Medical Oophorectomy Research Articles

Leiomioma Metastásico Benigno Pulmonar

Benign metastatic leiomyomatosis (BML) is a neoplastic smooth muscle disease where the lung is the most affected organ. So, we will detail the literature by presenting the following case of a patient who underwent surgical treatment at the pulmonary level resection of the lung lesion with subsequent pathologic confirmation by biopsy. The clinical presentation of benign metastatic leiomyomatosis can range from asymptomatic onset to rapid progression that leads to respiratory failure and death. The patient presented with pulmonary symptoms such as cough, dyspnea, or chest tightness, with a diagnostic image of a simple and contrasted thoracic CT scan showing pleural effusion. A surgical procedure was performed by thoracoscopy with evidence of a tumor-like lesion with a cystic component. Pleurectomy with decortication was performed, and it was decided to perform a non-anatomic segmental pulmonary lobectomy. The pathological anatomy revealed benign leiomyomas without atypia and mitotic activity. The patient has not yet taken a standard treatment for benign metastatic leiomyomatosis due to the hormone-sensitive characteristics of the BML and is currently in multidisciplinary follow-up. Treatments are based on hormonal manipulation along with surgical or medical oophorectomy.

Quality of Life Outcomes in a Cohort of Women Undergoing Surgical Oophorectomy for the Treatment of Medical Oophorectomy-Responsive Chronic Pelvic Pain

Objective: To determine the long-term post-operative impact of surgical oophorectomy on pain severity and quality of life (QOL) in women with chronic pelvic pain (CPP) responsive to pre-operative medical oophorectomy.

NOT ALL THAT METASTASIZES IS CANCER: A CASE OF BENIGN METASTASIZING LEIOMYOMA

SESSION TITLE: Lung Pathology 1 SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Benign metastasizing leiomyoma(BML) is a rare tumor primarily affecting the lungs of late reproductive-aged women with a history of uterine leiomyomas.It has benign histological features, though it metastasizes (biological behavior of malignancy). Immunostains are helpful in diagnosis.They are usually asymptomatic and an incidental finding.A hysterectomy is needed to rule out low grade uterine sarcoma. CASE PRESENTATION: 46F presented with a 2-week history of exertional dyspnea and pleuritic pain. Patient also complained of fatigue. She denied cough, wheezing, constitutional symptoms, leg swelling or orthopnea. Other review of system is nil of significance.Past history includes chronic back pain, incidental lung nodules noted on CT scan following an MVA, and previous tobacco use of <5 pack years and no occupational exposuresPhysical examination revealed a healthy looking female with stable vital signs and otherwise unremarkable examination.CT chest revealed multiple nodules with largest ones in the LUL (2.5cm), RML (2.3cm) and RUL 1.4(cm), compared to prior study nodules had increased in size and number.Prior evaluation of nodules with a CT-guided biopsy was reported as fibrogranulomatous process. Autoimmune workup was negative. Electromagnetic navigation bronchoscopy for biopsy was done revealing reactive appearing bronchial cells and pulmonary macrophages, few crowded cellular groups and no malignant cells. Cultures were negative.PET scan demonstrated nodules with SUV 1.4-1.8 without any abnormal extrathoracic uptake.Surgical lung biopsy was done with wedge resection of left upper lobe. Histology showed cystic, bland-appearing spindle cell neoplasm which was positive for both epithelial (TTF-1 and keratin) and smooth muscle tissue (Desmin and SMA). Cells stained positive for ER/PR, consistent with gynecologic origin leading to diagnosis of leiomyoma.Patient underwent hysterectomy and bilateral salpingoophorectomy showing adenomyosis and intramural leiomyomas. DISCUSSION: Bilateral pulmonary nodules in a late reproductive female can either be benign or malignant. Nodules larger than 1 cm suggest metastatic disease but the chronicity and slow doubling time in this case made malignancy less likely. Benign etiology was favored including granulomatous infection and connective tissue disease, however work up was inconclusive. Results from surgical biopsy was ambiguous given the staining for both smooth muscle and epithelial markers.Lesions vary in size, with smooth well-defined margins and diffuse nonspecific distribution. They are believed to be hematogenous metastases from morphologically benign uterine tumors. With ER/PR positivity in lung lesions, there is the option to treat with hormonal manipulation through surgical or medical oophorectomy. CONCLUSIONS: BML should be a differential diagnosis in females with pulmonary nodules and a history of uterine leiomyoma. Reference #1: Goyle et al; Benign metastasizing leiomyomatosis: case report and review. Am J Clin Oncol. 2003 Oct;26(5):473-6. Reference #2: Eun Young Ki et al; Benign metastasizing leiomyoma of the lung. World J Surg Oncol. 2013; 11: 279. DISCLOSURES: No relevant relationships by Arthur Oliver Romero, source=Web Response No relevant relationships by Cordelia Solomon, source=Web Response

Medical ovariectomy in menopausal breast cancer patients with high testosterone levels: a further step toward tailored therapy.

