A common component of each of these conditions is mitochondrial dysfunction.
When we eliminate estradiol with medications such Lupron and other GnRH agonists or antagonists, or when we remove a woman’s ovaries, depleting her primary source for estrogen synthesis, metabolic flexibility diminishes significantly.* With the lack of metabolic flexibility comes a number of health issues, some noticeable, like weight gain, and others less noticeable, at least initially, like cardiac and neurodegenerative diseases. Estradiol, the most frequently studied among the steroid hormones, plays a pivotal role in determining how food fuel is converted into cellular fuel or ATP. Steroid hormones regulate metabolic flexibility at the level of the mitochondria. Steroid Hormones and Metabolic Flexibility: A Critical Factor in Post Lupron and Post Oophorectomy Ill Health Estradiol is simply where most of the research is focused, and so, it is where I too must focus, at least for the time being. Moreover, the chemical castration induced by Lupron and other medications or via ovary removal disrupt and diminish synthesis of a myriad of hormones. In this post, I will be digging even deeper into the role of estradiol in mitochondrial functioning, especially it’s role in something called metabolic flexibility.Ī note of caution, while I focus on estradiol, the mitochondria, and what happens to health when we remove estradiol pharmaceutically via Lupron or surgically via oophorectomy, it is important to remember that estradiol is not the only hormone synthesized in the ovaries nor are the ovaries the only hormone producing tissues. Could Lupron mediated mitochondrial damage be at the root of these side effects? Quite possibly? A question that remains is how. Digging a little deeper, the next post ( Lupron, Estradiol and the Mitochondria) pondered the connection between estradiol depleting drugs such as Lupron, other Lupron-like drugs and the devastating side effects that often follow suit. In the first post Hormones, Hysterectomy and the Aging Brain, we learned that estradiol depletion wreaks havoc on brain mitochondria turning them into misshapen donuts and blobs. At present, prevention of stroke should involve proven risk reduction strategies.Over the last several weeks, I have been looking at the role of estradiol in mitochondrial health. Despite the known neural and vascular benefits of estrogen, it is uncertain whether HRT is associated with stroke protection. In light of these contradictory data, several recent reports were highly significant (Nurses' Health Study, HERS Study, Cancer Prevention II Trial, WEST Trial). Several large-scale epidemiological studies have verified the concept of primary protection of stroke by HRT, though others have failed to do so. In animal models of stroke, estrogen induced anti-ischaemic effects. Estrogens may enhance cerebral blood flow and reduce vascular resistance. The width or thickness of the carotid wall is a good indicator of carotid atherosclerosis it increases after the menopause transition, and decreases with HRT. Abundant experimental data exist indicating that estrogens have both anti-atherosclerotic and neuroprotective effects.
As for blood pressure, a major detrimental risk factor for stroke, it is probably not affected by either the menopause per se or by HRT. The menopause metabolic syndrome, which includes weight gain and changes in lipids, insulin resistance, endothelial dysfunction, increased levels of homocysteine, lipoprotein (a) and several coagulation factors, may in part be attributable to estrogen deficiency, and may be reversible with hormone replacement therapy (HRT). As with coronary artery disease, the incidence of stroke rises after the menopause, in parallel with metabolic changes that add up to create an unfavourable risk factor profile for cardiovascular disease. Stroke is a leading cause of disability and death in women, despite progress in its prevention and treatment.