HRT: A Tale Of Two Approaches

In yesterday’s newsletter, we asked you for your assessment of menopausal hormone replacement therapy (HRT).

• A little over a third said “It can be medically beneficial, but has some minor drawbacks”
• A little under a third said “It helps, but at the cost of increased cancer risk; not worth it”
• Almost as many said “It’s a wondrous cure-all that makes you happier, healthier, and smell nice too”
• Four said “It is a dangerous scam and a sham; “au naturel” is the way to go”

So what does the science say?

Which HRT?

One subscriber who voted for “It’s a wondrous cure-all that makes you healthier, happier, and smell nice too” wrote to add:

❝My answer is based on biodentical hormone replacement therapy. Your survey did not specify.❞

And that’s an important distinction! We did indeed mean bioidentical HRT, because, being completely honest here, this European writer had no idea that Premarin etc were still in such wide circulation in the US.

So to quickly clear up any confusion:

• Bioidentical hormones: these are (as the name suggests) identical on a molecular level to the kind produced by humans.
• Conjugated Equine Estrogens: such as Premarin, come from animals. Indeed, the name “Premarin” comes from “pregnant mare urine”, the substance used to make it.

There are also hormone analogs, such as medroxyprogesterone acetate, which is a progestin and not the same thing as progesterone. Hormone analogs such as the aforementioned MPA are again, a predominantly-American thing—though they did test it first in third-world countries, after testing it on animals and finding it gave them various kinds of cancer (breast, cervical, ovarian, uterine).

A quick jumping-off point if you’re interested in that:

Depot medroxyprogesterone acetate and the risk of breast and gynecologic cancer

👆 this is about its use as a contraceptive (so, much lower doses needed), but it is the same thing sometimes given in the US as part of menopausal HRT. You will note that the date on that research is 1996; DMPA is not exactly cutting-edge and was first widely used in the 1950s.

Similarly, CEEs (like Premarin) have been used since the 1930s, while estradiol (bioidentical estrogen) has been in use since the 1970s.

In short: we recommend being wary of those older kinds and mostly won’t be talking about them here.

Bioidentical hormones are safer: True or False?

True! This is an open-and-shut case:

❝Physiological data and clinical outcomes demonstrate that bioidentical hormones are associated with lower risks, including the risk of breast cancer and cardiovascular disease, and are more efficacious than their synthetic and animal-derived counterparts.

Until evidence is found to the contrary, bioidentical hormones remain the preferred method of HRT. ❞

Further research since that review has further backed up its findings.

Source: Are Bioidentical Hormones Safer or More Efficacious than Other Commonly Used Versions in HRT?

So simply, if you’re going on HRT (estrogen and/or progesterone), you might want to check it’s the bioidentical kind.

HRT can increase the risk of breast cancer: True or False?

Contingently True, but for most people, there is no significant increase in risk.

First: again, we’re talking bioidentical hormones, and in this case, estradiol. Older animal-derived attempts had much higher risks with much lesser efficaciousness.

There have been so many studies on this (alas, none that have been publicised enough to undo the bad PR in the wake of old-fashioned HRT from before the 70s), but here’s a systematic review that highlights some very important things:

❝Estradiol-only therapy carries no risk for breast cancer, while the breast cancer risk varies according to the type of progestogen.

Estradiol therapy combined with medroxyprogesterone, norethisterone and levonorgestrel related to an increased risk of breast cancer, estradiol therapy combined with dydrogesterone and progesterone carries no risk❞

In fewer words:

• Estradiol by itself: no increased risk of breast cancer
• Estradiol with MDPA or other progestogens that aren’t really progesterone: increased risk of breast cancer
• Estradiol with actual progesterone: back to no increased risk of breast cancer

Source: Estradiol therapy and breast cancer risk in perimenopausal and postmenopausal women: a systematic review and meta-analysis

So again, you might want to make sure you are getting actual bioidentical hormones, and not something else!

However! If you are aware that you already have an increased risk of breast cancer (e.g. family history, you’ve had it before, you know you have certain genes for it, etc), then you should certainly discuss that with your doctor, because your personal circumstances may be different:

❝Tailored HRT may be used without strong evidence of a deleterious effect after ovarian cancer, endometrial cancer, most other gynecological cancers, bowel cancer, melanoma, a family history of breast cancer, benign breast disease, in carriers of BRACA mutations, after breast cancer if adjuvant therapy is not being used, past thromboembolism, varicose veins, fibroids and past endometriosis.

Relative contraindications are existing cardiovascular and cerebrovascular disease and breast cancer being treated with adjuvant therapies❞

Source: HRT in difficult circumstances: are there any absolute contraindications?

HRT makes you happier, healthier, and smell nice too: True or False?

Contingently True, assuming you do want its effects, which generally means the restoration of much of the youthful vitality you enjoyed pre-menopause.

The “and smell nice too” was partly rhetorical, but also partly literal: our scent is largely informed by our hormones, and higher estrogen results in a sweeter scent; lower estrogen results in a more bitter scent. Not generally considered an important health matter, but it’s a thing, so hey.

More often, people take menopausal HRT for more energy, stronger bones (reduced osteoporosis risk), healthier heart (reduced CVD risk), improved sexual health, better mood, healthier skin and hair, and general avoidance of menopause symptoms:

Read more: Skin, hair and beyond: the impact of menopause

We’d need another whole main feature to discuss all the benefits properly; today we’re just mythbusting.

HRT does have some drawbacks: True or False?

True, and/but how serious they are (beyond the aforementioned consideration in the case of an already-increased risk of breast cancer) is a matter of opinion.

For example, it is common to get a reprise of monthly cramps and/or mood swings, depending on how one is taking the HRT and other factors (e.g. your own personal physiology and genetic predispositions). For most people, these will even out over time.

It’s also even common to get a reprise of (much slighter than before) monthly bleeding, unless you have for example had a hysterectomy (no uterus = no bleeding). Again, this will usually settle down in a matter of months.

If you experience anything more alarming than that, then indeed check with your doctor.

HRT is a dangerous scam and sham: True or False?

False, simply. As described above, for most people they’re quite safe. Again, talking bioidentical hormones.

The other kind are in the most neutral sense a sham (i.e. they are literally sham hormones), though they’re not without their merits and for many people they may be better than nothing.

As for being a scam, biodentical hormones are widely prescribed in the many countries that have universal healthcare and/or a single-payer healthcare system, where there would be no profit motive (and considerable cost) in doing so.

They’re prescribed because they are effective and thus reduce healthcare spending in other areas (such as treating osteoporosis or CVD after the fact) and improve Health Related Quality of Life, and by extension, health-adjusted life-years, which is one of the top-used metrics for such systems.

See for example:

Menopausal Hormone Replacement Therapy and Reduction of All-Cause Mortality and Cardiovascular Disease

Our apologies, gentlemen

We wanted to also talk about testosterone therapy for the andropause, but we’ve run out of room today (because of covering the important distinction of bioidentical vs old-fashioned HRT)!

To make it up to you, we’ll do a full main feature on it (it’s an interesting topic) in the near future, so watch this space 😎

Ladies, we’ll also at some point cover the pros and cons of different means of administration, e.g. pills, transdermal gel, injections, patches, pessaries, etc—which often have big differences.

That’ll be in a while though, because we try to vary our topics, so we can’t talk about menopausal HRT all the time, fascinating and important a topic it is.

Meanwhile… take care, all!