Oligomenorrhea is infrequent (or, in occasional usage, very light) menstruation. More strictly, it is menstrual periods occurring at intervals of greater than 35 days, with only four to nine periods in a year. Menstrual periods should have been regularly established before the development of infrequent flow. The duration of such events may vary. Causes
Oligomenorrhea can be a result of prolactinomas (adenomas of the anterior pituitary). It may be caused by thyrotoxicosis, hormonal changes in perimenopause, Prader–Willi syndrome, and Graves disease. Endurance exercises such as running or swimming can affect the reproductive physiology of female athletes. Female runners, swimmers and ballet dancers either menstruate infrequently in comparison to non-athletic females of comparable age or exhibit amenorrhea. A more recent study shows that athletes competing in sports that emphasise thinness or a specific weight exhibit a higher rate of menstrual dysfunction than either athletes competing in sports with less focus on these or control subjects.Breastfeeding has been linked to irregularity of menstrual cycles due to hormones that delay ovulation. People with polycystic ovary syndrome (PCOS) are also likely to have oligomenorrhea. PCOS is a condition in which excessive androgens (male sex hormones) are released by the ovaries. People with PCOS show menstrual irregularities that range from oligomenorrhea and amenorrhea, to very heavy, irregular periods. The condition affects about 6% of premenopausal females. Eating disorders can result in oligomenorrhea. Although menstrual disorders are most strongly associated with anorexia nervosa, bulimia nervosa may also result in oligomenorrhea or amenorrhea.
Pharmacology
Compared to melphalan, melphalan flufenamide exhibits significantly higher in vitro and in vivo activity in several models of human cancer. A preclinical study, performed at Dana–Farber Cancer Institute, demonstrated that melphalan flufenamide induced apoptosis in multiple myeloma cell lines, even those resistant to conventional treatment (including melphalan). In vivo effects in xenografted animals were also observed, and the results confirmed by M Chesi and co-workers – in a unique genetically engineered mouse model of multiple myeloma – are believed to be predictive of clinical efficacy. Structure
Chemically, the drug is best described as the ethyl ester of a dipeptide consisting of melphalan and the amino acid derivative para-fluoro-L-phenylalanine. Pharmacokinetics
Pharmacokinetic analysis of plasma samples showed a rapid formation of melphalan; concentrations generally exceeded those of melphalan flufenamide during ongoing infusion. Melphalan flufenamide rapidly disappeared from plasma after infusion, while melphalan typically peaked a few minutes after the end of infusion. This suggests that melphalan flufenamide is rapidly and widely distributed to extravasal tissues, in which melphalan is formed and thereafter redistributed to plasma.This rapid disappearance from plasma is likely due to hydrolytic enzymes. The Zn(2+) dependent ectopeptidase (also known as alanine aminopeptidase), degrades proteins and peptides with a N-terminal neutral amino acid. Aminopeptidase N is frequently overexpressed in tumors and has been associated with the growth of different human cancers suggesting it as a suitable target for anti-cancerous therapy. Adverse effects
In a human Phase 1 trial, no dose-limiting toxicities (DLTs) were observed at lower doses.