More specifically, those steroids inhibit NADH (also known as DPNH) oxidation in the mitochondria, which shifts the mitochondrial NAD+/NADH ratio in favor of reduction, resulting in reverse electron transport, reactive oxygen species (ROS) generation, and, ultimately, some serious “named” condition (e.g. diabetes, CVD, cancer, etc) down the road. In addition, estrogen inhibits pyruvate dehydrogenase, which results in further inhibition of OXPHOS and even more accumulation of NADH, and thus a further drop in NAD+/NADH ratio. Finally, estrogen also apparently induces a multi-fold rise in ceruloplasmin – a reliable biomarker of both acute and chronic inflammation, as well as some cancers (e.g. lymphomas).
https://doi.org/10.1111/j.1532-5415.1963.tb00071.x
“…It is known that estrogens act catalytically in low concentrations at critical levels of cell metabolism. For example, diethylstilbestrol strongly inhibits the diphosphopyridine nucleotide oxidation that is normally carried out by enzymes from a variety of mammalian tissues, tumors and micro-organisms. The site of such inhibition has been localized in skeletal muscles to DPNH cytochrome C reductase (54a, b). This inhibitory effect enables small amounts to exert significant metabolic influences, even in tissues devoid of steroid enzymes…It was further noted that the glutamic dehydrogenase reaction was most susceptible to the effect of these hormones in the presence of the oxidized or reduced form of the oxidation-reduction cofactors (DPN, DPNH), and that the effect of steroid hormones could be completely reversed by the addition of adenosinediphosphate. It was also found that diethylstilbestrol has the property of inhibiting the pyruvate kinase which catalyzes the terminal step in glycolysis.”
“…Another example of the role of estrogenic substances in catalytic oxidation is their effect upon plasma copper transport and ceruloplasmin. In both normal volunteers and in certain cancer patients, it has been found that the ceruloplasmin level increases two to eight times ahove normal following stilbestrol administration (55).”
https://doi.org/10.1016/S0021-9258(18)64481-3
“…From another standpoint, we have recently reported (5) that catalytic concentrations of a number of steroids inhibited reduced diphosphopyridine nucleotide (DPNH) oxidases from many mammalian and microbial sources. a-Tocopherol (and other compounds found by Nason and Lehman (6) to reactivate isooctane-treated preparations of DPNH-cytochrome c reductase) could competitively reverse the steroid inhibition (5). In skeletal muscle, the site of inhibition yas shown to be the DPNH-cytochrome c reductase reaction. Jensen (7) also found that in heart sarcosomes, DPNH-cytochrome c reductase was inhibited by the adrenal cortical hormones. “
