Hormone Replacement Therapy and OsteoporosisJuly 3, 2019
Can Testosterone replacement in men and Testosterone/Estradiol replacement in women help alleviate depression?
The World Health Organization states that depression is “the leading cause of ill health and disability worldwide.” It is twice as common in women and may be due to lower testosterone levels in women as compared to men. Depression increases by 2 to 4 times during perimenopause and menopause. The majority of patients with a Major Depressive Disorder have only a partial response or fail to respond at all, to SSRIs, the main category of medication used to treat depression (STAR*D Trial). To make matters worse, SSRIs decrease testosterone levels in the bloodstream.
Testosterone is very active in the brain and is known to increase memory, cognition, and mathematical ability. Testosterone replacement increases serotonin production and has been called by some “the happy chemical”.
Symptoms of testosterone deficiency may include not only depression but anxiety, anger, irritability, moodiness, decreased self confidence/self esteem, fearfulness, decreased libido and sexual function, decreased stress tolerance, fatigue and confusion.
Testosterone replacement therapy may help alleviate many of these symptoms. Before discussing the research in this area, the “Myths/Misconceptions” on Testosterone need to be reviewed.
Testosterone causes aggression.
Fact: Synthetic anabolic testosterone, commonly used and abused in very high doses by body builders and others, is known to increase aggression and rage. Bioidentical testosterone does not! High estradiol levels however can cause hostility and aggression. Research by Dr. Rebecca Glaser has shown that bioidentical testosterone pellets actually decrease aggression, irritability, and anxiety in over 90% of patients with low testosterone levels.
A pilot study by Dr. Karen Miller from Massachusetts General, found that transdermal testosterone therapy decreased the severity of depression by 67% in women with treatment resistant depression. Studies have also shown that estradiol therapy improves symptoms of anxiety/depression. One study by Dr. Susan Girdler revealed that approximately 32% of women develop clinically significant depression during menopause. This risk was decreased by 50% with the estradiol patch. Women with marked stress showed the most improvement in mood.
In a recent meta analysis of 27 clinical trials looking at testosterone therapy in men with depression, the authors stated “Testosterone treatment appears to be effective and efficacious in reducing depressive symptoms in men, particularly when higher-dosage regimens were applied in carefully selected samples.” Testosterone was found to be a moderate anti-depressant and helpful particularly in men who did not respond to standard antidepressants such as SSRIs. In fact, one study showed that the incidence of testosterone deficiency was 43% in men with treatment resistant depression. It was most beneficial at a higher dose and in men without a Major Depressive Disorder.
My own experiences in treating hormonal deficiency and imbalance in men and women have convinced me that hormonal therapy can be life-changing. I remember one patient who presented for consultation and was completely apathetic. She told me that the joy of living was absent from her life despite having a great marriage, successful children, a beautiful home and financial stability. 4 weeks after beginning hormone replacement therapy, she stated that we had “given her life back.” An 18 year old patient of mine, who I had delivered, suffered from severe depression and was on multiple antidepressants. Measurement of testosterone levels revealed deficiency (at an age when levels should have been high normal!) She was desperate and we began her on a trial of testosterone replacement. 4 weeks later, she had improved by 50%. A gentleman also recently presented with life debilitating anxiety. He was begun on testosterone pellet therapy and now rarely uses an anti anxiety medication!
Research has shown that the best and safest way to deliver hormones into the bloodstream is in the form of bioidentical hormone pellets. Hormone levels peak in 2 weeks (estradiol) and 6 weeks (testosterone) and then remain stable for 4 to 6 months. A baseline hormone panel can identify if you are hormone deficient. The risks and benefits of hormone replacement should be discussed with your doctor. During a one on one consultation with Dr. Cross, we spend 45-60 minutes and include a slide presentation on the basics of bioidentical HRT in men and women as well as coverage of specific topics including breast and prostate cancer, Alzheimer’s disease, cardiovascular disease, and osteoporosis.
R. Glaser, C. Dimitrakakis, “Testosterone therapy in women: Myths and misconceptions” Maturitas, 2013.
Andreas Walter et al, “Association of Testosterone Treatment with Alleviation of Depressive Symptoms in Men”, JAMA Psychiatry, Jan 2019.
Karen K. Miller et al, “Low-dose Transdermal Testosterone Augmentation Therapy Improves Depression Severity in Women” CNS Spectr. Dec 2009
Susan Girdler et al, “Can Hormone Therapy Prevent the Onset of Depressive Symptoms in Some Women Around Menopause?” JAMA Psychiatry, Jan 2018
T. Geracioti, “Persistent depression? Low libido? Androgen decline may be to blame” Current Psychiatry, May 2004
S. Shariat et al, “Systematic Review of the Impact of Testosterone Replacement Therapy on Depression in Patients with Late-onset Testosterone Deficiency” European Urology, July 2018
M. Cooper, “Testosterone Replacement Therapy for Anxiety” American Journal of Psychiatry, Nov 2000
K. Yazici et al, “The effects of hormone replacement therapy in menopause on symptoms of anxiety and depression” Turk Psikiyatri Derg, 2003
J. Smith et al, “Low Serum Testosterone in Outpatient Psychiatry Clinics: Addressing Challenges to the Screening and Treatment of Hypogonadism” Sexual Medicine Reviews, 2018
Dr. Cross graduated from Georgetown University School of Medicine in 1981. She completed her residency in Obstetrics and Gynecology at Naval Hospital San Diego in 1986 and received her board certification in Obstetrics and Gynecology in 1988, becoming a Fellow in the American College of Obstetrics and Gynecology in 1989. She is the Medical Director for Hormone Therapy of Citrus County and has also served as the Medical Director of Hormone Therapy Centers of America in Dallas, Texas. Dr. Cross continues to teach physicians across the country about Bioidentical Hormone Replacement.