Adding Testosterone to HRT for Women
At-a-Glance:
- Low estrogen during perimenopause is what causes hot flashes, vaginal dryness, brain fog, bone loss, and other symptoms
- Unfortunately, the important role testosterone plays is almost always overlooked.
- Testosterone replacement in women can improve cognition, mood, and libido.
By Dr. John Neustadt
The goal of hormone replacement therapy (HRT) is to bring hormone levels back to their healthy, normal range. Because decreasing hormones during menopause can cause hot flashes, joint pain, vaginal dryness, and other symptoms, HRT is often considered during this time. Less frequently discussed, but also important, is testosterone.
Estrogen and testosterone are made from cholesterol. Most of the time, ‘estrogen’ is written in the singular; however, it is more accurately referred to as ‘estrogens’. That’s because there are multiple types of estrogens. They are produced by different tissues and at various times during a woman’s life.
Estradiol (E2) is the principal sex hormone circulating during a woman’s reproductive years, is the most potent estrogen, and is approved by the FDA for maintaining bone density.1 E2 is synthesized in the ovaries from puberty to menopause. It is responsible for breast development, widening of the hips, and the growth of pubic and underarm hair. The decrease in E2 during menopause is what is responsible for hot flashes, vaginal dryness, brain fog, bone loss, and other symptoms.
During a woman’s normal menstrual cycle, E2 stimulates the thickening of the endometrial lining. Progesterone counteracts this process by preventing the uterine lining from becoming too thick. This is one reason why low-dose progesterone is often combined with E2 during HRT. Progesterone also has bone-building effects, and the combination has been shown to reduce fractures in postmenopausal women with osteoporosis.2
E2 and Bone Health
E2 is crucial for maintaining bone health. The fastest bone loss occurs when E2 levels decrease during menopause and for the ten years after.3 While it is only one of many hormones affecting bone health, E2 helps bones by activating genes that increase bone formation and collagen production, decrease bone loss, and reduce inflammation.4
E2 also increases bone mineral density (BMD) and maintains bone strength. Women in the National Osteoporosis Risk Assessment (NORA) study taking hormone replacement therapy had a 40% lower risk of hip fractures compared to women who had never used hormone replacement therapy.5
In a meta-analysis of 28 studies involving 33,426 women, the use of menopausal hormone replacement therapy was associated with a 26% reduction in overall fracture risk, a 28% lower risk of hip fractures, and a 37% lower risk of vertebral fractures. Importantly, in their analysis, the researchers determined that the bone-protective effects of hormone replacement may decrease after a person stops taking it or when it is started after the age of 60.6
Optimal E2 Level
If beginning HRT, testing hormone levels before and during treatment is important to ensure you’re within the optimal range. The optimal E2 plasma concentration for relieving menopausal symptoms and preventing bone loss is 60-150 pg/mL (550 pmol/L).7 At the lower end of that range (60 pg/mL), hot flashes are reduced by 50%, and bone loss is prevented.
But research indicates that women experience even greater benefits at higher E2 levels. At 100 pg/mL (400 pmol/L), hot flashes are eliminated, and new, healthy bone is created.8,9
Adding Testosterone
What is rarely considered in discussions of HRT is the vital role testosterone plays in women’s health. A common complaint from women going through perimenopause is feeling as though they have lost themselves. One woman told me, “I don’t even know who I am anymore.” The body that they depended on their entire lives no longer functions the same. One of the most distressing effects is the loss of sexual desire. Not only can they feel terrible about it for what they’ve lost, but it can also strain their relationships with their partners, leading to feelings of guilt. While estrogen replacement therapy can improve vaginal dryness and pain during intercourse, it has only a small or no effect on overall sexual health.10
Like testosterone in men, in women, testosterone levels decrease with age and are up to 50% lower in menopausal women compared to women in their 20s.11 Despite that, the important role testosterone plays in women’s health is almost always completely overlooked. Not only does testosterone boost cognition and mood, it influences sexual motivation in women, including feeling interested in sex, initiating sex, and responding to sexual stimuli.
Ordering a testosterone test can tell you if you don’t have enough. If your testosterone is toward the lower end of normal, or if you have testosterone deficiency, along with symptoms of low testosterone, testosterone replacement therapy (TRT) is an important option to consider. While not approved by the FDA for menopausal symptoms, an increasing number of healthcare providers are recognizing its importance and prescribing it off-label.
The 2019 Global Consensus Position Statement on the Use of Testosterone Therapy in Women, authored by researchers from nearly a dozen medical societies worldwide, recommends TRT in women with low sexual function. Specifically, TRT in doses that maintain testosterone within a healthy physiological range enhances “sexual desire, arousal, orgasmic function, pleasure, and sexual responsiveness,” while reducing sexual distress.12
TRT in women has also been shown to improve cognition, mood, and libido. In a clinical trial involving 510 perimenopausal and postmenopausal women experiencing persistent low libido, cognitive difficulties, and depression, four months of transdermal testosterone enhanced these areas. Cognition improved in 39% of women, mood in 47%, and libido in 52%. According to the authors, “The finding that mood and libido improved to a similar degree is not surprising given that libido is a mood.” Importantly, before the study, all these women had already been on HRT (estrogen with or without progesterone) for at least three months. Yet, they still struggled with decreased cognition, mood, and low libido.13
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References
1 Rettberg JR, Yao J, Brinton RD. 2014;35(1):8–30.
2 Prior JC. 2018/07/04 2018;21(4):366–374.
3 Sunyer T, Lewis J, Collin-Osdoby P, et al. 15, 1999 1999;103(10):1409–1418.
4 Stepan JJ, Hruskova H, Kverka M. 2019;17(6):465–473.
5 Barrett-Connor E, Wehren LE, Siris ES, et al. 2003;10(5):412–9.
6 Zhu L, Jiang X, Sun Y, Shu W. 2016;23(4):461–70.
7 de Lignieres B. 1996;23 Suppl:S31–6.
8 Armston A, Wood P. 2002;39(Pt 3):184–93.
9 Steingold KA, Laufer L, Chetkowski RJ, et al. 1985;61(4):627–32.
10 Meziou N, Scholfield C, Taylor CA, et al. 2023;30(6):659–671.
11 Rohr UD. 2002;41 Suppl 1:S25–46.
12 Davis SR, Baber R, Panay N, et al. 2019;104(10):4660–4666.
13 Glynne S, Kamal A, Kamel AM, et al. 2025;28(3):541–550.
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