Induction Of Menopause Research Articles

5071 Impact of Estrogen Replacement Therapy on Bone Health in a Novel Non-human Primate Model of Postmenopausal Women Living with HIV

Abstract Disclosure: K. Sauter: None. D.L. Takahashi: None. G. Webb: None. H. Hofmeister: None. O. Varlamov: None. J. Sacha: None. P. Kievit: None. Current antiretroviral therapy (ART) regimens have rendered HIV a manageable chronic condition rather than a fatal disease, with people who initiate ART soon after infection achieving nearly normal life expectancy. As a consequence of increased survival, more women living with HIV (WLWH) will now undergo menopause and be subject to a disease burden that reflects age along with adverse skeletal consequences of postmenopausal estrogen deficiency. In addition to known bone loss and increased fracture risk in postmenopausal women, ART also causes decreased bone mineral density. Therefore ART-suppressed WLWH may have a compounded detrimental effect on bone due to long-term ART treatment combined with menopause that may be attenuated with estrogen replacement. Eleven rhesus macaques were infected intravenously with SIVmac239M and received ART two weeks post-infection (PI). All animals were ovariectomized (OVX) at 35 weeks PI and received estrogen implants (n=6) or cholesterol implants (n=5). Weekly blood samples were collected and animals were monitored longitudinally for body composition including bone mineral content (BMC) via dual x-ray absorptiometry (DEXA). Infection with SIV caused a significant decrease, -8.2%, in pelvis BMC after 14 days of peak viremia with SIV. These changes were not observed in the BMC of spine or extremities. BMC remained suppressed by ∼7% for an additional 25 weeks PI during ART treatment. Measurement of circulating bone turnover markers (BTMs), osteocalcin and C-terminal telopeptide of type 1 collagen (CTX), decreased post infection without significant improvement after ART suppression. Induction of menopause via OVX and loss of estrogen induced a drastic increase in BTMs with a much larger increase in CTX, indicating potential global bone loss due to OVX. Post-implant, the control animals’ pelvis BMC continued to decrease to -20.9% and pelvis BMD to -9.3% indicating that OVX further exacerbated the effect of SIV and ART. However, animals that received estrogen implants demonstrated marked improvement in both measures to greater than baseline. SIV and subsequent long-term ART negatively impact pelvic BMC and BMD and this effect is compounded by menopause in our model of post-menopausal WLWH. However, estrogen replacement post-menopause may attenuate these detrimental bone effects despite long-term ART treatment. Presentation: 6/1/2024

Lata Bisht, Minakshi Barmola, Mamta F Singh and Sonali Kulasari

ABSTRACT-Menopause is a natural process in women's reproductive life at the age of 40 to 50 years and leads to deficiency of estrogen causing various complications in women's health. Prunus amygdalusnuts are abundant source of various phytoestrogens and produces effect similar to that of estrogen and can be used in menopausal women in place of HRT. In the present study ovotoxicity and menopause wasinducedinfemaleratsby4-vinylcyclohexane diepoxide (165 mg/kg, i.p. five times a week for 15 days). After induction menopause the animals were treated with the paste of dried seeds of Prunus amygdalusat the doses of 100, 200 and 400 mg/kg, p.o. for 45 days. Blood estrogen level was checked before and after administration of VCD to confirm induction of menopause. After the treatment period of 45 days blood was collected from the animals, centrifuged and serum was separated and used for the estimation of estrogen, cholesterol,triglyceride,HDL,LDLandVLDL. Ovaries were isolated from the treated animals,keptinicecoldtrisbuffer,homogenized and centrifuged. The supernatant was used for the estimation of malondialdehyde (MDA) and antioxidant enzyme (superoxide dismutase and glutathione peroxidase). Results indicate that administration of seeds of Prunus amygdalus at different dose levels do not have anyeffectonserumestrogenlevelbutsignificantlyimprovedlipidprofileanddecreased atherogenic index in postmenopausal rats. Asignificant decrease in the MDAand increase in antioxidant enzymes level was observed in postmenopausal rats after treatment with paste of dried seeds of Prunus amygdalus. Results conclude that administration of seeds of Prunus amygdalus for a long period of time may improve the cardiovascular complications of women's health after menopause.

