GnRH analogues in the treatment of fibroids

1993 ◽  
Vol 2 (3) ◽  
pp. 181-197 ◽  
Author(s):  
Christine P West
Keyword(s):  
Ovarian Function ◽  
Uterine Fibroids ◽  
Reproductive Age ◽  
Women Of Reproductive Age ◽  
Gnrh Analogues ◽  
Luteinizing Hormone Releasing Hormone ◽  
Menstrual Dysfunction ◽  
Releasing Hormone ◽  
Pregnancy Wastage ◽  
Gonadotrophin Releasing Hormone

Uterine fibroids are estimated to affect up to 25% of women of reproductive age and are a common cause of morbidity, being associated with menstrual dysfunction, iron deficiency anaemia, pregnancy wastage and subfertility. Their pathogenesis remains unknown but their association with ovarian function and oestrogen production is undisputed and supported by their occurrence only after puberty and the shrinkage observed after the menopause. This oestrogen dependency has recently been exploited therapeutically through investigation of the use of agents that induce a hypo-oestrogenic state, the gonadotrophin-releasing hormone (GnRH) or luteinizing hormone-releasing hormone (LHRH) analogues.

scholarly journals Specific Aspects of Life Quality Estimation and Ways of Rehabilitation in Women Who Underwent Uterine Surgery

2016 ◽  
Vol 23 (3) ◽  
Author(s):  
H. M. Havrylyuk ◽  
O. M. Makarchuk
Keyword(s):  
Blood Supply ◽  
Ovarian Function ◽  
Internal Iliac Artery ◽  
Life Quality ◽  
Uterine Fibroids ◽  
Reproductive Function ◽  
Reproductive Age ◽  
Women Of Reproductive Age ◽  
Internal Iliac

Recently, it has been noticed a great number of uterine fibroids in women with unrealized reproductive function; moreover, the number of combined forms of hyperplastic processes of the reproductive system in 20-25% of women under 30 years of age and 60% of women over 40 years of age is constantly growing creating a favourable background for cancer. It is also known that women with hyperplastic processes suffer from psycho-emotional disorders both before surgeries and after surgical recovery; many of them are diagnosed with adjustment disorder. As many researches note, the main psychotherapeutic aspects include passive view of life, increased anxiety, tendency to dependent behaviour, rejection of own body, protective behaviour and problems with self-assessment. It should also be noted that a comprehensive study of clinical and laboratory data and subjective criteria of life quality is essential in assessment of the feasibility of hysterectomy in women of reproductive age, even if they do not plan to bear children in the future. The objective of the research was to estimate life quality as well as to improve the system of dispensary observation and rehabilitation of women who underwent uterine surgery.Materials and methods. There was performed a comprehensive examination and surgical treatment of 60 women of reproductive age with uterine fibroid who underwent hysterectomy with preservation of appendages. We used modern high quality endocrinological and instrumental techniques. The assessment of the received data was made immediately after surgery, 6 and 2 months, 3 and 5 years after surgery. Quality of life was studied on the basis of a comprehensive assessment using the modified scale of the Nottingham Health Profile and the study of such important indicators as energy, sleep, emotional reactions, social isolation, physical activity, pain. All statistical analysis was performed using a standard package “Statistica for Windows – 6.0”.Results and discussion. On the basis of anamnestic data of patients we revealed health deterioration with high rates of liver and gastrointestinal tract disorders, metabolic disturbances (obesity, hypertensive disorders, fibrocystic breast disease), metabolic-endocrine changes and surgery. Reproductive health in women with uterine fibroid was characterized by long establishment of regular menstrual cycle, its breach in the period of puberty, inflammatory diseases of the genital organs, benign ovarian tumours and their surgical removal, inadequate reproductive behaviour with absent or delayed implementation of reproductive function and induced abortion. 12 months and especially 5 years after surgery there was noticed a progressive deterioration of the ovarian function, which was reflected as the reduction in their volume due to the reduction in the number and size of follicles, deterioration of blood supply to the ovaries, decreased blood flow in the internal iliac artery basin. It should also be noted the progressive hypestrogenism; in addition, there was a clear correlation with the age of the woman, who underwent surgical operation. Changes in life quality of patients with hyperplastic processes of the uterus were manifested in the postoperative period as follows: a decrease in physical activity (43.33% of cases), increased sexual dysfunction (36.66%), inhibition of mental state, conflict-orientated social behaviour, weakening of role functions and subjective deterioration of health and life quality (51.66% of cases).Conclusions. Thus, surgery on uterine fibroids with total or subtotal hysterectomy contributes to interference in a complex neuroendocrine interaction between hypothalamus, pituitary, ovaries, adrenal cortex, thyroid gland and affects the blood supply, innervation, and lymph efflux in the pelvic floor; therefore, postoperative syndromes are polyglandular and polysystemic. Long-term effects after surgery are accompanied by progressive hypestrogenism, decrease in the ovarian function (the reduction in their volume observed during ultrasound examination), reduction in the number and size of follicles, deterioration of blood supply to the ovaries, low blood supply to the internal iliac artery basin.

