Testosterone Levels Don't Drop Sharply in Menopause

Correcting testosterone misinformation. Again.

I’m always amazed that when I correct misinformation about testosterone online it causes such a kerfuffle. The things I get nasty messages about…really, that could be its own post one day.

The most recent testosterone dust up started after this article was published. The article is well-sourced and accurate.

It discusses some very real concerns about over prescribing. As I entered into some discussion about the article, I saw defenders make some interesting claims, and two caught my eye. One, that testosterone levels are three times higher than estrogen before menopause and the other, testosterone levels drop sharply with menopause. These statements were offered as evidence the article was incorrect.

I’m not sure where these two claims originated, but the first one is medically nonsensical and the second one is incorrect. Like really incorrect. Let’s take a closer look. 

Are Testosterone Levels Three Times Higher than Estradiol Before Menopause?

Total testosterone is indeed about three times higher than estradiol before menopause (specifically at the start of each menstrual cycle), but so what? It’s a good medical trivia question, but meaningless. The implication, I suppose, is that if testosterone levels are higher than estradiol it must be an even more important hormone, ergo doctors are being neglectful when they fail to prescribe it. Except levels of a hormone don’t tell us if a hormone is important or not, because it’s not a competition. Testosterone levels could be 1,000 times higher than estradiol before menopause and that still would’t be a reason to prescribe it, because we don’t prescribe any hormone in menopause based on levels being low. We treat patients based on symptoms. Anything else is not standard of care. 

Also, total testosterone doesn’t tell us the whole picture. The effect of a hormone also depends on receptors. And most testosterone is bound to a carrier protein called SHBG (sex hormone binding globulin); only the unbound testosterone is free to act on tissues, and unbound testosterone is actually much lower than estradiol. I could say, “Testosterone is unimportant because unbound levels are much lower than estradiol before menopause.” Except, I know the medicine, so I don’t.

Do Testosterone Levels Drop Sharply in Menopause?

Nope. 

I think this is a good one to look at more closely, because I can understand how that could lead someone to believe that testosterone therapy is warranted. After all, a drop in estrogen is associated with symptoms for many, so it is logical to assume the same would also be true for testosterone. Additionally, dropping sharply sounds like something drastic has happened to you and needs treatment.

Let’s take a closer look. 

Testosterone comes from three sources:

• The ovaries makes about 25%

• The adrenal glands make about 25%

• And other tissues convert a hormone called androstenedione into testosterone (about 50%). Androstenedione production is split about 50/50 between the ovary and adrenal gland.

And yet testosterone levels don't drop sharply at menopause, levels gradually decline during the ovulatory years, and remain relatively stable right before and after menopause. In fact, levels increase a little in the 70s. 

How is this possible? Doesn’t the ovary stop functioning with menopause? Well, follicles (eggs) stop developing, but the ovarian stroma (the supporting tissue around the follicles) continues to produce testosterone. This happens because hormones from the pituitary stimulate the stroma to produce androstenedione, which is converted into testosterone.  

In one study, researchers measured hormone levels from over 1,400 women, from ages 18 to 75. The deepest drop in testosterone (not a sharp cliff) was in the early reproductive years and no menopause-related decrease was seen. Basically, there is a gradual age-related decline which is greater before age 25 and levels off before menopause.

Another excellent paper followed hundreds of women over seven years, before and after their final menstrual periods (FMP), and concluded there was no change in testosterone related to the final menstrual period. Testosterone levels were stable for several years before and after menopause.

The fact that testosterone levels don’t drop with menopause, but rather the decline is gradual and age-related isn’t recent knowledge and it’s pretty basic menopause physiology. 

The Only Indication for Testosterone is Low Libido

Testosterone therapy in menopause is only recommended for decreased libido after non medication options have been tried and failed. It’s important to point out that some of the non medical therapies, like mindfulness, have far better studies supporting their effectiveness. The effect of testosterone for libido is moderate at best, resulting in 1-2 extra episodes of sex in 4 weeks. And it’s important to know that these studies are generally with women already having sex with some regularity, so how this works for people who have sex very infrequently isn’t known. But the data supports giving testosterone a try for libido concerns, and if no improvement in by 6 months, then stopping it. 

But what about other indications?

