02/24/2025
From the desk of Dr DeSantis:
Recent study involving the effects of Testosterone Therapy on Mood and Cognitive Symptoms
Sarah Glenn and Luis Nusen et al published their results in the Archives of Women’s Mental Health (September 2024). They looked at perimenopausal and menopausal women on hormone therapy. This is important since International guidelines in the past have only reported on menopausal women. Testosterone levels do not drop to zero at menopause. This is a gradual process.
Overall they reported a 47% improvement in mood and 39% improvement in cognition. Libido was improved in 52% of women. Two-thirds of women transitioning into menopause report significant cognitive impairments. We talk about brain fog, however, women may describe their symptoms as fatigue, memory issues, difficulty concentrating, trouble verbalizing and decreased ability to multitask.
Major depressive episodes are increased up to 4-fold during the menopausal transition. This includes suicidal thoughts. Women are presenting to their healthcare providers with mood issues and they are given a selective serotonin reuptake inhibitor (SSRI) medication. Current evidence-based literature does not support the use of SSRIs for mood disturbances in women without a formal diagnosis of clinical depression. Women should ask about hormone therapy over antidepressant medications when presenting with mood disorders and brain fog in the perimenopause and menopausal transition. Current data shows that 25% of midlife women are taking SSRIs compared to 3-7% that are taking hormone therapy. Thanks again to the very flawed and misleading Women’s Health Initiative (WHI) that has changed the face of Women’s Healthcare for the past two decades.
Testosterone has been shown to improve libido and inflammation while having cardiac, bone and neuro protective properties. Women should be angry with the lack of support from governmental agencies, societal guidelines and discrimination between treatment options compared to men. Studies have shown that when men have low testosterone they experience fatigue, depression, mood disturbances, cognitive impairments and without treatment they have an increased risk of dementia. Testosterone replacement in men is generally covered by their insurance even though the only FDA indication for men is hypogonadism. Most men are using testosterone for fatigue, decreased libido and erectile dysfunction.
Women produce four times as much testosterone compared to estrogen. The obsession in hormone therapy centers around estrogen. Educating the patient has never been so important especially since most healthcare providers including OBGYNs never receive training in midlife issues and hormone therapy. If your provider tells you that hormones are BAD or that hormones cause cancer, they are not educated.
Back to the study in Europe by Glenn, Nusen and colleagues. The women included in the study were already on hormone therapy with estrogen alone or estrogen combined with progesterone. They were on natural hormones. They were not taking a synthetic hormone. The progesterone was micronized progesterone or an IUD, not a progestin. They had been on this therapy for at least 3 months and continued to have at least one mood or cognitive symptom and persistent low libido. They were placed on testosterone and in this study it was given transdermal (through the skin) and their estrogen dose was not changed.
**disclaimer, testosterone pellets were not used in this study even though they are considered transdermal.
A menopause symptom questionnaire was completed before the testosterone was started and again at four months. The aim of this study was to address persistent mood and cognitive issues in women who were already taking standard hormone therapy (estrogen with or without progesterone). Cognition symptoms that were addressed included feeling tired, lack of energy, memory, and concentration issues. Mood symptoms addressed included feeling tense, nervousness, irritability, anxiety, panic, depression, unhappiness, crying spells, loss of interest in most things and loss of interest in s*x. Does any of this sound familiar? Surveys have shown that most women do not feel comfortable asking their physician questions about these topics and most physicians are embarrassed or not trained in addressing these issues.
This study was completed in the UK and the transdermal preparations used included Androderm, Tostran and Testogel. The average dose was 5mg daily. The cohort included 510 women. This study was not orchestrated by a pharmaceutical company. The mean age was 54 with 67% of the women in menopause and 34% perimenopause. Libido was the most bothersome symptom at the start and cognitive symptoms were reported more than mood symptoms. Almost 60% of women reported improvements in crying spells, interest in activities and s*x. Memory improved in 35% of the women. Overall, moderate to severe symptoms were decreased by 33%.
