Female Diseases

Ovarian dysfunction has been treated successfully by cell transplantation for decades, but it has mostly involved patients with physiological menopause. In the last thirty years, hormone replacement therapy by estrogen and progesterone has become the treatment of choice for menopause. Today, a growing concern that estrogen causes a variety of side effects, including cancer, brings back the fact that cell transplantations are safer than aspirin and do not cause cancer. In principle, stem cell transplantation of the ovary, placenta, adrenal cortex, hypothalamus thyroid epiphysis entire pituitary including the infundibulum, and the pineal gland is recommended.

Premature Menopause, where conventional hormone replacement therapy has failed, is another group of diseases where stem cell transplantation was used during the last thirty years with remarkable effectiveness. The number of patients with early menopause treated by stem cell transplantation cannot be compared with those undergoing normal “menopause.” [2].

The frequency of premature menopause has been increasing at such a rate that some consider it to be a real “epidemic.” It is apparently due to the stress and pressure of doing high-level jobs, among other things, requiring long hours, intense competition, hectic lifestyle, etc., along with the so many women in their early thirties stop menstruating, and soon develop classical symptoms of menopause, of its accompanying complications, In many instances it can be caused by prolonged use of birth control pills, The high incidence of genital infections among the young people of our modern society plays an unspoken part as well.

Physiology of Female Sex Hormones

The gonadotropin-releasing hormone of the hypothalamus stimulates the release of follicle-stimulating hormone (FSH) and luteotropic hormone (LH) from the anterior lobe of the pituitary in pulses.

In females, FSH supports the maturation of follicles and estrogen production in the granulosa cells of follicles. Estrogen stimulates the first additional release of gonadotropins up until the full maturation of follicle and creation of corpus luteum, i.e. positive feedback, but from that point on inhibits a further release of gonadotropins, i.e. negative feedback.

LH triggers ovulating and supports the creation of corpus luteum at mid-cycle, and corpus luteum produces progesterone, which inhibits any further release of gonadotropin as well, as a result of inhibition of gonadotropin release the concentration of estrogens and progesterone decrease that lead to menstruation.

Theca cells of the corpus luteum also produce androgens.

Estrogen stimulates the development of primary female sexual characteristics, i.e. change of Muller ducts into the Fallopian tube, uterus, and vagina, as well as secondary female sex characteristics, i.e. mammary glands, fat distributions, axillary and pubic hair growth (along with androgens), psychic development toward femineity. In the uterus they stimulate mucosal proliferation, in the uterine cervix and vagina lower the viscosity of cervical mucus and thicken vaginal mucosa, and break down glans estrogens to support the development of mammary ducts. They support the production of protein, HDL, and VLDL, and inhibit levels of LDL, thereby lowering the risk of atherosclerosis. Estrogens increase blood coagulation, retention of salts by kidneys, and bone mineralization.

Progesterone supports the uterus, the maturation and secretory activity of mucosa, and the contractility of musculature, and inhibits the motility of Fallopian tubes. In the uterine cervix again, they increase the viscosity of cervical mucus, narrow the cervical canal, inhibit the proliferation of the vaginal epithelium, and in the mammary glands support the development of alveoli. They increase the basal metabolic rates, body temperature, trigger hyperventilation and lower the sensitivity of peripheral cells to insulin, and decrease the production of cholesterol and plasma concentration of HDL and LGL,

Lack of estrogens and progesterone is often due to lowered release of gonadotropin-releasing hormone (excessive stress, port nutrition, professional sports, serious systemic diseases, neurotransmitter dysfunction) or gonadotropins (hemorrhage, infarction, inflammation, trauma of pituitary glands).

With growing ovarian production of androgens, the release of FSH is inhibited, and the maturation of follicles is blocked, leading to polycystic ovaries.

Decreased release of gonadotropins is often caused by an increased concentration of prolactin due to prolactin-producing tumors, lack of inhibition of prolactin secretions, anti-dopaminergic drugs, or by hypothalamic damage: trauma, radiation, degenerative or inflammatory diseases, and defects of biosynthesis.

Decreased production of estrogens and progesterone by ovaries can be due to developmental anomalies of ovaries, damage from radiation or cytostatic, or enzymopathy.

The lack of female sex hormones makes a normal menstrual cycle impossible, and the same applies to the excess of sex hormones, usually a result of contraception drugs. With the lack of estrogen, no proliferative phase in the uterine mucosa, and thereby progesterone cannot bring it to maturation, in either case, the females are very infertile. There is amenorrhea, less pronounced secondary sexual characteristics, a tendency towards vaginal infections, osteoporosis, and increased risk of atherosclerosis.