Characterization of the gonadotrophin-releasing hormone receptor in αT3-1 pituitary gonadotroph cells

1993 ◽  
Vol 136 (1) ◽  
pp. 51-NP ◽  
Author(s):  
L. Anderson ◽  
G. Milligan ◽  
K. A. Eidne
Keyword(s):  
G Protein ◽  
Inositol Phosphate ◽  
Rank Order ◽  
Second Messenger ◽  
Time Dependent ◽  
Binding Studies ◽  
Gnrh Analogues ◽  
Α Subunit ◽  
Releasing Hormone ◽  
Gonadotrophin Releasing Hormone

ABSTRACT The present study has characterized the gonadotrophin-releasing hormone (GnRH) receptor in immortalized αT3-1 pituitary gonadotroph cells. GnRH and GnRH analogues produced both a dose- and time-dependent increase in total inositol phosphate (IP) accumulation. The rank order of potency of these analogues was the same as that obtained in parallel receptor-binding studies in αT3-1 cells. These responses were abolished following pretreatment with a GnRH antagonist. The use of a specific inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) assay demonstrated a rapid but short-lived rise in Ins(1,4,5)P3 production. Intracellular calcium ([Ca2+]i) was subsequently measured in αT3-1 cells using dual wavelength fluorescence microscopy combined with dynamic video imaging. GnRH produced a biphasic rise in [Ca2+]i. The initial calcium transient was complete within seconds while the smaller secondary plateau phase lasted several minutes. G-protein involvement in the IP response to GnRH in αT3-1 cells was investigated using sodium fluoride (NaF) and pertussis toxin (PTx) which activate and inactivate G-proteins respectively. Like GnRH, NaF produced a dose- and time-dependent increase in IP accumulation. Activation of phospholipase C in these cells by either GnRH or NaF was PTx-insensitive, suggesting that the G-protein involved was neither Gi nor Go but more probably Gq. Immunoblot analysis of αT3-1 cell membranes using antisera raised against the predicted C-terminal decapeptide of the α subunit of Gq demonstrated the presence of Gq in αT3-1 cells. Collectively these results show that the GnRH receptors expressed in αT3-1 cells are coupled to the phosphatidylinositol second messenger pathway via a specific G-protein. αT3-1 therefore represents a convenient model in which to study GnRH-related second messenger pathways. Journal of Endocrinology (1993) 136, 51–58

scholarly journals ESTIMATION TO EFFICIENCY OF THE MULTIFUNCTION METHOD ОF ENDOMETRIOSIS OVARIЕS TREATMENT

2020 ◽  
Vol 73 (5) ◽  
pp. 868-872
Author(s):  
Iryna M. Nikitina ◽  
Volodymyr I. Boiko ◽  
Svitlana A. Smiian ◽  
Tetiana V. Babar ◽  
Natalia V. Kalashnyk ◽  
...  
Keyword(s):  
Gonadotropin Releasing Hormone ◽  
Inhibin B ◽  
Reproductive Age ◽  
Sexual Life ◽  
Control Group ◽  
Women Of Reproductive Age ◽  
Releasing Hormone ◽  
Antral Follicles ◽  
Group I ◽  
Laparoscopic Removal

