How Hormone Imbalance Can Cause Depression

How Symptoms Tell the Story of Hormone Imbalance
An Interview with Robert Gottesman, M.D.

Robert Gottesman, M.D. is now retired from his 30 years as a family practice physician. He was among the first to use natural hormones as recommended by Dr. John Lee and provided many insights to the readers of the John R. Lee, M.D. Medical Letter in the years it was published. One of Dr. Gottesman's most important messages to women and men is that there is no single formula for balancing hormones—each person's solutions are a little bit different. We spoke to him about depression and estrogen dominance, Dr. Lee's term for an excess of estrogen caused not necessarily by high levels of estrogen, but by a progesterone deficiency that leaves estrogen without the balancing effect of progesterone.

JLML: Dr. Gottesman, what do you rely on to make a decision about how to treat a woman who comes to you complaining of a wide variety of symptoms?

RG: There was an interesting British study that showed that 75 percent of the information that leads to a correct diagnosis comes from taking a detailed history. After that, ten percent comes from a physical exam, five percent from routine tests and five percent more from more invasive, sophisticated and costly tests, and in five percent you never find the answers. This has certainly been my experience, that at least 75 percent of what I need to know comes out of a detailed interview—a conversation, if you will.

JLML: Have you found any patterns emerging that point to estrogen dominance?

RG: To evaluate this, I tend to look at three or four basic areas: fluid changes, mood changes, shifts in the menses and the context in which all of this is happening. The fluid shifts I inquire about are predominantly related to fluid retention: puffiness, bloatedness, headaches, breast tenderness, and swelling of the feet or hands. I look for shifts that are out of proportion to a patient's ordinary fluctuations, something aberrant. Of course, I look at the context that might account for a shift in the hormonal status such as peri- menopause, initiation of hormone replacement therapy, a hysterectomy, postpartum, severe emotional or psychological stress, to help build a case for a hormonal cause of the fluid disturbance.

JLML: So headaches would be a symptom of fluid retention?

RG: Yes, frequently. They seem to be a very consistent symptom of estrogen dominance. I am not sure of the precise pathophysiology of headaches in this context. It may be, for instance, related to estrogen's vasodilatory effects, but they frequently occur together with some of the other signs of fluid accumulation.

JLML: What can you say about mood changes in an estrogen dominant woman?

RG: What I find a lot of is “agitated depression” which is ordinary depressive elements combined with elements of excitation or agitation. In severe cases women report that they want to jump out of their skin. They describe a sort of a restlessness and irritability about it all. And this is compounded invariably by a significant degree of insomnia. That's the way I think of estrogens, as excitotoxins, when they are excessive or out of balance. In fact I tend to think of estrogen dominance as mild estrogen toxicity. Women sometimes describe it as feeling like they have an electrical charge in their body.

JLML: And then they throw a diet soda in the mix that contains that other excitotoxin, aspartame, they're really jumping out of their skin.

RG: Large doses of estrogen given to rats makes them run compulsively — sometimes 30 miles a day.

JLML: So here you have a hormone that tends to create passivity, but also creates agitation.

RG: Yes, that is why I called that particular symptom “agitated depression.” I don't typically see the estrogen dominate women coming in with just ordinary symptoms of depression. This is more of a hyper or anxious depression. It has been helpful for me to learn from my more extreme cases so that I can recognize the syndrome in its milder forms. Just today I saw a woman with what started as a postpartum depression two and a half years ago. She was depressed, anxious, and she intuitively felt that her symptoms were hormonal. Her doctors gave her Premarin which exacerbated her symptoms and so they then added an antidepressant. For the past two and a half years she would go to bed at 11 p.m., struggle to sleep by about at 3 a.m., have a fitful sleep and get up at 7. I recognized her symptom complex which included headaches, and sore breasts, as estrogen dominance. I advised her to stop her estrogen (in a tapering schedule) and prescribed some progesterone cream. After two days of progesterone cream she slept restfully from 11 to 7 without waking up. Also now she's able to take naps with her son, which is the first time she's ever been able to do that. That's an extreme example, but it's also rather representative.

An even more extreme case was a woman I saw who clearly had a shift of her hormonal status fourteen years ago, just following her hysterectomy when she was put on Premarin. She knew something was different, and she started to develop insomnia. Then she developed a sort of nervous agitation, and then she became depressed. She went to sleep centers, and they found out that even when she was sleeping she was awake — her brain rhythm was still in alpha. The first time I gave her some progesterone she slept until noon, and that was only 1/8 of a teaspoon of a 1.5% cream. About a month later she got off of her antidepressant, too.

JLML: Are there some physical signs you can see right away when a woman walks in your door?

RG: What I frequently see is a woman with a puffy, reddish face, particularly around the cheeks. It looks almost like a sunburn. I certainly see people who are estrogen toxic or estrogen dominant who don't have that, but when I see it, it's another suggestive sign.

Another pattern I look at are the menstrual cycles themselves. A premenopausal woman who is still menstruating can clearly still be estrogen dominant. What I've noticed is that the period's cycle length often starts to wander. It varies. It's not regular like it used to be. The period also doesn't start and stop as cleanly as it used to. It seems that progesterone cleaves the endometrium more cleanly so that the menses starts and stops more regularly.

JLML: Do you have any insights about how to gauge the best dose of progesterone?

RG: I think it's best to begin with a physiological dose, such as 15 mg twice a day, and if that doesn't help, increase to 25 mg twice per day and once in awhile for the unusual case, 50 mg twice a day. But more progesterone is frequently not better. In almost all biological systems, one is almost always looking for optima. Not necessarily more is better. Sometimes the maxima may be an optimum, but most frequently the curve is U-shaped or an inverted U. The down-regulation of progesterone receptors may be a real phenomenon with excessive progesterone. That means that if it has worked very well and then after several months it starts to not work as well, you want to go down on the dose, not up (particularly if you are using more than physiological doses).

JLML: What clues does a woman have, to know when her hormones are out of balance? For example, if her premenstrual sore breasts come back, should she back off on the dose?

RG: She should back off on the dose and see what happens during her next cycle. But this may also be an indication to look elsewhere. We don't want to get tunnel vision here. The problem may be thyroid, or dietary or strictly emotional. Most typically, in my experience, symptoms arise with a combination of several imbalances. So I work with the hormones, but then I also look elsewhere. Today I saw a patient who only has a bowel movement every four days and she's suffering from depression. She's gotten vastly better on the progesterone, but now we're working with her diet.

This interview was originally published in the John R. Lee, M.D. Medical Letter. Although the Medical Letter is no longer being published, you'll find many of its articles on this website.

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