The Influence of Flaxseed on the body weight of Wistar Ovarioctomized Rats

Objectives : To evaluate the influence of flaxseed for a long period of time and its hormonal effects of weight loss in castrated rats. Methods : We used 21 Wistar rats that underwent bilateral oophorectomy for induction of menopause, randomly divided into three groups: control group (CG) (n = 7), which received a diet based on casein 10 percent; flaxseed group, that received a diet based on casein plus 25 percent of flaxseed (FG) (n = 7); and modified control group, that received a diet based on modified casein 10 percent and with addition of lipid and fibers (CGM) (n = 7). All diets were prepared according to the recommendations of the AIN 93, the animals were kept under controlled temperature (22oC ±2oC) and adequate lighting (light/dark cycle of 12 to 12 hours). The animals received food and water (adlibitum). The rats were anesthetized with Thiopentax® for blood collection by cardiac puncture for the determination of 17b-estradiol and collection of tissues (liver, bladder and uterus).

Blueberries improve glucose tolerance without altering body composition in obese postmenopausal mice.

ObjectiveMetabolic syndrome (MetS) risk increases significantly during menopause and remains elevated post-menopause. Several botanicals, including blueberries (BB), have been shown to delay MetS progression, but few studies have been conducted in postmenopausal animal models. Here, we examined the effects of BB supplementation on obese postmenopausal mice using a chemically-induced menopause model.Design and MethodsAfter induction of menopause, mice were fed a high-fat diet or the same diet supplemented with 4% BB powder for 12 weeks. Body weight and body composition were measured, and mice were subjected to glucose and insulin tolerance tests. Serum triglycerides and adiponectin were measured, and liver histology and hepatic gene expression were assessed. Results: Menopausal and BB-supplemented mice had significantly higher body weights and fat mass than control mice, while menopausal mice had impaired glucose tolerance and higher serum triglycerides when compared with control and BB-supplemented mice. Menopausal mice also had hepatic steatosis that was prevented by BB supplementation and correlated with expression of genes involved in hepatic fatty acid oxidation.ConclusionsWe conclude that BB supplementation prevents the glucose intolerance and hepatic steatosis that occur in obese postmenopausal mice, and that these effects are independent of body weight.

Computable Linearizations of Well-partial-orderings

Lymphangioleiomyomatosis (LAM) is a rare disease of unknown aetiology which mainly affects women of reproductive age. A growing body of evidence suggests a relation between the disease and estrogenic hormones. In particular, pregnancy and use of estrogens favour the progression of the disease, which is in turn slowed down by menopause. These observations suggested already in the past a treatment strategy based on hormonal manipulation: discontinuation of estrogens containing medications, avoiding pregnancy, inhibition of estrogens activity and induction of menopause. In the present study, conducted on a relatively large population for a rare disease, we sought to show the hormonal manipulation's positive effects for the survival rate. 36 women suffering from LAM were evaluated between January 1985 and March 2005. All our patients were treated with hormonal therapy, following different schemes. The response to the treatment was evaluated in all patients with arterial blood sampling, lung function tests (total body plethysmography, DLCO), measurement of the hormones in the blood, chest and abdomen CT scan. The survival rate since the clinical onset was 97% at the 5 year timepoint, 90% at 10 years, and 71% at 25 years. Previous studies, conducted before the introduction of the hormonal treatment showed a survival rate of 20% at 10 years. Our results highlight the role of the hormonal manipulation as a mainstay in the treatment of LAM, with the capability of reducing mortality and improving the quality of life as well.

