Hormones and rabbit holes

Medicine is confusing right now. Ok, it is always confusing because we try to base it on science and science is always changing. There are always special areas that are currently a mess. Hormones!

I speak to a patient recently who is female, premenopausal, and is getting hormone replacement therapy for hot flushes and not sleeping well from an outside source. The person wants me to order hormone tests. I do order hormone tests but not the ones she has in mind. I test a TSH, thyroid stimulating hormone, to see if she is low or high in thyroid.

She is thinking of me testing estrogen and progesterone and other related hormone levels. The party line from gynecology MDs and DOs is that these are not useful tests because women’s hormone levels are so varible. However, there are lots of naturopaths out there and functional medicine MDs and DOs who will test levels. Why is the patient asking ME to test them? Most of those naturopaths and functional medicine providers do not take insurance and charge cash. Also, insurance may not pay for them anyhow because the party line is that they aren’t useful. Why would the cash providers check levels? One reason is CASH. Another is to prescribe “bioequivalent hormone replacement”. Sounds natural, right? Well, the natural thing was for the hormones to stop at menopause and all of the hormones are either made in a laboratory from plant pre-estrogens or from pregnant mare urine, so bioequivalent seems to imply natural but it really isn’t. Pills do not grow on trees, they are made by humans in laboratories.

However, I question party lines, and off I go down the hormone rabbit hole. The current guidelines are that female hormone replacement, after menopause, should be lowest dose possible and only for a maximum of three years because of the increased risk of breast cancer. This doesn’t address my question: does premenopausal hormone replacement count as part of those three years? I may need to ask gynecology. I don’t think it counts. A woman is postmenopausal when she has had no periods for a year. Or had her ovaries removed. Or if she’s had a hysterectomy and still has her ovaries, a yearly follicle stimulating hormone and lutienizing hormone test. Both tests rise when the ovaries stop making hormones and eggs.

Also, there is another caveat. We know that when men are on opioids, the opioids can suppress their hormones and lower testosterone. Here is a paper: https://pubmed.ncbi.nlm.nih.gov/31511863/. Half the men studied in multiple studies had low testosterone when on chronic opioid therapy. 18429 subjects (patients) in 52 studies. That is a lot. Women studied? NONE. What? Yeah, none. Why? Here is part of the answer: about a decade ago I worked with the UW Telepain group and asked the head of the UW Pain clinic a question. “If opioids lower hormones in men, do they in women too?”

His reply, “I don’t know.”

“Have you ever tested a woman?”

“No.”

“Isn’t that sort of sexist?”

“Yes.”

So here I am, rechecking a decade later, and we still don’t know if giving women chronic opioids messes up their hormone levels. It would be more complicated and difficult to check women. We might have to do individual hormone baselines or something in premenopausal ones, say, 2 weeks after menses. Remember that for most of the history of medicine, clinical drug trials were only done in men, because, well, sexism. They said women could get pregnant. Yes, but then we gave the drugs to women who could get pregnant. Also, postmenopausal women can’t get pregnant. The whole thing seems stupid to me.

There is an interesting new finding here: https://neurosciencenews.com/estrogen-t-cells-pain-28548/ . Apparently in women, estrogen and progesterone work on receptors at the base of the spine to reduce pain signals using T cells, part of the immune system. The article says this doesn’t happen in men, but they were studying mice. The male mice didn’t seem to have worse pain after estrogen and progesterone were blocked. The female mice were in more pain. But wait, estrogen and progesterone are produced in men as a by product of making testosterone. Less than women, until menopause. Then the 70 year old man has more estrogen and progesterone than his postmenopausal wife. The article says that they don’t know why the receptors are in women and female mice (um, my intuitive guess would be childbirth and micebirth, right? Men don’t do that and women giving birth to a child after the first one sometimes say, “WHY did I want to do THIS again?” I think those receptors are so that women and mice can get through more than one pregnancy.) Now I need to read the article again because maybe men and male mice don’t have the receptors, even though they do have some estrogen and progesterone. Maybe they just don’t have enough estrogen and progesterone.

Maybe we can’t figure out women’s hormone because men aren’t smart enough, heh, heh. Yes, that is sexist right back at all those historical figures who didn’t study women.

At any rate, that still doesn’t answer my two questions: does premenopausal hormone replacement count towards the three year total beyond which hormone replacement increases the risk of breast cancer? And does chronic opioid treatment lower women’s hormone levels?

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For the Ragtag Daily Prompt: hormone.

I took the photograph of a Port Townsend rabbit in 2011.