Progesterone Receptor Antagonists – A Novel Treatment for Severe Hyponatremia from the Endocrine Paraneoplastic Syndrome

Hyponatremia related to ectopic secretion of cancer cells of argininevasopressin (AVP) or atrial natriuretic peptide (ANP) is most commonlycaused by small cell lung cancer. The ideal treatment would be one thatnot only corrects the hyponatremia, especially if it is life threatening, butat the same time causes regression of the cancer, and thus improves bothquality and length of life. As one is waiting for chemotherapy, surgery,or radiotherapy to decrease the cancer burden, tolvaptan has been usedto correct the hyponatremia to improve symptoms or prevent death.Mifepristone, a progesterone receptor modulator/antagonist has been usedto treat various cancers. The oral 200mg tablet was given to an 80-year-oldwoman who developed sudden extensive lung cancer with a serum sodiumof 118 mmol/L. She refused chemotherapy but agreed to take mifepristone.The hyponatremia was completely corrected (145 mmol/L) within onemonth of treatment. She was in complete remission for 5 years and diednot from lung cancer, but an acute myocardial infarction. Mifepristonemay serve the purpose to not only quickly correct hyponatremia when itis related to an endocrine paraneoplastic syndrome, but also to provideimproved quality and length of life

Progesterone and Glucocorticoid Receptor Modulator Mifepristone (RU-486) as Treatment for Advanced Cancers

The fetal placental unit has paternal proteins which would normally result in immune rejection of fetus. Thus, to allow growth to 266 days, the mother must develop immunosuppressive proteins, cytokines, etc. to allow progression to a full-term baby. One of these essential immunomodulatory proteins is called the progesterone induced blocking factor (PIBF). Probably, the mechanism involved allowing the progesterone receptor antagonist mifepristone to cause termination of a pregnancy is by blocking the PIBF protein. There is good evidence that cancerous tumors borrow some of the same mechanisms as the fetus to escape immune surveillance, including the PIBF protein. Research data suggest that this protein is made and excreted by embryonic cells, mesenchymal cells, and trophoblast cells of the fetal placental unit to block the killing effect of natural killer cells and T-cells in the fetal microenvironment. Cancer cells do the same. Indeed, there is good evidence that mifepristone, a drug approved for pregnancy termination, can significantly improve length and quality of life in patients with various advanced cancers

Standards in semen examination:publishing reproducible and reliable data based on high-quality methodology

Biomedical science is rapidly developing in terms of more transparency, openness and reproducibility of scientific publications. This is even more important for all studies that are based on results from basic semen examination. Recently two concordant documents have been published: the 6th edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen, and the International Standard ISO 23162:2021. With these tools, we propose that authors should be instructed to follow these laboratory methods in order to publish studies in peer-reviewed journals, preferable by using a checklist as suggested in an Appendix to this article.Peer reviewe

A Hypothetical Model Suggesting Some Possible Ways That the Progesterone Receptor May Be Involved in Cancer Proliferation

Cancer and the fetal-placental semi-allograft share certain characteristics, e.g., rapid proliferation, the capacity to invade normal tissue, and, related to the presence of antigens foreign to the host, the need to evade immune surveillance. Many present-day methods to treat cancer use drugs that can block a key molecule that is important for one or more of these characteristics and thus reduce side effects. The ideal molecule would be one that is essential for both the survival of the fetus and malignant tumor, but not needed for normal cells. There is a potential suitable candidate, the progesterone induced blocking factor (PIBF). The parent 90 kilodalton (kDa) form seems to be required for cell-cycle regulation, required by both the fetal-placental unit and malignant tumors. The parent form may be converted to splice variants that help both the fetus and tumors escape immune surveillance, especially in the fetal and tumor microenvironment. Evidence suggests that membrane progesterone receptors are involved in PIBF production, and indeed there has been anecdotal evidence that progesterone receptor antagonists, e.g., mifepristone, can significantly improve longevity and quality of life, with few side effects

Hypo-Osmotic Swelling Test and Male Factor

For over 30 years, defects of the functional integrity of the sperm membrane, as evidenced by a low hypo-osmotic swelling test when evaluating the semen analysis, are not only associated with male infertility (even with sperm that otherwise seem normal), but unless corrected, successful intrauterine pregnancies will rarely ensue. This defect, interestingly, does not impair fertilization of the oocyte, but instead, prevents a normal-appearing embryo from successfully implanting. The frequency in infertile couples increases with advancing age of the male, ranging from 5% in younger males to 25% in men in their late forties or early fifties. It seems to be related to a toxic protein added to the sperm as they traverse the ejaculatory ducts. The defect is very correctable, either by treating the sperm with the protein digestive enzyme chymotrypsin prior to intrauterine insemination and avoidance of unprotected sex prior to ovulation, or in vitro fertilization with intracytoplasmic sperm injection. Unfortunately, this very inexpensive, easy-to-perform test is rarely performed by the large majority of physicians treating infertility. The purpose of this manuscript is to hopefully rekindle interest within the infertility community to add this test to the standard semen analysis

The Triad of Luteal Phase Ocular Migraines, Interstitial Cystitis, and Dyspareunia as a Result of Sympathetic Nervous System Hypofunction

Purpose. To evaluate whether ocular migraines can be related to sympathetic nervous system hypofunction, especially when associated with interstitial cystitis and dyspareunia. Materials and Methods: Dextroamphetamine sulfate was administered to a 34-year-old woman with a history of long-term interstitial cystitis, dyspareunia, and ocular migraines that were resistant to all other therapies. Results: In a short length of time the sympathomimetic amine therapy almost completely abrogated all of her symptoms and they have remained controlled while she continues on the drug. Conclusions: This is the first report of effectively treating ocular migraines with dextroamphetamine sulfate. The gynecologist should not be afraid to initiate therapy without referral to other specialists, especially if other symptoms of the sympathetic neural hyperalgesia edema syndromes exist, e.g., bladder pain of pelvic origin and dyspareunia

Marked improvement of vulvovaginitis of unknown origin in a pediatric patient - Case report

Materials and Methods: An eight-year-old girl with persistent severe vulvovaginitis of unknown origin also complained of unexplained weight gain and sudden academic difficulties. She was treated with dextroamphetamine sulfate.Results: She not only showed very quick and excellent relief from her vulvovaginitis but she also lost weight and improved her mentality.Conclusions: Sympathomimetic amine therapy may benefit pediatric vulvovaginitis when an infectious cause cannot be ascertained.Purpose: To present a novel therapy for pediatric vulvovaginitis