Let’s simplify this medical jargon. In this group of 510 patients given testosterone therapy, significant improvement was reported in all mood and cognitive symptoms including frequency and severity. Libido was improved as well. Remember, libido is a mood! You will be in the mood for s*x if you are not fatigued, irritable, anxious or having a lot of negative mood symptoms.
The study concluded that testosterone therapy can benefit mood and cognition and can be combined with estrogen and progesterone therapy. This is data that we have known for almost 100 years, however, people want you to believe that we do not have any studies to support the use of testosterone in women. There was a double-blinded randomized (best type) study in 1985 showing that women who had undergone a hysterectomy with removal of their ovaries (surgical menopause) had more energy and overall improvement in their well-being when given testosterone with estrogen versus estrogen alone or a placebo. In my practice, I have found that testosterone lowers the dose of estrogen that is need by most patients. Another study in 1988 showed improved cognition scores in women treated with estrogen or estrogen and testosterone after hysterectomy and removal of ovaries. I mention these studies to reiterate that we had data prior to the Women’s Health Initiative showing the benefits of HRT. Prior to the WHI over 50% of women who were eligible for therapy were taking hormones. This has dropped to less than 10% (however, data is likely not accurate since women have turned to compounded options). The use of testosterone in women remains off-label (FDA approved for men with hypogonadism even though 75% of testosterone use in the US in men is being used off-label for libido and s*xual dysfunction).
Testosterone is not the cure all. It does not help everyone and dosing is individualized. In this study, levels were not checked and everyone received a standard 5mg dose daily. Not all women will achieve a therapeutic level with a standard dose. Thus the non-responders may have responded to an upward titration. Also, four months may not be enough time to make an assessment. Transdermal testosterone can take 3-6 months to reach steady state levels and may require titration to find the dose that works. One size (dose) does not fit all and not all women will metabolize and/or absorb the same. Not all libido is a hormone issue. Psychological evaluation and s*xual therapy may be needed as well.
Find a provider who is an expert in hormone therapy. Being a member of a menopause society or association does not make you an expert. Weekend courses do not prepare one for hormone management. They may teach a provider about menopause and treatment options, however, most courses do not allow a provider to become competent in prescribing hormones. Don’t get me wrong, there are reputable courses available in the US that actually prepare a provider for hormone replacement. Remember most healthcare providers including OBGYNs have not received any formal training in replacement therapy. Obviously, I am very passionate about hormone replacement, longevity, and wellness. I have spent more than two decades offering hormone replacement therapy. I initially trained under Dr. Charlton R. Vincent, MD in Laurel, MS (he trained directly under Robert B Greenblatt who introduced hormone pellet therapy to the US in 1939).
Be careful when a provider ONLY offers you hormone pellets. I am a provider that offers bio-identical hormone replacement therapy (BHRT) that includes pellets, however, I also utilize patches, creams, gels, and injectables. An oral (pill) form is available as well. However, while the oral form is inexpensive, there are risks to oral options that you will not have with transdermal options. We have approximately 400 pellet patients in our practice and most of them have either failed or did not like their response to other options. Many of them request pellets because of word of mouth from their family and/or friends or lastly, they want the convenient dosing. Pellets have been around longer than any other form of therapy (1937). I have women in my practice who have been getting hormone pellets for 50 years and some of my patients drove to Augusta, Georgia in the 70-80s to get their pellet therapy from Dr. Greenblatt. There is actually no such thing as too high of a dose of testosterone, however, the higher the dose and the higher the level, the more risk of side effects. Side effects typically include oily skin, acne, hair growth (excessive) and/or aggressiveness. Some women need a higher dose than others. Lastly, be wary of providers that perform labs (costly) every time you see them for treatment. We are treating symptoms. We are not treating a number.
Articles written on my page to not constitute the practice of medicine. No doctor-patient relationship is formed from this information. I recommend you talk to your healthcare provider about your perimenopause/menopausal symptoms and hormone replacement therapy. I am happy to establish a doctor-patient relationship with you at my office.
Dr DeSantis
