becoming the drug of choice for the millennial era. Is it just the ultimate party high, or a postmodern cure that eases spiritual emptiness, rancorous individualism, alienation and lack of community? February 12, 2001

P sychopharmacology (Berl). 2007 January; 189(4): 407--424.
Published online 2006 March 16.  (MDMA) neurotoxicity in rats: a reappraisal of past and present findings  by Michael H. Baumann,  Xiaoying Wang, and Richard B. Rothman Clinical Psychopharmacology Section, Intramural Research Program (IRP), National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), 5500 Nathan Shock Drive, Baltimore, MD 21224 USA Michael H. Baumann

21) (full pdf file)
Pituitary. 2008;11(2):219-29. Drugs and HPA axis. by Ambrogio AG, Pecori Giraldi F, Cavagnini F.
Istituto Auxologico Italiano, Ospedale San Luca, IRCCS, University of Milan, Milan, Italy. 

Teitelbaum, Jacob. "Effective treatment of chronic fatigue syndrome." Integrative Medicine 4.4 (2005): 23-29.

Neuroendocrinology. 2008;88(2):95-102. The recreational drug ecstasy disrupts the hypothalamic-pituitary-gonadal reproductive axis in adult male rats. Dickerson SM, Walker DM, Reveron ME, Duvauchelle CL, Gore AC. Division of Pharmacology and Toxicology, The University of Texas at Austin

J Neurosci. 1999 Jun 15;19(12):5096-107.
Altered serotonin innervation patterns in the forebrain of monkeys treated with (+/-)3,4-methylenedioxymethamphetamine seven years previously: factors influencing abnormal recovery. by Hatzidimitriou G, McCann UD, Ricaurte GA.Department of Neurology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA.

Link to original article: Click Here

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Jeffrey Dach MD is a physician and author of three books, Natural Medicine 101, and Bioidentical Hormones 101, and Heart Book all available on Amazon, or as a free e-book on his web sites. Dr. Dach is founder and chief medical officer of (more...)

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