Hormone overdose: How can you tell?

By Etsuko Ueda
I often hear from post menopausal women who have been struggling trying to decide which is worse, doctor prescribed hormone regimen or menopausal symptoms. The bottom line is: If you do not feel well, something went wrong, and in most cases, it's hormone overdose. It can be estrogen overdose, progesterone overdose, or both (use of fake hormones is out of the question).

In June 2009, one person wrote me "I am 53 and have been using the Vivelle .025 patch for hot flashes and mood swings for around 5 months. Feel great, but then my doctor said I had to take the course of 12 days every 6 months of progesterone as I still have my uterus. So, I took only two days of the Prometrium 100 mg he prescribed and I got almost an allergic reaction to it, facial and eye swelling and redness and started bleeding and cramping on day two. I quit the prometrium after the second day and the bleeding lasted another full week. Also came with horrible headaches that wouldn't go away."

It is very unfortunate, although typical, that her doctor did not know progesterone cream (
20~30mg a day) can be used along with estradiol (continuous regimen) to suppress uterine lining thickening (see Hormones: Dos and Don'ts).

Another person wrote me in November 2011 "I had a total hysterectomy about 5 years ago and have been fighting problems ever since. My doctor has prescribed estradiol pill 1mg and I felt like crying all the time, so I incorporated Progesterone cream and now I’ve gained about 8 lbs in 2 weeks and have anxiety every morning. Also weird dreams. My libido has been in the toilet for years now, my poor hubby."

Three months later, after having tried what I suggested, she wrote me saying "I have used your dosages of all 3 hormones and they are perfect for me. No more hot flashes, no crying all the time, And the libido has kicked in. I can't thank you enough for your email. I have been to 3 different doctors and not one has gotten it right, this is over a period of 4 years."

These cases illustrate some important points:
  1. Most doctors are clueless or misinformed about hormone supplementation.
  2. Even a ultra low dose of estradiol 0.025~0.050mg/day patch is effective against menopausal symptoms, but stimulates uterine lining thickening if progesterone is not used along with it.
  3. High dose progesterone such as Prometrium 100 mg cause overdose problems (water retention, tired and sluggish), and many women cannot tolerate it. I tried it for 2 days and felt so terrible, that I threw it a way. Since Prometrium 100 mg is the most commonly prescribed natural progesterone and many do not feel well on it, many women end up exposing themselves to unnecessary hormone related health risks either by taking estrogen alone or by giving up on hormone supplementation all together.
  4.  If you add progesterone to estrogen overdose, things can get worse, because progesterone increases estrogen sensitivity by increasing estrogen receptors. (That's why you need to start with progesterone first and then add estradiol at the lowest dose and see if you need to increase it or not.)

How can you tell when it's too much or not enough
Since today's medical science is not advanced enough to tell exactly how supplemented hormones get distributed and used in your body, there is no hormone test you can rely on to see your dose is not enough or too much. So how you feel is the best way to tell. For practical information, see Safe & Effective Natural HRT = progesterone cream + DHEA + low dose estradiol patch.

Not enough estrogen: Vaginal atrophy or dryness is the best way to tell if your estrogen level has been enough or not, because estrogen seems just about the only thing that matters. Progesterone can make estrogen work better, but no amount of progesterone can prevent it if estrogen level is not adequate, according to my experience. Commonly, people think hot flash is the sign of menopause = low estrogen, but hot flash can happen even when estrogen is secreted enough to trigger menstruation. Foggy brain is another sign, but it can be transient. Furthermore, there are other diseases and conditions that can trigger foggy brain, hot flashes and/or night sweat. Clinically, endothelium dependent flow-mediated dilation (on-demand blood supply) becomes weaker when estrogen is low, which has profound effects on your cardiovascular health which affects the rest of the body as well (see Menopausal Symptoms And Cardiovascular Health,
Menopause and How estrogen helps bone health?)

Too much progesterone: As I pointed out in a case above, if you don't feel well (swelling and other water retention related symptoms, as well as feeling sleepy, sluggish, tired), that is a sure sign. Generally, you are safe in a range of 10~40mg /day transdermal. 100mg is too much.