Testosterone has been looked at for hot flashes, cognition, mood and bone health. One meta-analysis looked at 54 studies (in 2005) and another at 35 studies (in 2014) and both concluded there were no beneficial effects. The International Menopause Society also published a review of the literature in 2019, and reached the same conclusions. Now it’s true that not all of the studies were designed to look at testosterone in a way that could best answer these questions. Could additional studies reveal something different? Absolutely, that’s science. We could also get data next week that tells us something we don’t know about estrogen therapy in menopause. But future data that doesn’t exist is not a basis for prescribing. We have to use the available data and not just wing it. Also, the data is pretty good here. In fact, it’s good enough data that the following expert societies and guidelines only recommend testosterone for low libido and not for any other reason:

• North American Menopause Society

• British Menopause Society

• NICE Guidelines

• Royal College of Obstetricians and Gynecologists

• Australasian Menopause Society

• The Endocrine Society

• International Menopause Society

If the conclusions were wishy-washy we just wouldn’t see this consensus. 

And in addition to all the studies included in the these meta-analyses, we have a year-long prospective trial of women with primary ovarian insufficiency, which mean those who stopped ovulating before age 40. The trial found that adding testosterone provided no benefit over estrogen for any metric. 

It seems that testosterone prescriptions for reasons other than libido are largely driven by private practices that operate outside of insurance and the public health care system (in the US, Canada, and the UK, anyway). I am always suspicious when doctors who charge cash have different conclusions than all the experts. Prescribing testosterone is profitable. It is the one hormone where you do need to monitor levels, so it creates repeat customers and private practitioners charge to review the lab work. The idea that doctors who directly profit from prescribing testosterone know more about it than all the experts who disclosed their biases to write the many guidelines is, in my opinion, laughable. I mean, okay, go ahead and publish your meta-analysis in a reputable journal if the data is so clear to you?

The other thing that testosterone offers private practices is the illusion that they have something better. If you are going to charge luxury prices, you need a special product.

The Role of Testosterone is Complicated

When it comes to sexual function, we know that for women libido is unrelated to testosterone levels, but sometimes giving women in menopause a low dose of testosterone helps. 

To my knowledge, none of the doctors who prescribe testosterone outside of these indications have ever provided any solid data to back up their recommendations. I’ve looked at several of their websites. I just read things along the lines of “Some patients feel better…” That is anecdote, and when we have data we don’t use anecdote. Or rather, we shouldn’t. Otherwise, we’d be okay saying homeopathy works because some people say so, when the reality is we have a myriad of studies that say homeopathy doesn’t work (and we know it’s biologically implausible). 

I know there are people who say testosterone has helped them, but the studies we have say that an equal number of women who received a placebo felt the same way. I dislike anecdotes, but I will say for every person leaving a comment on my Instagram that testosterone helped them, I get two or three saying the opposite. I see complications from testosterone over prescribing, as well as people who have been on it for years and it clearly hasn’t had the impact they wanted. Meaning, no one stopped their six month trial when it didn’t work.

The idea that women in menopause should have FOMO (Fear of Missing Out) with testosterone is not supported by the literature. Look, I’m in menopause. My mother died from osteoporosis and sarcopenia (wasting of muscles). If I thought low dose testosterone was going to provide extra protection for my bones and muscles over estrogen (estrogen is just for my bones, BTW), I’d be on it pronto. I’m not. What I am doing is weight lifting and walking 6,000 steps a day and cutting back on alcohol because these are the actions that science tells us really works for muscles, bones, and the brain. 

References

1. Somboonporn W, Davis S, Seif MW, Beel R. Testosterone for peri- and postmenopausal women. Cochrane Database Syst Rev 2005;CD004509.

2. Elraiyah T, Sonbol MB, Wang Z, et al. Clinical review: The benefits and harms of systemic testosterone therapy in postmenopausal women with normal adrenal function: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2014;99:3543.

3. Davis SR, Barber R, Panay N, et al. Global Consensus Position Statement on the Use of Testosterone Therapy for WOmen. J. Clin Endocrinol Metab 2019;104:4660.

4. Burger HG, Dudley EC, Cui J et al. A Prospective Longitudinal Study of Serum Testosterone, Dehydroepiandrosterone Sulfate, and Sex Hormone-Binding Globulin Levels through the Menopause Transition. J Clin Endocrinol Metab, 2000;85:2832.

5. Davidson SL, Bell R, DOnath S, et al. Androgen Levels in Adult Females: Changes with Age, Menopause, and Oophorectomy. J Clin Endocrinol Metab:2005;90:3847. 

6. Struass JF, Barbieri RL, Gargiulo AR. Yen & Jaffe’s Reproductive Endocrinology, 8th Edition.