Cyclical Gonadal Hormones
Cyclical Gonadal Hormones
Induction of Menstrual Cycle Associated Natural Killer Cell Surges
A female, after puberty, is almost immune to cancer before reaching the age of 40. Exceptions include a few breast cancers, some lymphomas, and a small diversity of other cancers. During reproductive years, (age 13 – 40) female physiology is characterized by ovulatory (menstrual) cycles and numerous other rhythmical cycles, such as puberty itself, diurnal cycles (sleep at night, awake during day), respirations, heart beat, brain waves, etc. During menstrual cycles, the maximum resistance to cancer occurs mid cycle after 12 – 14 days of estrogen, around the time of ovulation.
William J. M. Hrushesky, M.D., has studied and described in several peer reviewed papers and in a book* marked fluctuation in natural killer (NK) cell activity and resistance to breast cancer during menstrual cycles of the premenopausal women.
Hrushesky has also reported a marked difference in survival of breast cancer patients as a function of the time of the menstrual cycle when breast cancer resection was carried out.
Dr. Hrushesky has not, however, documented the mechanism of causation for the synchrony and covarience of immune surveillance peaks and ovulation which he has observed. Remaining unanswered is the mechanistic question, “Is this covarience a co-dependence on some common central cause, or, in the alternative, is the NK spike substantially derivative of the ovarian hormonal secretions: i.e. do the hormones associated with the menstrual cycle induce, at the time of ovulation, the clinically documented NK lymphocyte surge.
How are these cycles created? The brain is an elaborate computer. The command to the human brain to precipitate ovulation is 12 – 14 days of estrogen, a hormone secreted by the ovary under the inducement of the brain. NK peaks are associated with high serum peaks of estrogen and follicle stimulation hormone (FSH), and a cyclical high in luteinizing hormone (estrogen induced LH spike). LH, like growth hormone (GH), has been documented to be a powerful stimulant of NK cells.
Thus the brain is a computer that regulates immune surveillance (the normal ability to destroy early cancer), among its many many other non-conscious cyclical functions. What Dr. Smith has observed is that clinical employment of hormones made by the ovary, estrogen and progesterone, is able to induce cyclical fluctuations in NK count, strongly supporting the conclusion that these two hormones in youthful otherwise normal premenopausal females cause or are a major contributing cause of the cyclical intensifications of immune surveillance observed during menstrual cycles.
For an operative immune resistance to cancer, a patient must have three distinct systems intact:
A recognition “spotter” function
This function provides the mechanism whereby cancer cells may be discriminated from normal tissues. Basic research indicates such a function to be present in three types of cells: B-lymphocytes, dendritic cells, and macrophages.
Macrophages are scavenger cells capable of consuming dead cells, recognizing “spotting” foreign antigen (cancer) and presenting this foreign tumor antigen to the lymphocytes in an acceptably formatted manner. The B-lymphocytes which are presented foreign antigen — that part of the cancer cell that “looks” different from normal cell — then facilitate the immune surveillance process by the manufacture of tumor specific antibody based on the information (prepared tumor antigen) arriving directly or indirectly from the macrophages. Cancer specific antibody, once produced by the B-cells, then circulates through the body until it contacts cancer cells where it becomes attached. This antibody serves as a recognizable label on the foreign enemy cancer cells which, for attack purposes, have been “designated” or “targeted” for destruction by the natural killer and antibody activated killer cells.
A destroy “killer” function
This activity appears to operate by way of natural killer lymphocytes (NK cell) and related lymphocytes. NK cells are enabled or empowered to perform effectively by growth hormone (GH) and luteinizing hormone (LH):
(a) The command for the brain to produce an LH surge is 10 days to two weeks of estrogen. In pre-menopausal women this surge causes (1) ovulation and, (2) a large increase in NK lymphocyte counts and host mediated cancer resistance.
(b) Estrogen is a NK function suppressor; therefore when employed as an immune stimulant, estrogen should not be given for more than two weeks at a time.
(c) Progesterone, the hormone secreted by the ovary after ovulation, if administered immediately after the estrogen induced LH surge, induces a further increase in LH secretion, and is, therefore, a useful tool in interventions designed to augement / restore immune surveillance. Medroxyprogesterone acetate (Provera) for 10 days, and initiated after the end of an initial 14 day Premarin cycle, completes simulation of the Hrushesky circadian gonadal hormone cycle wherein large NK surges and large cancer resistance surges are well documented in the youthful female and in experimental animals.
(d) In cancer patients over the age of 40, estrogen typically induces prolactin secretion, whereas in early adulthood, estrogen is a direct GH secretagogue. Prolactin, secreted in large amounts during pregnancey, causes breast enlargement and immune suppression. Unborn babies are “tumors” and immune suppression to neoplasms is part of the essential physiology of pregnancy. Bromocriptine is a powerful regulator of the cell population that produces prolactin and GH. Bromocriptine (Parlodel) blocks prolactin secretion and stimulates GH secretion.
An Administrative, Management, and Regulatory System
This system is substantially the province of the helper T-lymphocytes. Helper lymphocytes are the cells known to decline in AIDS, and the AIDS related decline is associated with greatly increased susceptibility to infection and cancer. The entire lymphocyte series is substantially controlled by the thymus gland and its hormones. The thymus is subject to enabling restriction without growth hormone (GH). Bromocriptine (Parlodel) and pharmacological doses of vitamin C typically induce, over time, an increase in strength and stamina. This effect appears to arise from the ability of this combination to stimulate GH and is associated with rises in helper T-lymphocyte counts.
* Circadian Cancer Therapy, William J.M. Hrushesky, editor, CRC Press, 1994, 292 pages. At the time this book was published, Dr. Hrushesky was the Senior Attending Oncologist at the Stratten Department of Veterans Affairs Medical Center and Professor of Medicine at Albany Medical College. Dr. Hrushesky’s bibliography includes more than 200 scientific papers.