  1. The most important thing to remember about progesterone overdose is this: Progesterone is known to have biphasic action on water retention and cellular calcium/magnesium ion ratio. "Biphasic action" means that some of the beneficial effects will be lost and the opposite effects may appear when you take too much progesterone.
    • Water retention and swelling is commonly reported by people who are subjected to progesterone overdose, while at a lower dose (10 to 40 mg/day) diuretic effect (facilitates urination, reduces intracellular water) has been reported. The diuretic effect is attributed to the progesterone's role in blocking mineralcorticoid, which gets lost if progesterone is lacking or overdosed resulting in water retention and swelling by increased deoxy-corticosterone, a potent mineralocorticoid, and 100mg oral dose is enough to demonstrate this effect. This water retention from a lack of progesterone or overdose is different from estrogen driven bloating which is most pronounced around abdomen, although, both can coexist.
Pharmacological and functional characterization of human mineralocorticoid and glucocorticoid receptor ligands. R Rupprecht, J M Reul, B van Steensel, D Spengler, M Soder, B Berning, F Holsboer, K Damm, 1993
    • Promotion of intra-cellular magnesium level is well known property of progesterone, while estrogen promotes intra-cellular calcium. Together, these two hormones regulate cellular calcium/magnesium ion ratio. This is the reason progesterone can be used as a calcium blocker. However, when progesterone is overdosed, it seems to lose this effect. As a result, your cells may not get enough magnesium, calcium/magnesium ion ratio may shift in favor of calcium, and you may experience something similar to estrogen dominance, which can result in various harmful effects (Sex steroid hormones exert biphasic effects on cytosolic magnesium ions in cerebral vascular smooth muscle cells: possible relationships to migraine frequency in premenstrual syndromes and stroke incidence. W Li, T Zheng, B M Altura, B T Altura, 2001). Below are some of the harmful effects:
      • The cellular activities and regeneration get amplified (uterine lining gets thicker, cancerous cells multiply faster)
      • Your brain cells get more excitable at higher level, brain seizures can get triggered more easily, and get harder to calm down.
      • Your blood vessels and intestines go into spasm more easily, triggering heart attacks and diarrheas.
      • Magnesium has been effectively used for some form of epilepsy such as eclampsia as well as ADHD and PMS. Similarly, progesterone has been shown to reduce Catamenial epilepsy and PMS, however, progesterone overdose may reduce these benefits, although I have not seen any study designed to demonstrate it.
For more information on the beneficial effects of progesterone at a proper dosage, see PMS: The Underlying mechanism, and Safe Use of Hormones: the Hard Evidence.
Progesterone related water retention is different from estrogen driven bloating, which is mediated by cystic fibrosis transmembrane conductance regulator (CFTR) (Estrogen-Induced Abnormally High Cystic Fibrosis Transmembrane Conductance Regulator Expression Results in Ovarian Hyperstimulation Syndrome. Louis Chukwuemeka Ajonuma, et. al. 2005).
  1. Progesterone and its metabolites Allopregnanolone work as GABAa mediated sedative and make you feel calm at a right dosage, but make you feel tired and sluggish, slowing down psychomotor, and digestive functions at a higher dosage. Again 100mg oral dose is enough to demonstrate this effect. (Administration of progesterone produces mild sedative-like effects in men and women. Anna H V Soderpalm, Sommer Lindsey, Robert H Purdy, Richard Hauger, Harriet de Wit, 2004; Effects of acute progesterone administration in healthy postmenopausal women and normally-cycling women. H de Wit, L Schmitt, R Purdy, R Hauger , 2001).

Not enough progesterone: Although its health consequence is serious (see Safe Use of Hormones: the Hard Evidence), our body does not seem to have a way to tell it reliably. One thing I notice when I am off progesterone is irritable bowel: fatigue and stress can trigger cramping and diarrhea too easily. Rubbing progesterone cream on abdomen can stop it almost immediately. Clinically, if you use estrogen without progesterone, your blood coagulation factors go up (your blood gets thicker and stickier, making blood clots to form easily), just like your intestines, your cardiovascular system goes into spasm more easily to trigger heart attacks (see Menopausal Symptoms And Cardiovascular Health), and your uterine lining gets thicker, which can lead to heavy bleeding, cramping, and uterine cancer. Please note that a menstruation with heavy bleeding and/or cramping is not normal at any age, and it may be a sign of low progesterone.