The aim: The aim of the study was to improve the results of treatment of patients with endometriosis by using a combination method of therapy. Materials and methods: For two years, 136 women of reproductive age who underwent laparoscopic surgeries for ovarian endometriosis were monitored: Group I (n = 24) did not receive any hormonal treatment in the perioperative period; Group II (n = 32) – received gonadotropin-releasing hormone agonists within 3 months after surgery; Group III (n = 80) prior to laparoscopic removal of the ovarian cyst used gonadotropin-releasing hormone agonists – Triptorelin 3.75 mg intramuscularly for 2 months, as well as three months after surgery. The control group consisted of 30 healthy women of reproductive age with regular menstrual periods. All patients underwent transvaginal ultrasound, counting the number of antral follicles before and after treatment. Serum hormone levels (FSH, prolactin, thyrotropic hormone, anti-Mullerian hormone, inhibin B) were determined by enzyme-linked immunosorbent assay on Cobas e-411 analyzer (Roche Diagnostics, Switzerland) on day 2-3 of the menstrual cycle and on day 2–3 of the first menstrual period after the end of treatment. Laparoscopic removal of the cyst was performed with exfoliation of the cyst, hemostasis on the wound surface of the bed of the cyst was performed with a bipolar electrocoagulator. Bipolar coagulation and resection of the ovarian tissue with no potential was used during surgical treatment of the ovaries, which made it possible to preserve the intact portion of the ovary as much as possible. Results: Analysis of ovarian reserve indices, namely number of antral foliculs, number of antral follicles, AMG, and inhibin B levels in all examined patients with ovarian endometriomas were significantly lower than those of the control group before the start of treatment: in the ovarian endometrial group group 1.26 times (p <0.01), inhibin B – 1.5 times (p <0.01), the number of antral follicles – 1.2 times (p <0.01), due to the development dystrophic changes of the follicular apparatus due to prolonged compression, hypoxia, fibrosis in the ovaries. Patients who planned pregnancy were advised to have an active sexual life before menstruation was restored. In 23 (46.9%) of 49 patients who had reproductive plans, pregnancy occurred without first menstruation after a course of gonadotropin-releasing hormone agonists, 12 (24.5%) women became pregnant during the first three menstrual cycles. Extracorporeal fertilization was recommended for women who did not have pregnancy within 6 months of surgery. For two years in women who did not plan pregnancy, recurrence of endometriosis was not observed. Conclusions: The combination of laparoscopic treatment with gonadotropin-releasing hormone agonists in patients with endometriosis with infertility allowed to restore reproductive function in 71.4% of women, which indicates the effectiveness of the treatment method used. In addition, it helps to achieve lasting remission and addresses the socio-social problems of women’s health and maternity.

Pathogenetic mechanisms of endometrial hyperplasia in women of reproductive age

2020 ◽  
Vol 19 (5) ◽  
pp. 44-50
Author(s):  
I.M. Ordiyants ◽  
◽  
A.A. Kuular ◽  
A.A. Yamurzina ◽  
D.S. Novginov ◽  
...  
Keyword(s):  
Estrogen Receptors ◽  
Pyruvate Kinase ◽  
Endometrial Hyperplasia ◽  
Uterine Fibroids ◽  
Uterine Bleeding ◽  
Reproductive Age ◽  
Women Of Reproductive Age ◽  
Pyruvate Kinase M2 ◽  
Pathogenetic Mechanisms ◽  
Group I

