Estrogen interactions

There are not a huge number of things that interact with estrogen, but there are enough of them that you should be aware of them. In many cases, information on estrogen interactions comes as concerns raised about hormonal contraceptives. This is more researched just because of the rather dramatic (and generally perceived as undesirable) result of contraception failure. But these same precautions would also apply to estrogen HRTs, even though they might be to a lesser (dose-related) extent. So don't be misled when you see OCPs listed but not HRTs—if it affects estrogen in one setting, it probably does in all.

Smoking and alcohol are the really well known ones, and we've dealt with those in the discussion on dose amounts. But there are a few others that are noteworthy.

Saint John's wort

The popular herbal antidepressant St. John's wort is one that is often combined with HRT. As it turns out, SJW interferes with the action of ovarian and adrenal hormones via a particular metabolic pathway they share. SJW is not alone in this effect, however. A letter in the medical journal Lancet in 1999 said this about it:
While recent studies indicate that St John's wort (Hypericum perforatum) may potentiate certain sub-enzymes of the cytochrome P450 enzyme system, it should be noted that several common foods and drinks also influence parts of this same enzyme system. It is well documented that grapefruit juice is a potent inhibitor of cytochome P450. Conversely, cruciferous vegetables such as broccoli, cabbage, and Brussels sprouts are P450 inducers. Similarly, charcoal-grilled beef, red wine, ethanol, and cigarette smoke also induce the cytochrome P450 system and have the potential to alter the rate at which many drugs are metabolised.
This is not a reason to avoid any of these foods, particularly, nor is it a reason to avoid the use of SJW. But the implications for users of HRT can be summarized as a need for caution and awareness when combining SJW or these other foods with HRT, whether conventional hormones or alternative. If you have become balanced on your HRT, either beginning or stopping the use of SJW can cause your hormone levels to fluctuate even though you do not change the HRT dose. If SJW lowers the effectiveness of HRT (the direction the studies and anecdotal data would suggest), then adding it to your regimen could make it seem as though you are estrogen-deficient, and stopping it could make you estrogen-overloaded. These are not reasons not to use SJW, but are certainly reasons why you need to take this effect into consideration in its use.

In 2010 a study came out that indicated that "St. John's wort may cool hot flashes" (unfortunately the journal in which this is published is behind a paywall; the link is to a news release). The small, short study indicates that SJW performs better than placebo at reducing the quantity and severity of hot flashes. One possible cause cited for this effect is that SJW contains phytoestrogens. We'd not seen this herb included in phytoestrogen lists before, but that raises the question as to whether SJW can be considered a safe approach for women with estrogen-mediated cancers or endometriosis or other women who are seeking to limit their exposure to hormones. There is only skimpy data about this premise so far, but it should remain a concern until evidence exists to rule that possibility out.


A number of women are concerned about the interaction of hormones and antibiotics. We've searched long and hard and not been able to turn up anything more than this definitive maybe (referencing oral contraceptives, but hormones is hormones) by Weaver & Glasier of Edinburgh Healthcare National Health Service Trust, Family Planning & Woman Services, Scotland that was published in Contraception 1999 Feb;59(2):71-8:
There is considerable variation in opinion about the importance of drug interactions between the combined oral contraceptive pill (COCP) and broad-spectrum antibiotics. Clinical practice varies widely, especially between doctors in Europe and those in the US. Rifampicin and griseofulvin induce hepatic enzymes and do appear to have a genuine interaction with the COCP, leading to reduced efficacy. The situation with the broad-spectrum antibiotics is less clear. There are relatively few prospective studies of the pharmacokinetics of concurrent COCP and antibiotic use and few, if any, demonstrate a convincing basis for any reduced contraceptive efficacy. There is evidence, however, that variable contraceptive steroid handling could make some women, at some times, more susceptible to COCP failure.
We also found this information summary more recently in a hormone prescription information sheet:
In vitro and in vivo studies have shown that estrogens are metabolized partially by cytochrome P450 3A4 (CYP3A4). Therefore, inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism. Inducers of CYP3A4 such as St. John's Wort preparations (Hypericum perforatum), phenobarbital, carbamazepine, and rifampin may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects... Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice may increase plasma concentrations of estrogens and may result in side effects.
If anything, the functional implications are to be sure your doctor and pharmacist know everything you're taking (ask—don't assume) and then to be prepared to weather the shift in your HRT coverage if it feels like you're falling short. Nothing we found indicates that hormones diminish the effectiveness of antibiotics or cause any deleterious interactions in that direction. You should also bear in mind that the stresses of illness and the chemical warfare of treating them may redirect some of your progesterone for cortisol production, thus putting your hormone balance a bit off as well. In general, it doesn't make sense to adjust HRT doses to cover this sort of temporary disruption; really, it's just something to be aware of so we don't think our HRT has suddenly somehow stopped working properly.


