I’m often sent screenshots from various sites about menopausal hormone therapy (MHT), and lately it’s been a lot about cognition and also about testosterone. Sometimes about one or the other, and sometimes about testosterone for cognition. I suspect some of this is due in part to an ever growing number of practitioners making bold claims about the supposed benefits of testosterone. I’ve even seen comments along the lines of, “It’s replacing a hormone women are missing because of menopause.”

So what’s up with these claims? Can MHT lift brain fog and is testosterone an essential part of MHT?.

Let’s start with some basics. Menopausal Hormone Therapy

Menopausal hormone therapy, or MHT, is also known by its older name of hormone replacement therapy (HRT), but that latter term is misogynistic and medically incorrect. Replacement implies there is a deficit, meaning the ovaries should be making estrogen, but are not. That cannot apply to menopause as menopausal ovaries are not supposed to make estrogen. HRT implies that menopause, a normal phase of life, is a disease, and it is not. MHT is a more precise term as what is being prescribed are hormones for treatment of menopause.

Standard MHT is estrogen. The most studied and safest is estradiol given across the skin (also called transdermal therapy). Estradiol is the main estrogen and is made primarily by the ovaries before menopause, but also in smaller amounts in various tissues both before and after menopause. After menopause the estradiol produced in these other tissues doesn’t change.

Women with a uterus also need another hormone called a progestogen, either progesterone or a synthetic version called a progestin. This is because estrogen alone will cause uncontrolled growth of the lining of the uterus (endometrium), which can lead to cancer. The progestogen protects against this.

In this post when I mention MHT I mean using the hormones in such a way that they enter the bloodstream. This is known as systemic therapy. Local therapy applies to giving estrogen vaginally to treat vaginal and vulvar changes associated with menopause and the hormone does not enter the bloodstream.

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Cognitive Changes and Menopause

These changes do exist and are often known as brain fog. When we say cognitive changes, we mean difficulty concentrating and remembering things. Brain fog impacts about two-thirds of women during their menopause transition (perimenopause) or early menopause (the first year or two after the last menstrual period).

While brain fog is understandably worrying to many women, it is not medically concerning. It is not a sign of early onset dementia and we have excellent data to show this is a temporary phenomenon. Some women may be reassured to know that women who do have these temporary cognitive changes still perform as well as men or even better on memory testing.

Interestingly, hot flushes/flashes, depression, anxiety, and sleep disturbances are not linked with these cognitive changes. Meaning we don’t think that they are due to depression or waking up at night from hot flushes. This is from a large prospective study that followed women through their menopause transition and beyond (the SWAN study or the Study of Women’s Health Across the Nation).

The exact cause of brain fog is unknown. One possibility is the brain remodeling that happens with menopause, shown in very elegant studies by Dr. Lisa Mosconi and her group. In menopause, some areas of the brain get smaller, but others grow to compensate. We had a great discussion about it on Instagram. Many reproductive functions depend on signaling from the brain and after menopause this signaling is no longer needed. It is possible that these areas that shrink may reflect pruning of some of these now unnecessary pathways.

Think of menopause as a new update for your operating system. Just like when your phone updates things are glitchy for a while, but then your apps catch up and you get used to the new interface. Everything settles and what was once new is now normal and no longer disruptive. This is what is happening with menopause.

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Menopausal Hormone Therapy and Cognition

MHT is not indicated for cognitive changes. We know this because of some excellent studies, including the following:

The KEEPS trial, which evaluated the cognitive impact of MHT after 48 months. No impact on cognition, negative or positive.

The ELITE trial, which evaluated the cognitive impact of MHT after 2.5 years and 5 years. No impact on cognition, negative or positive.
The WHIMSY trial, no impact of MHT on cognition at 7.2 years.

And this makes sense, because cognitive changes are temporary. Also, brain fog were caused by low levels of estrogen and hence treatable with estrogen, they wouldn’t be temporary.

Women with cognitive changes need an evaluation to make sure these changes are not a symptom of something else, such as severe depression, a thyroid disorder, or sleep apnea. And they need reassurance and support.

Why Do We Prescribe MHT?

Well, not for cognition! Studies are pretty clear that it does not help. We do prescribe MHT for hot flushes (flashes), sleep disturbance due to hot flushes (flashes), low mood in the early menopause transition (not moderate or severe depression), and for prevention of osteoporosis. We don’t have data to tell us if treating hot flushes or sleep disturbances with estrogen helps with cognitive changes. It is possible that improving sleep with MHT (or other therapies) may make the cognitive changes less disruptive. It is true that most of us handle things better when we have enough sleep, but it is important to be clear that we don’t have data here.

The North American Menopause Society has new guidelines on osteoporosis, so I will get a post up about those in a week or so. We typically don’t give MHT for vaginal changes (genitourinary syndrome of menopause) as it may not be enough. If vaginal issues are the only concern, we treat patients with estrogen or another hormone called DHEA given vaginally. If someone has vaginal symptoms and is starting MHT it may be reasonable to wait three months to see if the estrogen in the MHT helps before immediately starting vaginal therapy.