Objective. To analyze pathogenetic mechanisms underlying the development of endometrial hyperplasia in women of reproductive age. Patients and methods. We have examined 143 women of reproductive age with endometrial hyperplasia (EH). Study participants were divided into three groups: Group I included EH patients without atypia; Group II included patients with atypical hyperplasia of the endometrium; Group III (control group) comprised 56 women with abnormal uterine bleeding, in whom we excluded adenomyosis, uterine fibroids, endometrial hyperplasia, endometrial cancer, and iatrogenic causes of uterine bleeding. Genomic DNA was isolated using phenol-chloroform extraction. Real-time polymerase chain reaction (RT-PCR) was used to detect microRNA-210, -18a, -221, and -222. The detection of tumor pyruvate kinase M2 was performed using the ScheBo® Tumor M2-PK kit designed for quantitative assessment of this metabolic cancer marker in plasma and endometrial tissue samples. Results. Significant risk factors triggering the pathogenetic mechanism of EH development in reproductive age include extragenital disorders (obesity, thyroid diseases, diseases of the urinary system, hypertension) and gynecological diseases (pelvic inflammatory diseases, adenomyosis, benign breast dysplasia, uterine fibroids). Alterations affecting estrogen receptors lead to changes in microRNA messengers, which, in turn, affect target genes and cause changes in the adaptive abilities of the cell. Expression of pyruvate kinase M2 in this chain confirms proapoptotic changes in the cell and the risk of its atypia. Conclusion. The pathogenesis of EH is based on the following factors: polymorphism of the ERS1 and PRG genes, increased expression of miRNA-210, -18a, and -222, decreased expression of miRNA-221, and overexpression of pyruvate kinase M2. Key words: endometrial hyperplasia, miRNA, pyruvate kinase M2, progesterone receptors, estrogen receptors

Infertility

2013 ◽  
pp. 551-566
Author(s):  
John Reynard ◽  
Simon Brewster ◽  
Suzanne Biers
Keyword(s):  
Luteinizing Hormone ◽  
Male Infertility ◽  
Anterior Pituitary ◽  
Treatment Options ◽  
Follicle Stimulating Hormone ◽  
Reproductive Physiology ◽  
Seminiferous Tubules ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Gonadotrophin Releasing Hormone

Male reproductive physiology 552 Aetiology and evaluation of male infertility 554 Investigation of male infertility 556 Oligozoospermia and azoospermia 560 Varicocele 562 Treatment options for male infertility 564 The hypothalamus secretes luteinizing hormone-releasing hormone (LHRH), also known as gonadotrophin-releasing hormone (GnRH). This causes the pulsatile release of anterior pituitary gonadotrophins called follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which act on the testis. FSH stimulates the seminiferous tubules to secrete inhibin and produce sperm; LH acts on Leydig cells to produce testosterone (...

Uterine artery embolization in uterine fibroids patients of reproductive age and its role in shaping of autoimmune oophoritis

2016 ◽  
Vol 3 (2) ◽  
pp. 81-87
Author(s):  
Elena A. Sosnova
Keyword(s):  
Uterine Artery Embolization ◽  
Uterine Artery ◽  
Ovarian Function ◽  
Clinical Laboratory ◽  
Uterine Fibroids ◽  
Treatment Method ◽  
Reproductive Age ◽  
Long Term Results ◽  
Artery Embolization ◽  
Premature Failure

In women of the reproductive age who have preserved the uterus after uterine artery embolization (UAE) and are interested in restoring fertility, the clinical evaluation of long-term results of this treatment method was executed with the use both of a questionnaire survey (n = 98), and determination of the status of ovarian reserve, ovaries, thyroid gland(n = 52). Performed retro- and prospective clinical-laboratory and instrumental methods of the investigation allowed to reveal a higher risk of the development of remote complications of UAE, in particular in the premature failure of ovarian function.

scholarly journals Tactics for minimizing risk of increasing estradiol against the background of aromatase inhibitors in combination with gonadotropin releasing hormone agonists in adjuvant therapy for breast cancer in premenopausal patients. Pilot study results

2018 ◽  
pp. 76-84
Author(s):  
I. B. Kononenko ◽  
A. V. Snegovoi ◽  
L. V. Manzyuk ◽  
E. I. Kovalenko ◽  
V. Yu. Selchuk
Keyword(s):  
Breast Cancer ◽  
Menstrual Cycle ◽  
Adjuvant Therapy ◽  
Aromatase Inhibitors ◽  
Ovarian Function ◽  
Reproductive Hormones ◽  
Gonadotropin Releasing Hormone ◽  
Gnrh Analogues ◽  
Releasing Hormone ◽  
Premenopausal Patients