Stress, as noted above, can come into play as a balance disruptor when we're ill. But there are lots more stresses in our lives, and our bodies don't distinguish one from another in hormonal response. It's also important to remember that good things can be stressors as well as bad: a vacation, moving into a new home, getting married, even something unanticipated like a surprise birthday party can give us a bit of a whack with stress. Again, though, it's more something we need to simply wait out than try to adjust our hrt to compensate for.

Other herbs and foods

We've mentioned elsewhere that phytoestrogens in foods and xenoestrogens we consume from foods or environmental contamination can sort of act like estrogen at the same time that they can block estrogen's full actions. Sunscreen (free signup required to read) may contain estrogenic substances as well. 

One that we recently learned about is kelp. It's believed that because consumption of kelp reduces cholesterol, it may limit the available resources for production of our adrenal estrogens. It has been demonstrated in rats and human tissue samples that it both lowered circulating levels of estradiol and exhibited binding to both estrogen and progesterone receptors. In that many sites advise intake of kelp as an anti-estrogenic measure to reduce breast cancer or fibroids, we need to remember that this comes at the cost of reducing our hrt efficacy. It doesn't really make sense to take an hrt at the same time we're taking something that directly competes with it, does it? So, not really a strategy for women in surgical menopause. Small amounts of kelp consumption are probably not a major disruptor, however, and we most likely don't need to give up our sushi in the interests of hormonal stability.


And there's one last caution that is important to a lot of us, and that's with respect to thyroid supplements. Lots of postmenopausal women are or become hypothyroid and need to take one or another of the thyroid hormones. These are notoriously persnickety about what is taken with them, to the extent that the safest approach is to take them absolutely alone, with neither food nor drink. While references do not specifically cite hormones as interfering, it's a whole lot safer to maintain the habit of taking thyroid alone and to schedule your HRT for other times (at least an hour apart). We make no claims of being particularly well-researched on thyroid problems, but can tell you that the answers to all your thyroid questions, including those you didn't know to ask, are at

There is another interaction between thryoid and ovarian hormones once they are in our systems that becomes important in the balancing process, but we're going to deal with that in a separate entry.

Nutrients necessary for the full metabolism of HRTs

One other interaction is of vital nutritional importance to users of HRT, and that is the effect estrogen has on your need for certain vitamins and minerals. While we often think of "interactions" as implying a negative relationship, there are many things necessary to fully and properly utilize our HRTs. In the case of these nutrients, then, it's a situation where the lack of them impairs our HRT effectiveness. Estrogen depletes zinc, magnesium and vitamin B6 from your system and yet requires them for proper metabolization. This may not sound like any big deal, but a large number of the complaints women attribute to HRT are in fact due to depletion of these three nutrients. Take a look at what they do.

Magnesium is a cofactor in over 300 enzymatic reactions in the body. It is necessary for the transmission of nerve impulses, muscular activity, temperature regulation, detoxification reactions, and for the formation of healthy bones and teeth. It also plays critical roles in energy production and the synthesis of DNA and RNA. Magnesium is a nutritional superstar when it comes to cardiovascular disease. Magnesium deficiency is associated with increased incidence of atherosclerosis, hypertension, strokes, and heart attacks. Low levels of magnesium can cause stiffness in blood vessels, which elevates blood pressure, and a contraction or spasm in the heart muscle, which can result in sudden death. Magnesium may be more important than calcium for bone health. It is involved in calcium metabolism, the synthesis of vitamin D, and the integrity of skeletal bone-crystal formation. Consuming adequate magnesium may reduce the risk of developing asthma and it is frequently useful as part of an overall treatment program. Magnesium helps to bind calcium to tooth enamel, thus creating an effective barrier to tooth decay. Current thinking is that you need to consume magnesium in a 1:2 ratio to calcium. That means that if your calcium RDA is 1200-1500 mg, you need 600-750 mg of magnesium taken along with it (as in, at the same time). Many foods contain good quantities of magnesium, so you may not need to obtain all of that total from supplements.

The symptoms of zinc deficiency include acne; impaired sense of smell and taste; delayed wound healing; anorexia; decreased immunity; frequent infections; depression; photophobia; night blindness; problems with skin, hair, and nails; menstrual problems; joint pain; and involuntary cyclical movements of the eyeball (nystagmus). Doses of up to 45 mg/day are considered by some sources to be safe, but regular intakes greater than 150 mg/day could be problematic; the link contains recommended levels.

Deficiencies of vitamin B6 manifest primarily as dermatologic, circulatory and neurologic changes. Because of its many metabolic roles, there are a wide variety of deficiency symptoms, which include the following: depression, sleep disturbances, nerve inflammation, PMS, lethargy, decreased alertness, anemia, altered mobility, elevated homocysteine (one of the most critical independent risk factors to cardiovascular disease), nausea, vomiting, seborrheic dermatitis. The RDA for vitamin B6 is 1.5-2 mg/day and amounts over 50 mg/day are considered toxic.

While we have important needs for all of these nutrients, we need to remember that with this kind of supplementation, as with HRT, more than needed is not just not as good, it is actively harmful. So while many of us may choose to supplement some or all of them, it's important to also count into those totals the amounts we get from our diets.