Five years of adjuvant therapy with anti-estrogens reduce the incidence of disease progression by about 50% in estrogen receptor-positive breast cancer patients, but late relapse can still occur after anti-estrogens have been discontinued. In these patients, excessive androgen production may account for renewed excessive estrogen formation and increased risks of late relapse. In the 50% of patients who do not benefit with anti-estrogens, the effect of therapy is limited by de novo or acquired resistance to treatment. Androgen receptor and epidermal growth factor receptor overexpression are recognized mechanisms of endocrine resistance suggesting the involvement of androgens as activators of the androgen receptor pathway and as stimulators of epidermal growth factor synthesis and function. Data from a series of prospective studies on operable breast cancer patients, showing high serum testosterone levels are associated to increased risk of recurrence, provide further support to a role for androgens in breast cancer progression. According to the above reported evidence, we proposed to counteract excessive androgen production in the adjuvant setting of estrogen receptor-positive patients and suggested selecting postmenopausal patients with elevated levels of serum testosterone, marker of ovarian hyperandrogenemia, for adjuvant treatment with a gonadotropins-releasing hormone analogue (medical oophorectomy) in addition to standard therapy with anti-estrogens. The proposed approach provides an attempt of personalized medicine that needs to be further investigated in clinical trials.

Benign metastasizing leiomyoma of the lung

Benign leiomyomas of the uterus are uncommonly found in association with benign smooth muscle tumors beyond the confines of the uterus. Benign metastasizing leiomyoma (BML) is a rare disease in which the lung is described to be the most afflicted extrauterine organ. We present a brief review of the literature, along with case reports for four patients who were followed up after resection of a pulmonary lesion or after pathological confirmation by biopsy. The clinical course of BML varies from chronic asymptomatic appearance to rapid progression, leading to respiratory failure and death. Our BML patients did not complain of pulmonary symptoms, such as cough, dyspnea, or chest tightness. Pathology revealed benign leiomyomas with no atypia and mitotic activity <5 per 10 high-power field. Immunohistochemical staining was positive for actin and desmin. A standard treatment for BML has not yet been established. Because of the hormone-sensitive characteristics of BML, treatments are based on hormonal manipulation along with either surgical or medical oophorectomy. Benign metastasizing leiomyoma can be observed in postmenopausal women. We observed four patients who did not receive adjuvant hormonal therapy because they were postmenopausal or perimenopausal. All patients are still healthy and show no evidence of recurrence or progression of the disease.

Gonadotropin releasing hormone agonists: Expanding vistas

Gonadotropin-releasing hormone (GnRH) agonists are derived from native GnRH by amino acid substitution which yields the agonist resistant to degradation and increases its half-life. The hypogonadotropic hypogonadal state produced by GnRH agonists has been often dubbed as “pseudomenopause” or “medical oophorectomy,” which are both misnomers. GnRH analogues (GnRH-a) work by temporarily “switching off” the ovaries. Ovaries can be “switched off” for the therapy and therapeutic trial of many conditions which include but are not limited to subfertility, endometriosis, adenomyosis, uterine leiomyomas, precocious puberty, premenstrual dysphoric disorder, chronic pelvic pain, or the prevention of menstrual bleeding in special clinical situations. Rapidly expanding vistas of usage of GnRH agonists encompass use in sex reassignment of male to female transsexuals, management of final height in cases of congenital adrenal hyperplasia, and preserving ovarian function in women undergoing cytotoxic chemotherapy. Hypogonadic side effects caused by the use of GnRH agonists can be tackled with use of “add-back” therapy. Goserelin, leuprolide, and nafarelin are commonly used in clinical practice. GnRH-a have provided us a powerful therapeutic approach to the treatment of numerous conditions in reproductive medicine. Recent synthesis of GnRH antagonists with a better tolerability profile may open new avenues for both research and clinical applications. All stakeholders who are partners in women's healthcare need to join hands to spread awareness so that these drugs can be used to realize their full potential.