Aromatase inhibitor (AI) combined with Gonadotropin-releasing hormone agonist (GnRH-a) have been recognized as an effective approach to adjuvant endocrinotherapy for breast cancer (BC) in premenopausal patients with adverse predictive factors. However, the risk of non-optimal suppression of the ovaries due to the mechanism of action of aromatase inhibitors has been proven. Recently published SOFT-EST studies showed that the blood estradiol (E2) level in 37% of patients was above the level that was permissible for the purpose of this group of drugs. And although today there is no enough scientific justification to interpret this result, the introduction of aromatase inhibitors in adjuvant therapy in young women requires the search for tactics to reduce the risk of mediated increase in estradiol against the background of such therapy. Alertness occurs when the E2 serum level exceeds the menopause limit by the time the aromatase inhibitors are prescribed. Objective of the study. Determine the tactics for minimizing the risk of increasing estradiol against the background of aromatase inhibitors in combination with GnRH-a in adjuvant therapy for breast cancer in premenopausal patients. Material and methods. 47 patients of ≤ 50 years old with GR + HER2- Stages I-III Breast Cancer and a regular menstrual cycle before the start of neo-/adjuvant chemotherapy were studied. E2 and FSH levels were assessed at the stage prior to chemotherapy and immediately prior to administering adjuvant endocrinotherapy. After the completion of chemotherapy, only 7 out of 47 women had the menstrual cycle - patients without clinical and biochemical suppression of ovarian function (SOF). 86% of cases had cytostatic amenorrhea (n = 40), of which 23 cases (58%) showed that this condition was not combined with the biochemical response of sex hormones, i.e. there was no biochemical SOF. Thus, the study group included 30 patients, who were supposed to be treated with aromatase inhibitors + GnRH analogues, and had no clinical or biochemical menopause by the time adjuvant endocrinotherapy was prescribed. In order to reduce the risk of mediated increase in estradiol, even with pharmaceutical “switching off” ovarian function, the patients were prescribed the GnRH analogue (Buserelin Depot) before starting aromatase inhibitors therapy. Results and conclusion. A progressive decrease in E2 level was determined after each subsequent administration of Buserelin Depot. The median values remained low only after the third injection. Following the chemotherapy, a decrease in estradiol was accompanied by a physiological increase in the FSH levels in 73% of women. The administration of Buserelin Depot led to a significant decrease in FSH median (p <0.01) in 90% of patients. Aromatase inhibitors and continuing GnRH-a were prescribed to 97% of patients. The results indicate that the achievement of ovarian function suppression prior to the administration of IA, can be considered as a reliable tactics for adjuvant endocrinotherapy in patients of reproductive age. The dynamic assessment of reproductive hormones (E2, FSH) is recognized useful when choosing or correcting therapy in such patients.

scholarly journals Understanding the Impact of Uterine Fibroids on Human Endometrium Function

2021 ◽  
Vol 9 ◽  
Author(s):  
Antonia Navarro ◽  
Maria Victoria Bariani ◽  
Qiwei Yang ◽  
Ayman Al-Hendy
Keyword(s):  
Transforming Growth Factor ◽  
Vascular System ◽  
Uterine Fibroids ◽  
Transforming Growth Factor Β ◽  
Uterine Wall ◽  
Reproductive Age ◽  
Menstrual Bleeding ◽  
Women Of Reproductive Age ◽  
Myometrial Cells ◽  
The Impact

