HRT, And One More Way Motherhood Might Be Wrecking Your Life

A presentation last week at the 9th Annual Canadian Neuroscience Meeting brings some clarity (or complexity, depending on whether you’re a glass-half-full or glass-half-empty kind of critter) to the Good, the Bad, and the Completely Confusing topic of menopause-related hormone replacement therapy (HT). We say “completely confusing” because folks with ovaries have been subjected to a solid century of being jerked around on menopause-related HT recommendations depending on whether Something Really Great was discovered/invented or Something Really Bad was unearthed.

Before getting to the crux of the Canadian Neuroscience convention presentation, let us take you on a quick joy ride through 100+ years of the hormone replacement therapy roller-coaster (or just tl;dr straight to the money-shot):

The late 19th century brought the discovery that injection of extracts (comprised of both estrogen and progesterone) from ovarian tissue, placenta and urine from pregnant women were found to improve symptoms of menopause. That seems very fashion-forward for late 1800s medicine!¹
Then there was Emmenin (not to be confused with Eminem) in the 1930s, made from the urine of pregnant Canadians,² that was the first water-soluble estrogen able to serve as “a remedial agent for certain feminine disorders.”³ Now women could gulp their replacement estrogen in pill form instead of via shots-shots-shots-shots-shots!
Not to be overlooked is the successor to Emmenin: Premarin – that is, pregnant mare urine⁴ – that came galloping onto the scene in 1943.⁵ Larger volumes of estrogens were able to be extracted from pregnant equine urine than from pregnant human urine, presenting a more lucrative opportunity for production.⁶ (It bears mentioning that controversy has surrounded this means of estrogen acquisition ever since.)
Estrogen-only hormone replacement therapy as treatment for symptoms of menopause really took off in the 1960s and early 1970s until a study linking estrogen therapy and endometrial cancer crashed the party.⁷ Wait – so hormone replacement therapy is BAD? Check!
Use of HT in the 1980s and 90s increased once again as progestogen was added to the HT cocktail to mitigate estrogen’s overenthusiastic tendencies when left all alone.⁸ Ok, so HT is GOOD – got it!
Some studies were even showing that HT may have potential benefits of reducing risk of heart disease, dementia,⁹ and even osteoporosis.¹⁰ Ok for reals – HT is actually the best thing since toast! Hurray! HT for erryone!
Then along came results from the Women’s Health Initiative in 2010, showing that even HT with progestogen was linked to increased risks for heart attacks, strokes and blood clots.¹¹ Ok – we give up.

So back to the presentation from this week’s 9th Annual Canadian Neuroscience Meeting where Dr. Liisa Galea discussed her team’s research at the University of British Columbia. Dr. Galea’s team previously published research showing that pregnancy and motherhood causes “changes in the architecture of connections in the hippocampus,” a region of the brain involved in memory and spatial ability,¹² which is kind of a big deal all on its own. But in Dr. Galea’s most recent research, they investigated¹³ whether a) different forms of estrogen made any difference in cognition and neuroplasticity, and/or b) whether the variable forms of estrogen had different impacts based on whether pregnancy/motherhood had been experienced previously.

The results show that (drumroll, please!)

one form of estrogen – estradiol (found in greater amounts in younger women versus older women) was shown to have greater benefit on cognition and neuroplasticity.¹⁴
the other form of estrogen tested – estrone (found in greater amounts in older women versus young¹⁵ ) was shown to improve learning in rats that had never been pregnant, while it appeared to impair learning in age-similar rats that had given birth once.¹⁶

Got that? Not only does motherhood impact the physical architecture of the hippocampus, but some forms of HT may be less effective if you’ve been pregnant.

The implication for human use of HT as a means to treat neuro-degenerative disorders?¹⁷ Dr. Galea asserts that:

“Hormones have a profound impact on our mind. Pregnancy and motherhood are life-changing events resulting in marked alterations in the psychology and physiology of a woman. Our results argue that these factors should be taken into account when treating brain disorders in women”¹⁸

While this may not exactly simplify the overall cost/benefit-analysis of using HT, it suggests that factors like pregnancy history might be another consideration taken into account when running the calculus.¹⁹

And also, apparently brain modification is just one more way that motherhood is wrecking your life.