Men (and some women) joke all the time about women “going crazy” pre-menstrually or at other times when our hormones are fluctuating, and while I don’t particularly like the idea of describing what happens to us as “going crazy,” science shows that there is some truth to the idea: the time periods when women’s hormones fluctuate tend to be associated with increased risk of mental health concerns. It’s common knowledge that anxiety and depression are associated with menstruation [pre-menstrual syndrome (PMS) and pre-menstrual dysphoric disorder (PMDD)], with pregnancy (post-partum anxiety and post-partum depression), and with menopause (post-menopausal anxiety and depression). Many people don’t realize, though, that reproductive hormones, mainly estrogen, are also strongly associated with other mental health concerns such as bipolar disorder and psychosis and that, in many cases, addressing the problems related to the reproductive hormones actually leads to a resolution of the psychiatric symptoms.
Estrogen, Depression, and Bipolar Disorder
We don’t fully understand the role that estrogen plays in depression and bipolar disorder, but we do know that it plays a significant role. You probably know that in the post-partum period, the risk of being diagnosed with depression significantly increases. Well, the risk of being diagnosed with bipolar disorder and the risk of an exacerbation of symptoms related to bipolar disorder dramatically increases as well. In fact, one large-scale study involving over 1100 women and over 600 men estimated that women diagnosed with bipolar disorder are more than 23 times more likely to be admitted for reasons related to their bipolar disorder (e.g. depression, mania, etc.) during the first month after childbirth than during their actual pregnancy.
When we understand that estrogen levels increase in pregnancy and then dramatically decrease after childbirth, then it makes sense that the fluctuation in hormones may be causing or at least a contributing to the new mothers’ hospitalizations.
Not only does this happen after pregnancy, but it also happens in other stages when women’s estrogen levels dramatically decrease, such as menopause. Because the peri- and post-menopausal periods are known to be associated with mood changes, researchers wanted to explore the effects of these periods on bipolar disorder in women who carried this diagnosis. What they found was that menopause was associated with increased bipolar symptoms overall and particularly with an increase in depressive symptoms.
But is it Only Estrogen?
Estrogen isn’t the only hormone that can affect mental health. Other hormonal conditions such as polycystic ovarian syndrome (PCOS), which is characterized by elevations in a hormone produced in the adrenal gland called dehydroepiandrosterone sulfate (DHEA-S) and elevations in testosterone or testosterone-related symptoms can also lead to serious psychiatric symptoms that very closely resemble bipolar disorder with or without psychotic features. PCOS is the most common endocrine problem in women of reproductive age, and yet women with psychiatric symptoms that are most likely being caused by their hormonal conditions are mistakenly diagnosed with and sometimes inappropriately medicated for psychiatric conditions. Because symptoms don’t improve on the medication, they are prescribed stronger and stronger medication leading to more symptoms that then have to be managed with more medications. Here’s an interesting case study regarding PCOS and bipolar disorder: PCOS Case.
Hormonal Disorder or Mood Disorder: Why All the Confusion?
Hormonal disorders and mood disorders can share many symptoms and it can be somewhat difficult to tell them apart, even for doctors and psychiatrists. It is far more common than we would like to admit for women who are actually experiencing hormonal mood changes to be misdiagnosed with depression or bipolar disorder. What’s the reason for this confusion? It is the fact that the hormonal changes that take place after ovulation, most notably a dramatic decrease in estrogen, are frequently accompanied by depression or cyclical mood changes such as are seen in bipolar disorder.
While hormonal testing can be helpful in determining if hormonal levels are simply declining or if they have actually fallen to lower than normal levels, the hormone levels of many women with mood disorders and those with hormonal disorders can actually be very similar. Because hormone levels may appear “normal” when tested, it’s easy to overlook a hormonal disorder that may be contributing to mood changes.
You may be wondering how a condition could be due to “low” estrogen (more accurately, fluctuations in estrogen) without estrogen showing up as low on blood work. Well, first of all, the range for normal estrogen levels is very broad. The reference range varies by labs, but can range from 43.8 to 211.0pg/ml during the period of time between ovulation and menstruation (known as the luteal phase). Because the range is so wide, decreases in estrogen levels can be dramatic, even if estrogen levels never leave the normal range.
Secondarily, while research does support the fact that low estrogen can result in mood disorders, other research demonstrates that the problem in many women diagnosed with bipolar disorder may not be with the estrogen level itself. Instead, the problem is with the women’s response to estrogen. Some women have a genetic abnormality that makes them more susceptible to mood changes such as are common in bipolar disorder when their bodies are experiencing fluctuations in estrogen levels. Research suggests that these women may be more vulnerable to fluctuating estrogen levels, which may then act as a triggering factor for bipolar disorder.
