Pituitary-ovarian Dysfunction Research Articles

Panax ginseng Ameliorates Pituitary-Ovarian Dysfunction Induced by Radiofrequency Electromagnetic Radiation from Cell Phones via Upregulation of the CREM Signaling Pathway.

Panax ginseng (PG) is a plant that contains ginsenosides, which are considered adaptogens that confer cellular protection. However, the impact of PG on pituitary-ovarian dysfunction and subsequent infertility is unknown. This study investigated the hypothesis that PG would attenuate pituitary-ovarian dysfunction associated with mobile phone's Radiofrequency Electromagnetic Radiation (RF-EMR) in experimental rat models and the possible involvement of a cAMP Response Element Modulator (CREM)-dependent pathway. Twenty adult female Wistar rats were divided randomly into four groups, each consisting of five rats. The control group was administered a vehicle (distilled water) orally, while the P. ginseng group received 200 mg/kg of P. ginseng extract orally. The RF-EMR group was exposed to 900MHz radiation, and the RF-EMR + PG group was exposed to the same radiation while also being treated with 200 mg/kg of P. ginseng orally. These treatments were administered daily for a period of 56 days. The RF-EMR group exhibited significant reductions in serum levels of LH, FSH, estradiol, and progesterone compared to the control group. Moreover, levels of superoxide dismutase (SOD) and glutathione peroxidase (GPx) were significantly lower in the RF-EMR group compared to the control. Additionally, there was a notable decrease in the expression of the CREM gene, accompanied by disrupted pituitary/ovarian morphology in the RF-EMR group compared to the control. However, the administration of PG mitigated these changes. The findings of this study indicate that P. ginseng extract shields against pituitary-ovarian impairment linked to RF-EMR exposure from cell phones by boosting antioxidant capacity and promoting the CREM-dependent pathway.

Endocrinological actions of Unkei-to, a herbal medicine, and its clinical usefulness in anovulatory and/or infertile women.

Kampo medicine (Chinese herbal medicine) has been reported to be effective in the treatment of pituitary-ovarian dysfunction in young women and in the treatment of undefined symptoms in perimenopausal women. It has been considered that both the diagnosis and treatment of ovulatory failure in adolescent girls or young women are necessary for the sake of future fertile capacity. However, treatment for the above patients is not easy as steroid hormones and strong stimulators of ovulation should not be recommended because of the several side-effects it causes. Furthermore, young women, especially teenagers, seem to be reluctant to visit gynecology clinics. A number of herbal medicines have been used for many centuries in China and Japan for the treatment of menstrual disorders and infertility. In general, the traditional Chinese herbal prescriptions are rather inexpensive and safe with little side-effects, and have properties for normalizing biological balances. Unkei-to is known to stimulate the synthesis and release of gonadotropins in the rat pituitary. In humans, Unkei-to is known to be effective in various menstrual disorders, abnormal uterine bleeding, and infertility. In the treatment of ovulatory failure, recent dynamic studies have revealed the mechanism by which Unkei-to stimulates the diencephalon-pituitary-ovarian axis in humans. In this paper, we critically review the clinical data available (to date) in order to assess the efficacy of Unkei-to in inducing ovulation in several types of ovulatory disturbances. (Reprod Med Biol 2003; 2: 45-61).

Endometriosis and infertility: The debate continues

A causal relationship between minor endometriosis and infertility or subfertility has not yet been demonstrated, although a significant association is shown by prevalence studies. This article critically reviews the evidence for pituitary-ovarian dysfunction as a cause for subfertility in women with minor endometriosis. The lack of fertile controls with endometriosis presents a methodological problem. Group comparison in studies using tubal infertility cases as controls has demonstrated impaired follicular growth, reduced circulating oestradiol concentrations during the preovulatory phase and oestradiol and progesterone during the early luteal phase, and disturbed luteinizing hormone (LH) surge patterns. LH concentration in preovulatory follicular fluid is also reduced, and granulosa cells collected at the same time have impaired steroidogenic capacity in vitro. However, these findings are not consistent in published studies. Significantly lower oocyte fertilization rates (49%) are found compared with controls (69%), even after maximum stimulation with exogenous follicle-stimulating hormone and human chorionic gonadotrophin (52% versus 69%). The implantation rate is also lower (11% versus 13%). An inherent disorder of follicular function seems likely, and LH surge impairment is probably a secondary effect. Impairment of oocyte fertilization would thus contribute substantially to the natural subfertility associated with endometriosis, but in vitro fertilization is still successful as excess numbers of oocytes are available.

Fertility diminution in female rats with experimental chronic nephrosis.

Chronic aminonucleoside nephrosis in rats is an experimental analogue of human focal segmental glomerulosclerosis. This study was undertaken to define the effects of chronic nephrosis on the pituitary-ovarian axis and on fertility. Chronic nephrosis was induced by puromycin aminonucleoside and followed for 112 days. The estrous cycle was evaluated daily in all rats, whereas biochemical parameters, hormonal concentrations, and fertility were measured on Days 7, 14, 28, 56, 84, and 112 (n = 8). Animals were divided in four experimental groups: A, B, C, and D. Group A was used to determine LH, FSH, progesterone, and estradiol concentrations. Group B was used to evaluate fertility, and groups C and D were added to clarify the role of male rats in the fertility of nephrotic female rats. The results showed a persistent proteinuria in nephrotic rats; the estrous cycle of nephrotic animals was disrupted. The LH and estradiol concentrations were significantly low at all time points evaluated, whereas no significant changes were noted in FSH or progesterone values. In addition, fertility and litter size were diminished in nephrotic female rats. Interestingly, the presence of a male rat or its urine resulted in a positive influence on serum estradiol concentrations of nephrotic female rats. These data indicate that experimental chronic nephrosis results in a pituitary-ovarian dysfunction that is characterized by low LH concentration, hypoestrogenism, failure of the hormonal feedback control, and diminution of fertility. In addition, they show the positive effect of a male rat on the fertility of a nephrotic female, which strongly suggests the participation of pheromones.

