Announcing The Progesterone Metabolites Profile, the Newest Test in the Fight Against Breast Cancer
January 2nd, 2019
Meridian Valley Lab now measures progesterone metabolites in blood or bloodspot to provide insight into a possible hormonal basis for breast cancer risk.
Why test Progesterone Metabolites?
Breast cancer is the most common cancer in women worldwide and the leading cause of cancer-related death among women in the United States.
In addition to inherited predispositions and environmental and lifestyle factors, there is a positive association between lifetime exposure to estrogen and breast cancer risk. The role of progesterone on the other hand, in increasing breast cancer risk is not as clear cut but has largely been attributed to the use of synthetic progestins [1,2].
Systematic long-term human in vivo studies examining the effect of bioidentical progesterone on breast cancer risk is in its infancy [3,4]. Recent in vitro research using normal and breast cancer cell lines suggest that there is a definable difference in progesterone metabolism in situ between these cell lines. This difference may be an important risk factor for the development and progression of breast cancer [5,6].
Breast tissue can convert progesterone into two classes of metabolites: the -4-pregnenes have been shown in tissue studies to inhibit cell proliferation and detachment. The 5α-pregnanes stimulate breast cell proliferation and detachment. Meridian Valley Lab measures the following progesterone metabolites: Progesterone, 20α-dihydroprogesterone (20αHP), 3α-dihydroprogesterone (3αHP), 5α-dihydroprogesterone (5αP).
3αHP and 20αHP result from direct conversion of progesterone), catalyzed by the reversible enzymatic actions of 3α- and 20α- hydroxysteroid dehydrogenase, respectively. 5αHP is formed by the irreversible action of the enzyme 5α-reductase.
Both classes of metabolites are prevalent in tumorous and non-tumorous breast tissue. The proportion of each differs according to cancerous or healthy tissue and this might influence breast neoplasia and malignancy. In tumorous breast tissue, 5α-reductase enzyme activity is high resulting in a higher local concentration of 5α-HP, compared to 3αHP and 20αHP. In normal breast cells it is the opposite. The activity of 3α- and 20α- hydroxysteroid dehydrogenase is high with a higher local concentration of 3α-HP and 20α-HP compared to 5α-HP.
Furthermore, estradiol has been shown in vitro to increase 5αP receptor density with a concomitant decrease in 3αHP receptor density in the breast cell plasma membrane. An increase in 5αP receptor density is further enhanced by 5αP itself. 3αHP can block this estradiol-mediated increase in 5αP receptor density if present in sufficient amounts [7].
Despite the evidence which is limited to in vitro studies, measuring the progesterone metabolites in a patient may prove clinically important to guide treatment. Addressing non-modifiable (e.g.: genetics) and modifiable breast cancer risk factors (e.g.: diet and lifestyle) are also important in order to balance the impact hormone replacement therapy can have on cancer growth.
References:
[1]Fournier A, Berrino F, Riboli E, et al. (2005). Breast cancer risk in relation to different types of hormone replacement therapy in the E3N-EPIC cohort. International Journal of Cancer; 114:448-454.
[2]Fournier A, Berrino F, Chapelon FC. (2008). Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. Breast Cancer Research and Treatment; 107:103-111.
[3]Fournier A, Mesrine S, Dossus L, et al. (2014). Risk of breast cancer after stopping menopausal hormone therapy in the E3N cohort. Breast Cancer Research and Treatment; 145:535-543.
[4]Fournier A, Fabre A, Mesrine S, et al. (2008). Use of different postmenopausal hormone therapies and risk of histology- and hormone receptor- defined invasive breast cancer. Journal of Clinical Oncology; 26(8): 1260-1268.
[5]Wiebe JP. (2006). Progesterone metabolites in breast cancer. Endocrine-Related Cancer; 13: 717-738.
[6]Wiebe JP, Beausoleil M, Zhang G, Cialacu V. (2010). Opposing actions of the progesterone metabolites, 5-dihydroprogesterone (5P) and 3-dihydroprogesterone (3P) on mitosis, apoptosis, and expression of Bcl-2, Bax and p21 in human breast cell lines. Journal of Steroid Biochemistry & Molecular Biology; 118:125-132.
[7]Wiebe JP, Lewis MJ, Cialacu V, et al. (2005). The role of progesterone metabolites in breast cancer: Potential for new diagnostics and therapeutics. Journal of Steroid Biochemistry & Molecular Biology; 93:201-208.