Gynecologists have observed that for some reason approximately 50% of patients with early menopause do not respond well to the usual hormone replacement therapy with estrogen and progesterone.

In the April 1994 issue of the Bulletin of Experimental Biology and Medicine, V117, an official journal of the Russian Academy of Medical Sciences, there were three articles about the results of a controlled study of the treatment of post-castration syndrome, i.e. “early menopause,’ by transplantation of human fetal tissues as compared with hormone replacement therapy and the controlled group [3 – 4}

The controlled study, actually a dissertation for a “Doctor of Science” degree at the Russian Research Center of Obstetrics Gynecology and Perinatology of the Ministry of Health of the Russian Federation, included 150 patients from 33 to 43 years of age, who underwent a bilateral total oophorectomy for a variety of indications, not including cancer, and were in early menopause and their ovaries were nonfunctioning as evidenced by ultrasound. Of this group, 45 patients were treated with human fetal tissue transplantation, 50 patients with hormone replacement therapy, and 55 patients received a placebo. Cell transplantation of the ovary, adrenal cortex, hypothalamus, placenta, spleen, and liver, had a 100% success rate.

The very comprehensive study included measurements of bone density, evaluation of central nervous system function and autonomous nervous system functionality, and breast examination [3 -4]

Female Infertility - there are clinical situations when in-vitro fertilization repeatedly does not work, for reasons that can’t be elucidated by even the most sophisticated diagnostic methods, in our experience, stem cell transplantation of the ovary, adrenal cortex, hypothalamus, placenta, the liver is to be considered in such instance followed in 4 weeks by another invitro fertilization attempt. Even though the medical reports about such an approach are hard to find, this has been a well-guarded secret of many gynecologists dealing with infertility long before invitro fertilization came into existence.

One study titled “Habitual Abortion of Adrenal Etiology via Porcine Stem Cells” reported a 96% success rate (22 of 23 patients delivered healthy children via routine application of adrenal cortex hormones with no risk to the mother or fetus.)

Habitual abortion due to impaired adrenal function is found in 26.6% of patients with delayed diagnosis and 15% to 20% of patients when the diagnosis was known before conception or in early pregnancy. The most common causes of habitual abortion are genetic 21-hydroxylase or 11-hydrolase deficiencies and Addison’s disease. The standard treatment using glucose and mineral corticoids is fraught with the risk of development defects of the fetus, in particular cleft lip and palate, when the treatment had to start in the first trimester of pregnancy or of overall growth retardation when the treatment had to be continued during the entire pregnancy – with the frequency of side effects ala glucocorticoids usage nearly 50%.

During 5 years, 23 patients from 22 to 38 years of age, with a history of 1 to 9 spontaneous abortions, diagnosis of Addison’s disease in 12 patients, or congenital hypercorticism with hyperandrogenism in 11 patients, all with threatened abortions, underwent stem cell transplantation of porcine adrenal cortex, prepared by tissue culture method at various stage of pregnancy (5 to 31 weeks) with implantation administered under aponeurosis of rectus abdominis muscle – with healthy, full-term deliveries (average 6 lbs, 14 oz) took place in 22 of the pregnancies. One patient had a spontaneous abortion at 16 weeks. Cortisol levels in the late stages of pregnancy were normal [1].

Bibliography

1. Egorov, YI, Marshalko, IV, Orlov, VI, Molnar, EM. Experimental treatment of habitual abortion of adrenal etiology by transplantation of tissue culture of new pig adrenals, Bull Exp Biol Med 1994; 117:389-39.
2. Holmer, AJM, Implantation von embryonalen Eierstocksgewebe in Fallen vo gonadaler Atenesie. (Implantation of embryonic ovarian tissue in case of agenesis of ovary). Genurtsh u Frauenhk. 1958;18: 621-626
3. Vortser, R Zur Siccacell-Behandlung von Amenofhoe und Steriltat. (About Siccacell treatment of amenorrhea and sterility). Hippocrates, Stuttgart 1958; 29:565-570
4. Alikhanova, ZM, Treatment of patients with post-castration syndrome by transplantation of human fetal tissues. (Kulakov VIZ), and International Institute of Biological Medicine, (Molnar EM), Moscow, 1995
5. Kulakov, VI, Alikhanova, ZM, Burdina, LM, Molnar, EM. Status of the breasts in patients with the post-castration syndrome treated by transplantation of human tissue. Bull Exp Bio Med 1994