In a previous article I outlined a study showing the effectiveness of testosterone therapy on menopausal symptoms in pre- and post-menopausal women. Here I will present and comment on an insightful study that compared head-to-head the effectiveness of testosterone therapy and estrogen therapy in surgically menopausal women who had their ovaries removed.
Before the surgical removal of both ovaries (bilateral ovariectomy) women were randomly assigned to either a testosterone alone, estrogen alone, or placebo groups. There were 10 patients in each group.
Mean age of the women was 46 years. They had underwent bilateral ovariectomy due to having uterine fibroids (aka myoma), which are non-cancerous (benign) tumors that develop in the womb (uterus).
The testosterone group received injectable testosterone (enanthate); 200 mg/ml.
The estrogen group received injectable estradiol; 10mg/ml.
The testosterone/estrogen group received injectable testosterone (enanthate) 150 mg + 8.5 mg estradiol/ml.
All groups received 1 ml intramuscular injections every 28 days for 3 months.
Blood hormone levels.
Daily menopausal rating scale; tracks somatic and psychological symptoms daily.
Menopausal Index; tracks 26 symptoms most often reported by clinicians and by women themselves as being typical and frequent complaints around menopause. The questionnaire was filled out before the start of hormone treatment, and after each month, before each monthly blood draw.
The table shows the changes in testosterone and estradiol on the three treatment groups.
Energy level and wellbeing
During each of the treatment months, women in the estrogen-alone and placebo groups reported significantly lower ratings of energy level and wellbeing than the estrogen-testosterone group and the testosterone-alone group. Women in the testosterone-alone group reported highest ratings of energy level and wellbeing at all time points during the 3 month treatment period.
Menopausal Index scores
The effect on the Menopausal Index followed the same pattern as that of energy level and wellbeing. Lower scored indicate lower frequency and lower severity of symptoms. The testosterone-alone group reported lower symptom scores than the estrogen-testosterone group, which reported lower symptom scores than the estrogen-alone group and placebo groups. There was no difference between the estrogen-alone group and placebo groups.
This study unequivocally demonstrates the different response of physical and psychological symptoms to estrogen and testosterone treatment in surgically menopausal women. Testosterone treatment is superior for increasing energy levels and wellbeing and reducing menopausal symptoms, when compared to placebo, estrogen-alone and estrogen-testosterone treatment.
The superior functioning in the testosterone treated group occurred in association with significantly higher testosterone levels during the treatment.
The results in this study indicate that reduced levels of testosterone subsequent to surgical removal of the ovaries may play an important role in the development of the detrimental physical and psychological symptoms which are a common consequence of this surgical procedure.
This is one of the few studies that have compared testosterone therapy and estrogen therapy head-to-head. The finding that testosterone therapy is superior to both estrogen therapy and combined estrogen-testosterone therapy in improving energy levels, wellbeing and menopausal symptoms, is notable and relatively unknown.
The observation that testosterone therapy is superior to combined estrogen-testosterone therapy could be explained by treatment induced changes in SHBG (sex hormone binding globulin). Both estrogen and testosterone bind to SHBG, which transports steroids in the blood, and only the unbound fraction of hormones is biologically active. Estrogen increases SHBG levels while testosterone has the opposite effect. In addition, SHBG binds with higher affinity to testosterone than estradiol. Therefore, administration of testosterone alone in the presence of low estrogen levels will result in a higher percentage of free testosterone levels compared to combined estrogen-testosterone treatment. This relative increase in free testosterone levels in the testosterone-alone group likely explains its superior effects.
In this study estrogen therapy was not better than placebo. Conventional estrogen therapy is controversial, as studies show it doesn't always improve all symptoms and may have negative health effects.[5-9] The most serious concern about traditional estrogen HRT (hormone replacement therapy) is its potential to increase risk for breast and endometrial cancer, blood clots, stroke and heart disease. Nonetheless, bio-identical hormones are associated with lower risks, including the risk of breast cancer and cardiovascular disease, and are more efficacious than their synthetic and animal-derived counterparts. As of this writing, no study has compared bio-identical estrogen treatment with testosterone treatment. Even though bio-identical estrogen treatment may confer less risk for breast cancer than conventional estrogen treatment, estrogen is still contraindicated in women with a family history of breast cancer. Also, bilateral oophorectomy may have long-term negative consequences for heart disease risk factors not completely ameliorated by estrogen use.