Aromatase inhibitors prevent the estrogen rise associated with the flare effect of gonadotropins in patients treated with GnRH agonists

This was a preliminary study to determine the effect of aromatase inhibitors in preventing the flare induced by GnRH agonist (GnRH-a) in women with endometriosis (n = 9) or leiomyomata (n = 4) who were given letrozole on the first 5 days of the GnRH-a therapy. Serum LH and FSH levels showed the typical flare 1 day after the injection of the GnRH-a; however, E(2) declined immediately after letrozole administration and was notably suppressed at 1, 2, and 4 days after GnRH-a. No patients complained of clinical symptoms typical of the GnRH-a flare phenomenon.

Symptoms of Premenstrual Syndrome and Their Association With Migraine Headache

To determine the association between the severity of premenstrual (PMS) symptoms and headache outcome measures during natural menstrual cycles and after medical oophorectomy. Premenstrual syndrome may occur in 64% of those with pure menstrual migraine and 33% of those with menstrually related migraine. Few past studies have examined the relationship between the severity of PMS symptoms and migraine headache. Data were obtained from a 6.5-month randomized-controlled trial examining the role of medical oophorectomy in the prevention of migraine headache and later divided into two data sets for analysis purposes. The menstrual cycle data set was composed of data from three natural menstrual cycles obtained from 21 participants during lead-in and placebo run-in phases. Each menstrual cycle was subdivided into seven 3-day intervals based on urine hormone metabolites. The medical oophorectomy data set included data from a 2-month treatment period in which a medical oophorectomy was induced by gonadotropin-releasing hormone agonists (GnRHa) and participants were randomized to transdermal estradiol or a matching placebo (GnRHa/estradiol and GnRHa/placebo groups, respectively). All participants completed a daily diary recording the severity of PMS symptoms and headache outcome measures. The primary outcome measures were the PMS index (mean of the daily PMS severity scores) and the headache index (mean of the headache severity scores). Pearson correlation coefficients were used to assess the degree of association between the outcome measures. Menstrual Cycle Data Set.-The PMS index was significantly correlated with the headache index during native menstrual cycles (correlation coefficient of 0.47; P < .05) and during all seven intervals of the menstrual cycle (correlation coefficients of 0.39 to 0.65; all P values < .05). Medical Oophorectomy Data Set.-Correlation coefficients between the PMS and headache indices were 0.58 and 0.47 for the GnRHa/estradiol (n = 9) and GnRHa/placebo groups, respectively (P-values of <.05). Moderate correlations exist within female migraineurs between the severity of PMS symptoms and headache outcome measures throughout natural menstrual cycles as well as after medical oophorectomy. Our data would suggest that the presence and severity of headache might modulate PMS symptoms in female migraineurs.

Nonstandard and adjunctive medical therapies for systemic lupus erythematosus

Nonstandard and adjunctive medical therapies for systemic lupus erythematosus

Reduction in bone formation and elevated bone resorption in ovariectomized rats with special reference to acute inflammation

Changes in bone modeling and remodeling in the tibia of growing rats within 30 days of ovariectomy (ovx) were evaluated by histomorphometric, mechanical, and biochemical means. Three days after ovx, suppressed bone formation was seen. This was shown by reduced osteoid volume, osteoblast surface, and bone formation rate in the secondary spongiosa, and a reduced longitudinal growth rate in the growth plate. In addition, the alkaline phosphatase and tartrate-resistant acid phosphatase activity in bone marrow supernatants was suppressed in conjunction with elevated serum sialic acid levels, indicating inflammation. Although estrogen deprivation itself may provoke the inflammatory process, the serum sialic acid level in the ovx group returned to the baseline level within 5 days after surgery, while that of estradiol in the ovx group remained consistently lower. This suggests that surgical stress, not estrogen deprivation, is the primary cause of the inflammatory response shortly after ovx. A significant difference ( p < 0.01) between the ovx and sham rats was seen in the osteoclast surface, which peaked on day 7 in the ovx rats. On day 14 postovariectomy, the bone formation rate peaked and remained constant until day 30. In the ovx rats, there was a sustained reduction in the serum albumin level until day 30. Estrogen deprivation may be the primary cause of these changes, because both surgical ovx and medical oophorectomy with gonadotropin-releasing hormone agonist (GnRHa) reduce the serum albumin level. In numerous studies dealing with changes after ovx in rats, we have observed: 1) a transient reduction in bone formation in relation to inflammatory changes evoked by ovx surgery, and 2) a sustained reduction in the serum albumin level for at least 30 days after ovx that is possibly due to estrogen deprivation.

