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What are your thoughts on assessing testosterone in a Postmenopausal patient not on Testosterone replacement, is the LS/MS [LC-MS/MS] methodology recommended?

Assessing testosterone levels in postmenopausal women may be warranted following a review of relevant signs and symptoms. The mass spectroscopy method is the gold standard for measuring steroid hormones.

Hormone levels can be monitored during the perimenopausal period to help identify the stages of menopause, including estrogen, progesterone, testosterone, AMH, FSH, LH, and DHEA. Postmenopausal biomarker monitoring can also be valuable, and measuring testosterone may be warranted.

Please review the ODX Whitepaper on menopause. Below are excerpts that are relevant to the question at hand.

Cardiovascular Risk in Menopause

The relationship between sex hormones and CVD risk is not entirely clear and research is ongoing. Data from 2,834 postmenopausal women in the Multi-Ethnic Study of Atherosclerosis (MESA) were evaluated for their association with heart disease. Results indicate elevated testosterone (T) and an increased ratio of testosterone to estradiol (E2) were associated with an increased risk of cardiovascular disease and heart failure (Zhao 2018).

A cross-sectional study of 444 postmenopausal women revealed a significant association between the severity of symptoms and serum triglycerides, testosterone, and progesterone (Kaya 2017).

  • Elevated triglycerides were associated with severe symptoms
  • Past research also notes elevated triglycerides correlate with depression, decreased sexual desire, dry skin, and increased sweating.
  • High levels of testosterone were associated with severe psychological symptoms and total MRS scores.
  • Low progesterone was associated with severe symptoms.
  • Decreased progesterone may be associated with increased urogenital, psychological, and total menopausal symptom scores.

Increases in glycation end-products (AGEs) and other oxidative stress biomarkers are observed with menopause and associated with an increased risk of subclinical atherosclerosis. Significantly higher AGEs were observed in women with higher testosterone of 53-60 ng/dL (1.7-5.6 nmol/L) versus lower testosterone of 23-52 ng/dL (0.8-1.8 nmol/L) (Honour 2017).

Increased free androgen index (FAI), was also associated with increased AGEs. The correlation remained highly significant even after adjustment for HOMA-IR, fasting glucose, fasting insulin, age, and BMI (Diamanti-Kandarakis 2010).

Sex Hormone Binding Globulin in Menopause

A prospective longitudinal cohort study of 172 women found that while testosterone did not change from the pre- to postmenopausal period, SHBG decreased by 43% from 4 years prior to their final menstrual period to two years after. This shift increased the free androgen index by 80% during this period. The decreased SHBG and increased FAI correlated with an increase in BMI. Lower levels of DHEAS were also associated with a higher BMI (Burger 2000).

Decreased SHBG and higher BMI are associated with an increased risk of metabolic syndrome in postmenopausal women. Evaluation of data from the Women’s Health Study revealed that 51% of postmenopausal women, not on hormone therapy, met the criteria for metabolic syndrome. This group had significantly lower SHBG, higher BMI, more cardiovascular events, and significantly higher estradiol, testosterone, and free androgen index (Weinberg 2006).

Monitoring biomarkers associated with menopause and cardiometabolic comorbidities would be prudent and should include estradiol, progesterone, testosterone, DHEA, SHBG, FSH, AMH, lipids, leptin, adiponectin, vitamin D, thyroid markers, inflammatory markers, homocysteine, oxidative stress markers, and bone markers.

Laboratory method

The LC-MS/MS is a mass spectrometry method of measuring hormones is considered the gold standard. Researchers note that:

The increased sensitivity and specificity, along with multi-steroid analysis capability, grants MS-based methodologies a large advantage over the more widely-used immunoassays. As such, clinical societies and the CDC recommend the use of MS-based methods for therapeutic monitoring of steroid hormones in patients” (Conklin 2020).

References

Burger, H G et al. “A prospective longitudinal study of serum testosterone, dehydroepiandrosterone sulfate, and sex hormone-binding globulin levels through the menopause transition.” The Journal of clinical endocrinology and metabolism vol. 85,8 (2000): 2832-8. doi:10.1210/jcem.85.8.6740 [R]

Conklin, Steven E, and Claire E Knezevic. “Advancements in the gold standard: Measuring steroid sex hormones by mass spectrometry.” Clinical biochemistry vol. 82 (2020): 21-32. doi:10.1016/j.clinbiochem.2020.03.008

Diamanti-Kandarakis, Evanthia et al. “Androgens associated with advanced glycation end-products in postmenopausal women.” Menopause (New York, N.Y.) vol. 17,6 (2010): 1182-7. doi:10.1097/gme.0b013e3181e170af [R]

Honour, John W. “Biochemistry of the menopause.” Annals of clinical biochemistry vol. 55,1 (2018): 18-33. doi:10.1177/0004563217739930 [R]

Kaya, Cihan et al. “The relation among steroid hormone levels, lipid profile and menopausal symptom severity.” Journal of psychosomatic obstetrics and gynaecology vol. 38,4 (2017): 284-291. doi:10.1080/0167482X.2017.1321633 [R]

Zhao, Di et al. “Endogenous Sex Hormones and Incident Cardiovascular Disease in Post-Menopausal Women.” Journal of the American College of Cardiology vol. 71,22 (2018): 2555-2566. doi:10.1016/j.jacc.2018.01.083 [R]