Effects of long term low estrogen states

An often used treatment for endometriosis is to lower the estrogen in a woman’s body via hormonal suppression. Birth control can mimic a pregnancy state, while other treatments, such as gonadotrophin-releasing hormone agonists (GnRHa), can mimic a menopausal state. So what does estrogen do in the body and why do they want to lower it? 

Estrogen not only affects the reproductive organs, but it also affects the heart and blood vessels, bones, breasts, skin, hair, mucous membranes, pelvic muscles, the urinary tract, and the brain (University of Rochester Medical Center Rochester, n.d.). All these different tissues have estrogen receptors (ER) on them that, when activated by estrogen, tell the cell how to behave. Endometriosis also has estrogen receptors. Estrogen, via these receptors, cause an increase in endometriotic “lesion size, fluid volume, increased epithelial cell height, and epithelial cell proliferation” (Burns et al., 2012). The thought is that by decreasing estrogen, the endometriotic lesions can be “tamed”, so to speak. However, estrogen still has receptors in all those other tissues and has an important role in the functioning of those other areas.

According to Medical New Today (De Pietro, 2018), low estrogenic states can have the following effects:

• “Weak bones: Estrogen helps keep the bones healthful and strong. As estrogen levels decrease, bone loss may occur. For example, women who are post-menopausal are at an increased risk of developing osteoporosis and bone fractures.
• Painful intercourse: Estrogen can affect vaginal lubrication. If levels become too low, vaginal dryness can occur, which often leads to painful sex.
• Hot flashes: Hot flashes often happen during menopause due to low estrogen levels.
• Depression: Estrogen is thought to increase serotonin, which is a chemical in the brain that boosts mood. Estrogen deficiency may cause a decline in serotonin that contributes to mood swings or depression.
• Increase in urinary tract infections: Increased urinary tract infections may occur due to the thinning of the tissue in the urethra, which can develop with decreased estrogen.”

The low estrogenic states induced by the medications can cause side-effects similar to menopause: “hot flashes/sweats, headache/migraine, decreased libido (interest in sex), depression/emotional lability (changes in mood), dizziness, nausea/vomiting, pain, vaginitis, and weight gain” (LupronDepot, n.d.). When estrogen is lowered to a chemically induced menopausal state for a long time, it can cause serious effects. “Regardless of the cause,…women who experience premature menopause (before age 40 years) or early menopause (between ages 40 and 45 years) experience an increased risk of overall mortality, cardiovascular diseases, neurological diseases, psychiatric diseases, osteoporosis, and other sequelae” (Shuster et al., 2010). The effect on bone health is why GnRHa medications are recommended as treatment for no longer than 12 months total therapy (two 6-month treatments)- “due to concerns about adverse impact on bone thinning” (LupronDepot, n.d.). This thinning of the bones “may not be completely reversible in some patients” (LupronDepot, n.d.). This should be considered and discussed with your provider when looking at long term options. 

When looking at effectiveness of treatment with hormonal medications:

“Combined oral contraceptive pills (COCP), GnRHa and progestogens are equally effective in relieving endometriosis associated pelvic pain. COCP and progestogens are relatively cheap and more suitable for long-term use as compared to GnRHa. Long-term RCT of medicated contraceptive devices like Mirena and Implanon are required to evaluate their long-term effects on relieving the endometriosis associated pelvic pain.” (Wong & Lim, 2011)

References

Burns, K. A., Rodriguez, K. F., Hewitt, S. C., Janardhan, K. S., Young, S. L., & Korach, K. S. (2012). Role of estrogen receptor signaling required for endometriosis-like lesion establishment in a mouse model. Endocrinology, 153(8), 3960-3971. doi: 10.1210/en.2012-1294

De Pietro, M. (2018). What happens when estrogen levels are low?. Retrieved from https://www.medicalnewstoday.com/articles/321064.php#diagnosis

LupronDepot. (n.d.). Lupron Depot for endometriosis. Retrieved from https://www.luprongyn.com/lupron-for-endometriosis

Shuster, L. T., Rhodes, D. J., Gostout, B. S., Grossardt, B. R., & Rocca, W. A. (2010). Premature menopause or early menopause: long-term health consequences. Maturitas, 65(2), 161-166. doi: 10.1016/j.maturitas.2009.08.003

University of Rochester Medical Center Rochester. (n.d.). Estrogen’s effects on the female body. Retrieved from https://www.urmc.rochester.edu/encyclopedia/content.aspx?ContentTypeID=85&ContentID=P00559

Wong, W. S. F., & Lim, C. E. D. (2011). Hormonal treatment for endometriosis associated pelvic pain. Iranian journal of reproductive medicine, 9(3), 163. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4575749/