Skin and hair problems may also indicate not enough progesterone. In What your Doctor May Not Tell You About Menopause , John R. Lee pointed out skin problems such as acne, seborrhea, rosacea, psoriasis, and keratoses in middle age and beyond may be an indication of not enough progesterone. I personally witnessed keratoses (hard horn like growth) on a 80+ years old woman's leg disappear with progesterone cream applied directly on it. So did a polyp like growth on my neck. Hair loss may be also an indication of not enough progesterone. I personally witnessed white hair grow back on women over 80 years old with progesterone cream in 3 to 6 months.

To get the maximum benefit of progesterone, be sure to supplement magnesium about 300mg/day. Many of progesterone's biological effects are based on its ability to increase intracellular magnesium
(see PMS: The Underlying mechanism).

Too much estrogen: Estrogen is a stimulant, not just to your brain but to your entire body and some people even call it excite-toxin. Your brain becomes more excitable (less controllable). It can amplify stress hormone responses to psychosocial stress, as indicated in the following studies. It can also cause bloating and other PMS like symptoms.
Clinically, your new cell generation gets accelerated: uterine lining gets thicker, more cancerous cells gets generated, if there is not enough progesterone to control them (see What Your Doctor May Not Tell You About Breast Cancer, by John R. Lee, M.D. David Zava, Ph.D, and Virginia Hopkins, 2001).

Confusing symptoms of not enough estrogen and too much estrogen
Women who go through natural menopause transition experience symptoms associated with a volatile fluctuation of hormones: Period may skip for a few months at a time, then you may be surprised by a heavy bleeding, often progesterone is not secreted, estrogen can be extremely high or very low. Since low estrogen leads to under-active parasympathetic system and overactive sympathetic system, while too much estrogen (even with normal progesterone) can lead to hyperactive brain, both low and high estrogen may lead to similar neural instability, tension, and vulnerability to stresses.

The first thing to do during menopausal transition is to start progesterone to minimize the risk of estrogen dominance. However, starting progesterone when estrogen is very high can make the symptoms worse, since it elevates estrogen sensitivity. The logical solution is to start progesterone while estrogen is very low, that is shortly after the start of your period. However, when it is highly irregular, it may not be easy to tell when your estrogen level is low. In those cases, you might want to start progesterone very slow. Whichever the case, it may take 3 month or more to stabilize your hormones. When you start to have menopausal symptoms such as hot flashes and foggy brain, add ultra low dose of estradiol patch and/or DHEA to control the symptoms and to reduce the bone ravaging stress hormones.

Too much DHEA: As I reviewed in DHEA for Menopause, DHEA can cause skin/hair problems when overdosed. Therefore, my guideline for DHEA dosage is: if you start to have oily hair/skull or pimples, it is too much. For most people, 5 to 10mg/day (oral or transdermal) may be a safe and effective level. 

One-year therapy with 10mg/day DHEA alone or in combination with HRT in postmenopausal women: Effects on hormonal milieu.(Nicola Pluchino, et. al. 2008) seems to agree. The good news is that a long term use of DHEA strengthens the adrenal gland's capacity to produce DHEA in response to adrenocorticotropic hormone (ACTH). Therefore, you may need to lower the dosage after a while. 

For more information, See:
Menopausal symptoms: What are we complaining?
Menopausal Symptoms And Cardiovascular Health
Menopause and What Really Happens to your Bones
Hormones: Dos and Don'ts
Safe Use of Hormones: the Hard Evidence
PMS: The Underlying mechanism

Important: You probably found this page because you had questions about hormones. I hope you have found the answer you have been looking for. If you are uncertain, please note the following:

Before you post your HRT questions, please try what I think safe and effective for at least 3 months: estradiol 0.025~0.050mg/day patch, with 20~40mg/day progesterone cream (about 1000mg progesterone in 2oz cream). You can also add DHEA 5~10mg /day.

That is the only recommendation you will get from me.