Synthesis 1
Estradiol 3-methyl ether (1, EME) is partially reduced to the 1,5-diene (2) as also occurs for the first step in the synthesis of nandrolone. Oppenauer oxidation then transforms the C17β hydroxyl group into a ketone functionality (3). This is then reacted with metal acetylide into the corresponding C17α ethynyl compound (4). Hydrolysis of the enol ether under mild conditions leads directly to (5), which appears to be noretynodrel (although Lednicer states that it is "etynodrel" in his book (which may be a synonym etynodiol); etynodrel is with a chlorine atom attached), an orally active progestin. This is the progestogen component of the first oral contraceptive to be offered for sale (i.e., Enovid). Treatment of the ethynyl enol ether with strong acid leads to norethisterone (6).In practice, these and all other combined oral contraceptives are mixtures of 1 to 2% EE or mestranol and an oral progestin. It has been speculated that the discovery of the necessity of estrogen in addition to progestin for contraceptive efficacy is due to the presence of a small amount of unreduced EME (1) in early batches of 2. This when subjected to oxidation and ethynylation, would of course lead to mestranol (3). In any event, the need for the presence of estrogen in the mixture is now well established experimentally.
Dysplasia can be low-grade or high-grade. High-grade dysplasia may also be referred to as carcinoma in situ. Invasive carcinoma, usually simply called cancer, has the potential to invade and spread to surrounding tissues and structures, and may eventually be lethal. Examples
Cervical squamous intraepithelial lesion (SIL), previously called cervical intraepithelial neoplasia (CIN), is a form of dysplasia that can progress to cervical cancer. The term carcinoma in situ may be used interchangeably with high-grade SIL. Ductal carcinoma in situ of the breast is the most common precancer in women. Bowens disease is a squamous carcinoma in situ of the skin. Colon polyps often contain areas of CIS that will almost always transform into colon cancer if left untreated. High-grade prostatic intraepithelial neoplasia is equivalent to CIS of the prostate. Bronchioloalveolar carcinoma (BAC) of the lung is the only form of CIS that can kill directly because, in rare cases (the "pneumonic form"), it expands greatly and fills the lungs, preventing breathing and causing other dire effects on the host. Thus, the pneumonic form of BAC is a true malignant entity, but is not "invasive" in the classical sense. For this reason, it is considered a form of CIS by pathologists, but not by oncologists or surgeons, and inclusion of this form of cancer among the types of CIS is controversial. Treatment
Carcinoma in situ is, by definition, a localized phenomenon, with no potential for metastasis unless it progresses into cancer. Therefore, its removal eliminates the risk of subsequent progression into a life-threatening condition.