Hormone Imbalance, Not Bipolar Disorder

Over the past several decades, psychiatric diagnostic acumen has improved. Diagnostic accuracy has not followed suit. More and more people carry psychiatric diagnoses which are inaccurate and have very negative consequences for their lives. Arguably the most frequent, popular and incorrect diagnose is bipolar disorder (BP), in all of its sundry subtypes and flavors. It seems that anyone who is moody, angry, temperamental, objectionable, or who objects to something is bipolar. And the proof is in the treatment. Load them up with cocktails of Seroquel, Depakote, Abilify, Lithium, SSRIs, Klonopin and Trazadone, and, as they become fat and dopey, they are no longer sassy. Proof is in the pudding, what?

No, the proof is not in the pudding, or the metabolic syndrome and tardive dyskinesia and sexual dysfunction which encumbers these folks. All that is proven is that one can be obliterated by these cocktails but being zonked by them doesn’t prove bipolarity. Many of these unfortunates, whom I shan’t address today, have ADHD, anxiety/panic disorders, epilepsy, personality disorders, drug abuse problems and bad attitudes. Some just don’t go with the flow so, obviously, there must be something wrong with them. Not.

I now have a sufficient database to report that a significant subset of BP patients are not BP at all but have gonadal hormone problems. Correct identification and treatment of these imbalances stabilize the patients and refute the purported BP (although I do not know how to get the incorrect diagnoses out of insurance records and undo the damage to these people's lives). This occurs in men and women.

Ladies first: There are two subgroups here; really, really bad PMS and really, really bad PMS in conjunction with Stein-Leventhal Syndrome (PCOS: polycystic ovary syndrome).

Most of these women are diagnosed at relatively early ages, but after menarche. Indeed they have florid mood swings, affective dysregulation, depression, impulsivity, suicidal gestures ... the whole gamut. True psychotic symptoms are rare. And yes, they come to me on one of the cocktails du jour. Many do meet criteria for ADHD and PLMD (periodic limb movement disorder) but these have always been subordinate to the horrible, rapid cycling BP.

Careful history, often with input from parents, partners or spouses reveals—here’s the surprise—that the patient’s cycling correlates closely with her menstrual cycle. In fact, that’s when her BP is harder to control. My impression then becomes, "Hmm."

I won’t go into a discussion of hormone cycling, enzymes and neurotransmitters now, but will put some references at the end. In short, after careful evaluation and consideration, I detoxify these women from their toxic cocktails. It is difficult and often frightening. But once SSRIs and dopamine blocking agents are gone, the super-sensitization of the dopamine pathways have cooled-off a tailored titration onto a pulse pattern of Wellbutrin controls the PMS and BP disappears. Imagine that!

No, every woman diagnosed with BP who has PMS does not fit this paradigm, just many of them. Something to consider.

The women with PCOS and BP often haven’t been diagnosed with PCOS yet. Some have. PCOS is characterized by irregular, painful menses, elevated testosterone, masculinization, hirsutism, weight gain and many other features in varying degree. Insulin resistance and Diabetes Mellitus is common. In the patients, they may have significant internal hormone fluctuations without the manifestations of a period--menses. Thus it is necessary to get long and careful histories, keep calendars, get hormone assays at “different” times and then decide about treatment. By the bye, most medications for BP cause weight gain and some directly increase blood glucose and all of this is quite bad for a patient with PCOS.

In selected cases, the BP meds are withdrawn. The metabolic issues must be addressed; control and suppress androgens to normal female levels, control blood glucose and insulin. Then address the PMS. As noted above, this usually can be accomplished with Wellbutrin, but in some cases wherein the fluctuations are so erratic and unpredictable that a pulse pattern cannot be established effectively, Monoamine Oxidase Inhibitors (MAOIs) are used because it is the surge in MAO that occurs abruptly when a woman’s estrogen drops (and the MAO is the enzyme that degrades all biogenic amines—dopamine, serotonin, noradrenalin, et. al.) and induces the miserable moodiness and symptoms of PMS mistakenly called BP in these cases.

Now the men: this has been more subtle and took longer to clarify. Men have estrogen just as women have testosterone. Testosterone is metabolized into estrogen! I posited years ago that a subset of men are exceedingly rapid metabolizers of testosterone into estrogen (and also some may over-produce it intrinsically). A recent article in the New England Journal of Medicine confirmed my supposition.

Anyhow, I figured this one out backwards. After seeing a series of men with putative BP, on all of the usual drugs, I discerned a pattern of diminished libido, sexual dysfunction, subtle feminization and often new and strange sexual thoughts and fantasies. This was always called a medication side effect. However, evaluation of hormone levels revealed relative to absolute hypogonadism. I do not attribute the finding to the psychiatric drugs because I have also seen several men who presented with first depressive episodes and no prior treatment with the same features. And their estrogens were usually high normal or abnormal.

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But let’s stick with the BP. Finally off psych meds and on testosterone replacement, some interesting things happened. Their moodiness, irritability, insomnia, and other symptoms resolved as they were re-masculinized and estrogen levels fell. Some of the time.

A sub-group that has been most fascinating are the super fast metabolizers. When giving transdermal testosterone daily, they were feminized by immediate conversion to estrogen. This was not considered a good result by the men and their wives. Use of injectable long-acting, slow-release testosterone worked, but not in the traditional 200 mg in the tush every two weeks. After a sufficient duration of treatment (in testosterone replacement therapy, blood levels can rise swiftly in a few weeks but clinical response can take three months or more), they began to cycle again, often worse. This has been called "roid rage" from excessive testosterone but, in fact, the trouble occurred as the testosterone wore off and the estrogen rose dramatically—a sort of male PMS. At first, we addressed this by increasing frequency of injection, usually with a lower dose (100 mg each time). The result would be an individualized but predicable cycle; three to six good days followed by the crash. Yet testosterone levels were pretty even. The estrogen levels were cycling down after an injection and skyrocketed with the crash! Eureka.

These men require estrogen blockers, which I leave to my endocrinology colleagues. It is fascinating to extrapolate back and wonder how many of these men had excessive estrogen and/or rapid metabolism that precipitated both the spurious diagnosis of BP and caused the hypogonadism

Be advised, most physicians have no idea what I’m writing about. They need to catch up.