Pituitary-ovarian dysfunction and endometriosis.

Significant association between endometriosis, including minor endometriosis, and infertility (or strictly subfertility) is shown by prevalence studies, but a causal relationship has not been established. This review focuses on evidence for pituitary-ovarian dysfunction as a cause for the subfertility. A methodological problem is lack of fertile controls with endometriosis. Group comparison with tubal infertility cases as controls have demonstrated: impaired follicular growth, reduction in circulating oestradiol concentrations during the pre-ovulatory phase and of oestradiol and progesterone during the early luteal phase, and disturbed luteinizing hormone (LH) surge patterns. Reduction in LH concentrations in pre-ovulatory follicular fluid has also been found, and granulosa cells collected at the same time have demonstrated impaired steroidogenic capacity in vitro, but these were not consistently proven findings. Pooled data from published studies show significantly reduced oocyte fertilization rates (49%) compared with controls (69%), even after maximal stimulation with exogenous follicle stimulating hormone (FSH) and human chorionic gonadotrophin (HCG) (54 versus 69%). The implantation rate is also slightly (though significantly) reduced (11 versus 13%). The findings suggest an inherent disorder of follicular function, with LH surge impairment probably being a secondary phenomenon. The resulting reduction in the chance of fertilization of the oocyte would contribute substantially to the subfertility associated with endometriosis. It seems that the benefit of in-vitro fertilization is gained through the excessive number of oocytes obtained by stimulation.

Effect of progestogen therapy on follicular development, related hormone concentrations and fertilization in vitro in unstimulated cycles and unexplained and endometriosis-associated infertility.

Evidence of pituitary-ovarian dysfunction in unexplained and endometriosis-associated infertility has been reported previously. Hormone-suppressive therapy is often used in an attempt to improve fertility, although benefits have not been proven. Our study examines the effect of progestogen (medroxyprogesterone acetate) treatment on women with endometriosis-associated and unexplained infertility, compared with women with tubal damage as functional controls. Pre-ovulatory follicular size and serum and follicular fluid hormone concentrations were measured, and oocyte collection and in-vitro fertilization were attempted, in natural cycles totally unperturbed by exogenous gonadotrophins, for two cycles before and two cycles following treatment with medroxyprogesterone acetate for 2 months. In the endometriosis and unexplained infertility groups, compared with the tubal group, the treatment led to significant reductions in the integrated luteinizing hormone (LH) values (483 versus 664, 559 versus 762 and 864 versus 820 notional IU/l respectively). There were no changes in serum oestradiol or follicular fluid oestradiol, progesterone, follicle stimulating hormone or LH concentrations after treatment. The results suggest that progestogen therapy has no beneficial effect on the pituitary-ovarian dysfunction which contributes to endometriosis-associated and unexplained infertility.

Pituitary-ovarian dysfunction as a cause for endometriosis-associated and unexplained infertility.

This study examines circulating and follicular hormone concentrations and fertilization of oocytes in cycles totally unperturbed by exogenous gonadotrophins in 10 women (25 cycles) with untreated minimal-mild endometriosis and nine women (23 cycles) with prolonged unexplained infertility compared with 16 women (50 cycles) with tubal damage as functional controls. Endometriosis was associated with a significantly longer follicular phase (median 15, 12, 13 days respectively) and reduced oestrogen secretion (median index area under the curve 3063, 3842, 3805 units respectively) compared with controls. Both endometriosis and unexplained infertility had significantly reduced serum luteinizing hormone (LH) surges [median peak serum (LH) 43, 39, 55 IU/l respectively and median area under the curve 661, 687, 823 units respectively] and reduced LH concentrations in follicular fluid (median 19.6, 10.6, 9.2 IU/l respectively). These findings suggest that infertility associated with minor endometriosis and of apparently unexplained aetiology share a common pathophysiology in impaired LH surge secretion. Whether that represents a primary pituitary disorder or is secondary to a defective ovarian signal is discussed.

Pituitary–ovarian dysfunction in rats with induced nephrotic syndrome

The reproductive hormonal profile was evaluated in female rats with experimental nephrotic syndrome induced with a single subcutaneous dose of puromycin aminonucleoside (PAN). Serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone (P4), testosterone and 17 beta-estradiol (E2) were determined sequentially in control and experimental groups on days 1, 3, 7 and 10 after PAN administration. Prolactin levels were also assessed on day 10. In both groups, vaginal smears were taken daily throughout the study to evaluate cyclic histological changes. At the end of the experiment the histological appearance of the ovaries was evaluated by light microscopy. Nephrotic rats had a rapid loss of the estrous cycle starting on day 4, which set them at diestrus. At the same time the hormonal evaluation indicated a gradual decrease in E2, LH and P4 concentrations, starting from days 3, 7 and 10, respectively. No significant changes were noted in FSH or testosterone values. Besides, on day 10, prolactin concentrations remained unmodified. Even though most hormonal levels were found low on day 10, all values except E2 (undetectable) corresponded to the interval reported for the diestrus phase. Likewise, histological examination of ovarian tissue from nephrotic rats showed a considerable increase in the number of atretic follicles. These findings indicate that female rats with nephrotic syndrome develop an important endocrine dysfunction that probably involves steroidogenic tissues (ovary and/or adrenal gland), and suggest the existence of a hypothalamic-hypophyseal impairment.