Regression of uterine low-grade smooth-muscle tumors metastatic to the lung after oophorectomy

Metastatic uterine low-grade smooth-muscle tumors may present with pulmonary symptoms and radiographic lung abnormalities consistent with metastatic neoplasms. Ovarian hormone stimulation of these smooth-muscle tumors has been suggested, but the role of surgical or medical oophorectomy has not been established in patients with metastatic disease. Two women with histologically confirmed uterine low-grade smooth-muscle tumors metastatic to the lung had progressive and complete tumor regression after oophorectomy and no further therapy. Some uterine low-grade smooth-muscle tumors metastatic to the lung regress after oophorectomy. Removing ovarian hormone stimulation may result in complete tumor regression without the need for further therapy.

Hormonal Treatment of Advanced Breast Cancer

Endocrine therapy for breast cancer has been used for almost a century, but because of the enormous success of tamoxifen there has been a resurgence of interest by the pharmaceutical industry to develop new and innovative endocrine therapies. Overall, the strategy is quite simple. Estrogen stimulates growth; therefore, the goal is to deny the breast tumor estrogens. Tamoxifen accomplishes this by blocking the estrogen receptor. The new antiestrogens, toremifene and droloxifene, however, appear to have no greater activity than tamoxifen in the treatment of advanced disease and therefore may ultimately offer no advantages over current therapy. In contrast, the pure antiestrogens hold additional promise as they may produce a more profound inhibitory effect on the tumor, and the response may be maintained longer. An orally active, pure antiestrogen, however, would be an important advance. The strategy of using GnRH agonists for premenopausal patients clearly has merit to produce a chemical oophorectomy. The strategy could be integrated into the general treatment plan for the young premenopausal patient taking tamoxifen who may not have had her menstrual cycles stopped by combination chemotherapy. The GnRH agonists would block the reflex rise in estradiol caused by tamoxifen therapy and ultimately produce a more efficient antihormonal therapy. Indeed, the different specific aromatase inhibitors can also be integrated into the treatment plan to produce a complete estrogen blockade. Whether the use will be found to be superior to pure antiestrogens, however, must await the completion of comparative clinical studies. If all the results of endocrine therapy are therapeutically similar, the final strategy may depend on the acceptability by the patient of an individual delivery method for each pharmaceutical approach.

Effects of medical oophorectomy and hormone replacement on mood, sexual interest, cognition. And cerebral blood flow

Effects of medical oophorectomy and hormone replacement on mood, sexual interest, cognition. And cerebral blood flow

Endometriosis. Diagnostic clues and new treatment options.

Endometriosis results in significant pelvic pain, dysmenorrhea, and infertility. Recognition of the signs and symptoms of endometriosis can result in early diagnosis and treatment. Management includes surgical intervention to debulk large lesions and pharmacologic therapy to produce a medical oophorectomy. Primary care physicians should suspect endometriosis in infertile patients with pelvic pain.

A potential primate model for bone loss resulting from medical oophorectomy of menopause : J. Clin. Endocrinol. Metab. 1990 71/1 (105–110)

A potential primate model for bone loss resulting from medical oophorectomy of menopause : J. Clin. Endocrinol. Metab. 1990 71/1 (105–110)

Hormonal and biochemical changes during treatment of endometriosis with the luteinizing hormone-releasing hormone (LH-RH) agonist [formula omitted]LH-RH ethylamide

The effect of medical oophorectomy induced by treatment with the luteinizing hormone-releasing hormone (LH-RH) agonist [D-Trp6,des-Gly-NH2(10)]LH-RH ethylamide was studied in 34 patients with laparoscopically proven endometriosis. Tamoxifen was administered during the 1st month of therapy to prevent flare-up of the disease during the estrogen surge. Fifteen women had a decrease of their laparoscopy scores translated into an improvement in the stage of disease, whereas in 12 others, the decrease in their scores was not enough to allow a change of disease stage. The 2nd laparoscopy was not performed in 7 women. Medical oophorectomy, after daily injection of the LH-RH agonist (LH-RH-a), was accompanied by low levels of circulating estradiol. The serum concentration of all delta 4-3-ketosteroids was significantly decreased during medical oophorectomy, whereas the level of circulating delta 5-3 beta-hydroxysteroids was not altered except for pregnenolone. The present data indicate that medical oophorectomy induced by an LH-RH-a in association with tamoxifen is a very efficient and well tolerated therapy in endometriosis.