Uterine fibroids (leiomyomas) are the most common benign gynecological tumors in women of reproductive age worldwide. They cause heavy menstrual bleeding, usually leading to severe anemia, pelvic pain/pressure, infertility, and other debilitating morbidities. Fibroids are believed to be monoclonal tumors arising from the myometrium, and recent studies have demonstrated that fibroids actively influence the endometrium globally. Studies suggest a direct relationship between the number of fibroids removed and fertility problems. In this review, our objective was to provide a complete overview of the origin of uterine fibroids and the molecular pathways and processes implicated in their development and growth, which can directly affect the function of a healthy endometrium. One of the most common characteristics of fibroids is the excessive production of extracellular matrix (ECM) components, which contributes to the stiffness and expansion of fibroids. ECM may serve as a reservoir of profibrotic growth factors such as the transforming growth factor β (TGF-β) and a modulator of their availability and actions. Fibroids also elicit mechanotransduction changes that result in decreased uterine wall contractility and increased myometrium rigidity, which affect normal biological uterine functions such as menstrual bleeding, receptivity, and implantation. Changes in the microRNA (miRNA) expression in fibroids and myometrial cells appear to modulate the TGF-β pathways and the expression of regulators of ECM production. Taken together, these findings demonstrate an interaction among the ECM components, TGF-β family signaling, miRNAs, and the endometrial vascular system. Targeting these components will be fundamental to developing novel pharmacotherapies that not only treat uterine fibroids but also restore normal endometrial function.

Comparison of indicators quality of life in women after operative rehabilitation on uterine fibroids

2016 ◽  
pp. 94-97
Author(s):  
O. Makarchuk ◽  
◽  
G. Gavrilyuk ◽  
Keyword(s):  
Quality Of Life ◽  
Short Form ◽  
Uterine Fibroids ◽  
The Body ◽  
Reproductive Age ◽  
Control Group ◽  
Psychosomatic Disorders ◽  
Women Of Reproductive Age ◽  
Surgical Recovery

One of the most common benign hyperproliferative diseases of the female reproductive organs are uterine leiomyoma, the frequency of which, according to various literature in women of reproductive age is between 20% and 40%, and is the main indication for surgery, including removal of the organ. Long-term effects of surgical interventions for uterine fibroids have been the subject of numerous debates. In modern literature is not much research on the assessment of the quality of life both in organ treatment of uterine fibroids, and after surgical recovery. Quality of life have undoubtedly significant prognostic value and can be used in selecting the optimal treatment of uterine fibroids, as well as the development of individual approach to postoperative rehabilitation of patients. The objective: was the study of quality of life and the search for possible ways to improve in women after surgical healing uterine fibroids. Materials and methods. A survey of 80 women of reproductive age (study group), which was conducted without hysterectomy applications. Clinical and laboratory examination conducted in the dynamics of the postoperative period and at 6, 12 months and 3 years after surgical recovery. Assessment of comparative analysis require further formation of two groups comparing 20 patients with myoectomy and 20 women with no uterus amputation supravaginal applications. The control group consisted of 20 healthy patients. Assessment of quality of life survey conducted by using common clinical trials and monitoring at the individual questionnaire MOS 36- Item Short-Form Health Survey- MOS SF-36. Statistical analysis of the survey results was carried out using the software package Microsoft Office Excel and Statistica 6.0 for Windows. Results. In women, the main indicators of psycho-emotional and vegetative manifestations were most pronounced immediately after surgery and remained stable in three years with no significant deviations in the comparison group. Among the most frequently observed fatigue (76.25%), sleep disorders (88.75%), irritability and mood changes (76.25%) and emotional lability, anxiety and depressive symptoms. Of The results of evaluation of quality of life should be noted that first disturbed functioning role of women because of poor physical and emotional state, as evidenced by the significant differences obtained on the scale of General Health (GH) (overall health). Three years after the rapid improvement in women’s core group established stable condition posthisterektomy pronounced effect on quality of life. Thus, in total 33.75% of the principal groups characterized as low quality of life, compared with 5.0% of patients in the control group and 10,0% of women with myoectomy. Conclusions. The highest level of dissatisfaction with life studied patients presenting in health – 28.75% (23) cases, slightly less professional – 22.5% (18), emotional – 17.5% (17) and as in the sexual sphere – 13.75% (11) cases. That associated complications related symptoms posthisterektomy syndrome, increases the level of stress and hysterectomy as the body creates prerequisites for psychosomatic disorders. This action provides additional risk factors for the development of psychosocial distress in this group of patients. Key words: uterine fibroids, hysterectomy, posthisterektomy syndrome, psychosomatic disorders, quality of life.

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