Hormonal Disorder or Mood Disorder: How to Tell the Difference
Because lab results can be very similar in women with hormonal disorders and women with mood disorders, making the diagnosis of a hormonal disorder vs. depression or bipolar disorder relies heavily upon the symptoms of each woman. Here is a list of things that women whose mood changes are actually due to hormonal disorders frequently report:
- Mild to severe cyclical mood and/or behavioral changes with menstruation as a teenager
- Other premenstrual concerns such as menstrual migraines, bloating, or breast tenderness
- Anywhere from 5 to 20 “good days” per month
- A deep feeling or belief that their health concerns may be related to their hormonal status
- Relief from symptoms of depression and other mood changes during pregnancy (when estrogen levels are high and don’t fluctuate cyclically)
- Depression or other mood changes that started or returned after childbirth (when estrogen levels declined again and menstrual cycles returned)
- Pre-menstrual mood changes worsened with age and when menstrual cycles completely ceased (e.g. menopause, hysterectomy with oophorectomy), mood changes stopped being cyclical and became more or less constant
- Lack of or minimal response to medication prescribed for depression and/or bipolar disorder
When Psychiatric Medication is Definitely Not the Answer
In cases where the cause of the mood changes is hormonal, there tends to be a very minimal (if any at all) response to the medication that’s typically prescribed for depression and for bipolar disorder. This is because, instead of being a problem with serotonin, dopamine, or other neurotransmitters, the problem is with the woman’s response to fluctuations in estrogen levels. When the appropriate diagnosis is not made, the result tends to be years of inappropriate drug therapy including anti-depressants, mood stabilizers, anti-psychotic medication, and anti-convulsants or seizure medication, without noticing any real improvement.
That Makes Sense for Depression, but What About Mania and Hypomania?
Research shows that modulating reproductive hormones can help reduce symptoms of mania as well as depression. Four studies looked at participants with bipolar disorder who were all in acutely manic or hypomanic states and their response to the drug Tamoxifen, a chemotherapeutic drug that induces estrogen production in the ovaries of pre-menopausal women. Study participants were given either Tamoxifen or placebo and all other variables were kept constant. Participants who were given Tamoxifen had higher levels of serum estrogen at the end of the trial. At the end of these studies, researchers successfully demonstrated that Tamoxifen had significantly reduced symptoms of mania in participants who were given this drug.
Because Tamoxifen is also what is known as a PKC inhibitor (lithium and valproate also have these properties), researchers wanted to know if it was Tamoxifen’s PKC inhibition or its effect on estrogen that made the difference in resolving mania. To help find the answer, they took a closer look at one of the studies where women were given Tamoxifen, medroxyprogesterone (another supportive hormonal agent), or placebo. This study showed that Tamoxifen significantly reduced symptoms of mania and hypomania and medroxyprogesterone did as well (to a lesser degree than Tamoxifen, but more than placebo). The fact that medroxyprogesterone modulates hormonal status but is not a PKC inhibitor suggested that it may have been Tamoxifen’s effect on hormonal status that led to the reduction in manic and hypomanic symptoms and not its PKC inhibition.
But this research wasn’t convincing enough, so researchers also looked at cases where women with bipolar disorder were given estrogen. In these studies, women diagnosed with bipolar disorder who were experiencing post-partum psychosis were found to have low-normal or abnormally low estrogen levels. These women were given estradiol to increase their estrogen levels. At the end of these studies, researchers found that the women who stuck with the estrogen therapy recovered from their psychosis, but those who dropped out of the study early relapsed with psychotic symptoms within a week of discontinuing. These studies lent strong support to the belief that Tamoxifen’s effect on bipolar disorder is likely attributable to its effect on estrogen.
Bio-identical Hormone Replacement Therapy (BHRT) for Bipolar Disorder?
In light of this research, some people consider hormone replacement therapy in an attempt to limit the fluctuations in hormones that result in the mood changes we’ve discussed. Although some do opt for BHRT, many of my patients are skeptical of the long-term effects associated with introducing exogenous hormones into the body. I wont go into the details here, but Harvard Health has a pretty extensive article delineating the risks and benefits, as well as the history of bio-identical hormone replacement therapy.
If you believe that a hormonal imbalance may be contributing to your mental health concerns, but you are concerned about the risks associated with BHRT, there is still hope of modulating your hormones. As you’ve likely read before if you frequently read my blog posts, I’m a strong advocate for the therapeutic order, meaning that I believe in using the least invasive methods of treatments first and then moving on to a more invasive treatment option only if the less invasive, more natural options are unsuccessful in a particular case. The research shows that there is a wide variety of natural substances that are effective in modulating reproductive hormones without the added risks of vitamin and mineral depletion and cancer that are involved with more invasive options. I’ve seen very good results in modulating my patients’ hormones using these natural treatment options and can attest to the fact that it’s possible to modulate hormones using them if you understand how they work (their mechanism of action) and when to use which.
If you’d like to work with a doctor who is willing to help you uncover the underlying cause of your mood dysregulation, whether it be reproductive hormones, other hormones, genetic factors, or something else so you can start feeling like yourself again, call my office and schedule a complementary, no-obligation consultation where we can talk about your health concerns and see if we are a good fit for each other. -Dr. Janelle Louis ND