A Potential Primate Model for Bone Loss Resulting from Medical Oophorectomy or Menopause*

This study examined the potential use of the GnRH agonist-treated female monkey as a model for bone loss after medical oophorectomy or the onset of menopause in women. Three female rhesus monkeys (13-16 yr of age) were treated continuously for 10 months with 25 micrograms/day GnRH agonist using osmotic minipumps. All three animals exhibited normal menstrual cycles before treatment. Within 5 weeks of the beginning of GnRH agonist treatment, serum progesterone and estradiol concentrations had fallen to low values and did not rise significantly during the remaining treatment period. The decline in ovarian steroidogenesis was correlated with a reduction in bone mineral density (BMD; bone mineral content/bone width) of the caudal vertebrae and humerus. The reduction of BMD of the caudal vertebrae occurred gradually. The downward trend was evident during the first 3 treatment months, but did not fall significantly below pretreatment levels until 9 months of GnRN agonist treatment. The overall decline in BMD for the caudal vertebrae was approximately 14% after 9 months of GnRH agonist treatment. The measured decline in BMD of the humorous was 11%. Serum osteocalcin levels rose more than 10-fold above pretreatment values between 4 and 7 months of GnRH agonist treatment before declining to levels that approached pretreatment concentrations between 8 and 10 months of treatment. Menstrual cycles were reinitiated within 4 weeks after the termination of treatment, as shown by luteal phase increases in serum progesterone concentrations. BMD of the humerus and caudal vertebrae remained subnormal 2 months posttreatment, but by 5 months had recovered to near-pretreatment values. These data suggest that ovarian hormone deprivation induced by GnRH agonist administration is associated with a decline in BMD in female monkeys, and that this animal model may be an excellent model for postmenopausal bone loss or bone reduction resulting from medical oophorectomy. The GnRH agonist-treated monkey also has the potential to be developed as a model for type I postmenopausal osteoporosis.

Response to endocrine manipulation and oestrogen receptor concentration in large operable primary breast cancer

Forty-three patients with large (greater than or equal to 4 cm) but operable carcinoma of the breast have been treated by endocrine manipulation before definitive local surgery. This has allowed the study of the relationship between response to therapy and pretreatment oestrogen receptor (ER) concentration, as measured by a dextran-coated charcoal adsorption method. Premenopausal patients (17) were treated by surgical (4) or medical (13) oophorectomy. Post-menopausal patients (26) received either tamoxifen (10) or an aromatase inhibitor (16). Response was assessed from statistical analysis of the changes in tumour size. On completion of 12 weeks of endocrine therapy, there was significant regression of tumour size in 18 of the 43 patients. All 18 patients had tumours with ER concentrations of greater than or equal to 20 fmol mg-1 cytosol protein. Conversely all patients except one progressing on treatment had tumours with ER concentrations of less than 20 fmol mg-1 cytosol protein. This relationship applied for both premenopausal and post-menopausal patients. The overall response rate of patients with tumours of ER concentration greater than or equal to 20 fmol mg-1 cytosol protein was 60%.

‘MEDICAL OOPHORECTOMY’ With a long acting gonadotrophin releasing hormone

‘MEDICAL OOPHORECTOMY’ With a long acting gonadotrophin releasing hormone

"Medical oophorectomy" using a long-acting GNRH agonist--a possible new approach to the treatment of endometriosis.

Five women with endometriosis were given a daily dose of a potent long-acting GnRH agonist, D-Trp6-Pro9-Net-LHRH (GnRH-A) for 28 days in an attempt to suppress ovarian estrogen secretion. The mean level of estradiol (E2) during sampling over 24 hours decreased (P less than 0.01) from 62 +/- 11 to 10 +/- 1 pg/ml at the end of treatment. Mean concentrations of androstenedione, testosterone, estrone and E2 on day 28 of therapy were similar to those measured in oophorectomized women. The level of FSH was decreased (P less than 0.001) during GnRH-a, whereas that of LH was significantly (P less than 0.001) increased, suggesting differing intracellular control mechanisms for release of the two gonadotropins. Desensitization of the pituitary was demonstrated at the end of treatment by a complete lack of acute response of FSH or LH to the daily dose of GnRH-a. "Medical oophorectomy" provides a new approach to the treatment of endometriosis.