The name Dimera (pronounced with a long i) is chosen to highlight formation of molecule pairs, called dimers, that are the key step in activation of progesterone (as well as other) steroid receptors. You are welcome to visit here often, as you will find frequent updates to this website that highlight cardiovascular (CV) and related (smooth muscle) research progress in the "dimer" "era."
Progestin Drugs include Progesterone, and medroxyprogesterone acetate
The misunderstanding that the word "progesterone" might be a class of steroid compounds (as might be logically supposed because "estrogen" is the word meaning the whole class of estrogenic steroids) is a source of confusion. Progesterone is a single, specific chemical molecule. The words that should be used to refer to progestagenic compounds as a group are in fact "progestin" and "progestagen" (which are, by the way, synonymous) and "progestogen" (an alternative spelling). The synthetic progestin, medroxyprogesterone acetate (MPA), also known as Provera, Depo-Provera, and incorporated as the progestin in Prempro and Premphase (the most commonly prescribed USA postmenopausal hormone therapies), is a distinctly different chemical entity with biological actions on blood vessels very unlike the actions of progesterone.
Progesterone is an endogenous (naturally occurring) human hormone for which important beneficial gene level actions--previously unrecognized--have been discovered, and for which a threshold for normal function has been defined.
Yet progesterone is blamed, due to misunderstanding, but without evidence, for the sins of MPA.
The confused terminology is so pervasive that investigations of potential beneficial functions of progesterone have not been carried out, and thus the progress greatly delayed in answering fundamental questions related to the notion of essential roles of progesterone. Notice the 2004 Missmer Journal of the National Cancer Institute reference as an example. MPA (a 24 carbon steroid) was designed as a synthetically altered derivative of progesterone (a 21 carbon steroid) to allow convenient oral dosing and improved duration of action (as the half-life of bio-identical progesterone is only a matter of minutes). The only indication for MPA use tested was apparently the secretory transition in endometrium (of the uterus). Other actions (on blood vessel function, blood clotting, and breast cancer) were not adequately tested.
Non-oral formulations of safe, bio-identical steroids, introduced through the skin at low doses over many hours (as patches or creams), provide a more rational approach. The short half-life problem of progesterone in the blood is overcome, the extensive metabolism by the liver is avoided, drug metabolism enzyme induction is avoided, and many side effects are minimized (or eliminated) by using transdermal progesterone. The lower (than naturally occurs in a normal menstrual cycle) dose of transdermal progesterone studied in randomized, controlled pilot trials is now ready for Phase III FDA human clinical trials. The first drug designed to treat heart disease in women is at present only limited by sufficient capital to carry out Phase III trials.
Dimera has discovered and developed the concept of blood vessel hyperreactivity. In addition to plaques or clots that can block blood flow by physical obstruction, there can also be functional reasons for prolonged impaired blood flow (ischemia). Blood vessels function by dynamically constricting and relaxing to regulate blood flow. The heart, brain, and kidneys require nearly constant high blood flow while other areas, e.g., skin, skeletal muscle, and stomach, need higher blood flow for only short periods on demand. The blood flow to each organ is locally determined by vascular tone, which is organ specific and changing from moment to moment. Imbalances that occur during aging (such as excess expression of thromboxane-prostanoid receptors) can cause malfunctions of the multiple regulatory mechanisms that insure blood supplies to vital organs. Blood flow demand by running legs might, for example, conflict with those of the stomach when digesting. More serious problems would develop if demand by running legs diverted necessary blood from the heart.
Subtle--but important--deficiencies in blood flow can therefore result from an imbalance of vasoconstrictor or vasodilator responses to everyday situations. In a hypothetical hyperreactivity only explanation, there would be no structurally detectable indication of abnormality; consequently, diagnosis would be much more difficult. To explain further, the cause of the functional abnormality (ST segment changes, signs, and symptoms of coronary ischemia) could only be recognized in action (such as when provoked by injection of vasoconstrictors in the cardiac catheterization laboratory). Such vasoconstrictor catheterization tests are not routinely made (as they aren't needed for typical male presentations), and even if they could be, cost issues would limit dynamic measurements to only about 1% of those who may benefit.
However, solid evidence of constrictor hyperreactivity are accumulating from catheterization laboratories (i.e., slow flow, prolonged TIMI counts, or even transient (but ischemia-causing) disappearance of major coronary arteries from angiograms. Advances in cardiac diagnostic technology--namely, high strength magnetic resonance images (MRI)--are now proving ischemia (blood flow deficit). Microvascular angina (the dominant presentation in women) deficits can finally be detected--giving women previously suspected of having psychosomatic problems urgently needed peace of mind. High resolution MR has many virtues--e.g., can be non-invasive and never requires any radiation--from which a concept is emerging that appears to explain functional (other wise undetectable) coronary ischemia that we believe causes angina pectoris and cardiac symptoms. Patients in this ST segment changes angina group are decidedly not, as they are commonly labeled now, " false positives."