Where Does Testosterone Fit in for MHT?

It is not recommended for hot flushes, mood, sleep, osteoporosis, or cognition. So it doesn’t fit in for MHT.

And no, this is not just my opinion, this is the opinion of ALL the major menopause and endocrinology societies.

You can find the full statement on testosterone and menopause here, but the most pertinent part for MHT is as follows:

Recommendations regarding the effects of testosterone on wellbeing, mood and cognition in postmenopausal women

There is insufficient evidence to support the use of testosterone to enhance cognitive performance, or to delay cognitive decline, in postmenopausal women (Insufficient).
Available data show no effect of testosterone therapy on general wellbeing (Level I, Grade A).
Testosterone may improve wellbeing in premenopausal women but data are inconclusive (Level 1, Grade B).
Available data do not show an effect of testosterone on depressed mood (Level I, Grade B).

Testosterone is part of the algorithm for low libido. This is not MHT, this is treatment of libido. And it is certainly not the first line therapy. The role of testosterone here is complex, so I recommend that anyone who wants to know more about this to head to the chapter on libido in my book the Menopause Manifesto.

This is also the opinion on UpToDate, which is an excellent resource for medical professionals to stay, well, up to date...on everything. And also the recommendations from the NICE guidelines (you can read those here).

It is important to remember that testosterone levels do not drop dramatically with menopause because the bulk of the testosterone is produced in the adrenal glands and the stroma of the ovary (this is the tissue of the ovary that surrounds the eggs). Most of the decline in testosterone levels are related to aging.

So Why Do Some Providers Recommend MHT for Cognition or Recommend Testosterone as a Regular Part of MHT?

You will have to ask them!

It is clear that testosterone pellets are a money maker, both from the insertion and interpreting all the blood work that is required as part of the therapy. As an aside, testosterone pellets are dangerous and every medical society recommends against them. You can read more about why they are so bad in this post).

I wonder if there is profit in implying that testosterone is part of MHT? When MHT doesn’t help a woman for cognition (and as we’ve discussed it won’t) or treat every symptom of menopause (not unexpected), women may look elsewhere because they’ve been led to believe that hormones will help everything, so maybe they are just not on the right hormones? Doctors that offer testosterone as part of MHT can offer “something else those other doctors won’t give you.” Basically, the illusion they have special care or knowledge or both. In addition, testosterone therapy requires following regular blood levels, so this keeps people coming back for required appointments and regular blood work they have to pay for and pay their doctor to interpret. All that testing and the exclusivity angle may augment the placebo effect. There is data to tell us that the more a therapy costs, the greater the placebo effect.

Summary

This is a lot of information, so let’s summarize.

MHT is not useful for the temporary cognitive changes associated with the menopause transition and early menopause.

Cognitive changes are temporary and many women even report a clarity once they are through the menopause transition. Maybe clearing out those old, unused pathways liberates the brain? After all, there is so much data to tell us that historically women in menopause have been an essential part of society.

MHT is effective therapy for hot flushes or flashes, sleep issues related to hot flushes, mild mood changes (not severe depression), and prevention of osteoporosis.

Testosterone is only recommended for libido issues, but that is not part of MHT, it is for treatment of libido.

Testosterone is not recommended for hot flushes, depression, mood changes, osteoporosis, or cognitive changes. This is the opinion of all of the major menopause societies.

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References:

Global Consensus Position Statement on the Use of Testosterone Therapy for Women, International Menopause Society et al https://www.imsociety.org/statements/position-papers-and-consensus-statements/

NICE Guidelines https://www.nice.org.uk/guidance/ng23/chapter/recommendations

Gleason CE, Dowling NM, Whartone W, et. al. Effects of Hormone Therapy on Cognition and Mood in Recently Postmenopausal Women: Findings from the Randomized, Controlled KEEPS-Cognitive and Affective Study. PLoS Med;2015 Jun 2;12(6):e1001833

Henderson St. John JA, Hodis HN, et. al. Cognitive effects of estradiol after

Menopause. A randomized trial of the timing hypothesis. Neurology 2016.

Espeland MA, Shumaker SA, Leng I, et. al.Long-Term Effects on Cognitive Function of Postmenopausal Hormone Therapy Prescribed to Women Aged 50 to 55 Years. JAMA Intern Med. 2013;173.

Greendale GA, Karlamangla AS, Maki PM. The Menopause Transition and Cognition. JAMA March 12, 2020.

Greendale GA, RG, Wight, Huang M-H, et al. Menopause-associated Symptoms and Cognitive Performance: Results From the Study of Women’s Health Across the Nation. Am J Epidemiol;171, 2010.

Mosconi L, Berti V, Dyke J, et. al. Menopause impacts human brain structure, connectivity, energy metabolism, and amyloid-beta deposition. Nature. June 2021.

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