Because the ovaries produce testosterone (even in post-menopausal women) and are a major contributor to testosterone levels in women.[13, 14] testosterone is especially important for women who have had their ovaries surgically removed. In line with this, data indicates that these women may need a higher dose of testosterone to achieve symptomatic improvements.
Can testosterone be expected to be a superior treatment in women with intact ovaries? While this study compared testosterone, estrogen and combined estrogen-testosterone treatments in women with surgically removed ovaries, there was a control group of women with intact ovaries. The testosterone treatment was superior when compared to the control group as well. Several other studies confirm the beneficial effects of testosterone-alone therapy on wellbeing and libido, in both pre- and post-menopausal women with intact ovaries. It has been demonstrated that testosterone therapy improves well-being, mood, and sexual function in premenopausal women with low libido [16, 17] as well as in naturally menopausal women.[15, 18] Thus, testosterone therapy confers benefits for women of all ages, with or without ovaries.
Accumulating research shows that testosterone therapy also may protect against breast cancer (more in this in an upcoming article). Therefore, because of the issues related to estrogen therapy, using testosterone therapy as the default choice of treatment for women who are suffering from low libido or menopausal and menopausal-like symptoms is justified.
1. Sherwin, B.B. and M.M. Gelfand, Differential symptom response to parenteral estrogen and/or androgen administration in the surgical menopause. Am J Obstet Gynecol, 1985. 151(2): p. 153-60.
2. Neugarten, B.L. and R.J. Kraines, "Menopausal Symptoms" in Women of Various Ages. Psychosom Med, 1965. 27: p. 266-73.
3. Pardridge, W.M., Serum bioavailability of sex steroid hormones. Clin Endocrinol Metab, 1986. 15(2): p. 259-78.
4. Anderson, D.C., Sex-hormone-binding globulin. Clin Endocrinol (Oxf), 1974. 3(1): p. 69-96.
5. Thomson, J. and I. Oswald, Effect of oestrogen on the sleep, mood, and anxiety of menopausal women. Br Med J, 1977. 2(6098): p. 1317-9.
6. George, G.C., et al., Effect of exogenous oestrogens on minor psychiatric symptoms in postmenopausal women. S Afr Med J, 1973. 47(49): p. 2387-8.
7. Barnabei, V.M., et al., Menopausal symptoms and treatment-related effects of estrogen and progestin in the Women's Health Initiative. Obstet Gynecol, 2005. 105(5 Pt 1): p. 1063-73.
8. Ortmann, O. and C. Lattrich, The treatment of climacteric symptoms. Dtsch Arztebl Int, 2012. 109(17): p. 316-23; quiz 324.
9. Marjoribanks, J., et al., Long term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev, 2012. 7: p. CD004143.
10. de Villiers, T.J., et al., Updated 2013 International Menopause Society recommendations on menopausal hormone therapy and preventive strategies for midlife health. Climacteric, 2013. 16(3): p. 316-37.
11. Holtorf, K., The bioidentical hormone debate: are bioidentical hormones (estradiol, estriol, and progesterone) safer or more efficacious than commonly used synthetic versions in hormone replacement therapy? Postgrad Med, 2009. 121(1): p. 73-85.
12. Kritz-Silverstein, D., E. Barrett-Connor, and D.L. Wingard, Hysterectomy, oophorectomy, and heart disease risk factors in older women. Am J Public Health, 1997. 87(4): p. 676-80.
13. Burger, H.G., Androgen production in women. Fertil Steril, 2002. 77 Suppl 4: p. S3-5.
14. Davison, S.L., et al., Androgen levels in adult females: changes with age, menopause, and oophorectomy. J Clin Endocrinol Metab, 2005. 90(7): p. 3847-53.
15. Davis, S.R., et al., Testosterone for low libido in postmenopausal women not taking estrogen. N Engl J Med, 2008. 359(19): p. 2005-17.
16. Goldstat, R., et al., Transdermal testosterone therapy improves well-being, mood, and sexual function in premenopausal women. Menopause, 2003. 10(5): p. 390-8.
17. Davis, S., et al., Safety and efficacy of a testosterone metered-dose transdermal spray for treating decreased sexual satisfaction in premenopausal women: a randomized trial. Ann Intern Med, 2008. 148(8): p. 569-77.
18. Panay, N., et al., Testosterone treatment of HSDD in naturally menopausal women: the ADORE study. Climacteric, 2010. 13(2): p. 121-31.