Risk of chemotherapy induced menopause: More detailed data will lead to improved quality of life

Women now live longer than ever following a diagnosis of breast cancer. Thus, survivorship issues and quality of life following primary treatment of breast cancer are assuming increasing importance. In younger women, the induction of menopause either deliberately or as a side-effect of chemotherapy forms an important piece of the survivorship issue. Paradoxically, induction of menopause following adjuvant chemotherapy while positive in terms of anti-cancer efficacy in some patients is nonetheless one of the big negatives in terms of quality of life, especially for the youngest women. Menopausal symptoms such as hot flashes, vaginal dryness and ‘aches and pains’ are clearly relevant but fertility impairment is also important, particularly in the very young women of less than 35 years of age. Unfortunately, most studies of adjuvant chemotherapy in premenopausal women with breast cancer have either not recorded menstrual status following therapy or have recorded it in an incomplete fashion. Thus, although some papers have reported the incidence of amenorrhoea following chemotherapy, they have not collected sufficient data to report whether amenorrhoea becomes permanent or is only temporary, and if so, for what time periods. Furthermore, there has been little reporting of the subsequent menstrual history of women who become temporarily amenorrhoeic following chemotherapy but resume menses, or of those whose menstrual cycles are

Impact on quality of life of adjuvant therapy for breast cancer

Late toxicities of adjuvant chemotherapy and side effects of endocrine therapy may cause long-term quality-of-life impairments for some individuals who have been treated for breast cancer. Chemotherapy has been associated with durable effects on cognitive function and fatigue and with the induction of menopause. Endocrine therapies can increase menopausal and sexual symptoms and can contribute to weight gain. Overall, however, quality of life is good for the majority of breast cancer survivors who have received adjuvant systemic therapy. Behavioral interventions that target fatigue and sleep disturbance may further enhance quality of life.

Estrogen and estrogen plus progestin act directly on the mammary gland to increase proliferation in a postmenopausal mouse model.

Hormone replacement therapy (HRT) with ovarian hormones is an important therapeutic modality for postmenopausal women. However, a negative side effect of HRT is an increased risk of breast cancer. Surgical induction of menopause by ovariectomy (OVX) in mice is an experimental model that may provide insights into the effects of hormone replacement therapy on the human breast. We have developed a mouse model of early and late postmenopausal states to investigate the effects of HRT on the normal mammary gland. The purpose of this study was to determine if HRT-induced proliferation was due to the direct action of the hormones on the mammary gland, or mediated systemically by hormones or growth factors produced elsewhere in the body. Estrogen (E) or E plus the synthetic progestin, R5020, were implanted directly into the mammary glands of early (1 week post OVX) and late (5 week post OVX) postmenopausal mice instead of administration by injection. We report that responses of early and late postmenopausal mice to implanted hormones were the same as those observed previously with systemically administered hormones. Implanted E conferred an enhanced proliferative response in the late postmenopausal gland characterized morphologically by enlarged duct ends. E+R5020 implants induced similar degrees of cell proliferation in both postmenopausal states but the morphological responses differed. Ductal sidebranching was observed in early postmenopausal mice, whereas duct end enlargement was observed in late postmenopausal mice. The differences in morphological response to E+R5020 in 5 week post OVX were associated with an inability of E to induce progesterone receptors (PR) in the late postmenopausal gland. The responses of the late postmenopausal glands to E and E+P were very similar to that observed previously in immature pubertal glands in ovary-intact mice. In pubertal mice, PR cannot be induced by E unless the mammary gland is pre-treated with EGF-containing implants. Similarly, herein pre-treatment of the late postmenopausal mammary gland with EGF-containing implants restored PR induction by E. Thus, EGF may determine the sensitivity of the mammary gland to E and E+P in late postmenopause and at puberty.

Nursing Care of a Patient after Breast Surgery

The most widely used palliative measure for inoperable cancer of the breast is irradiation. Small doses of x-ray applied to localized areas of metastasis, especially those involving bony structures can shrink the metastatic growth and reduce pain. In recent years, hormones have also been used as palliative agents. Estrogens and androgens, however, are generally administered only after irradiation therapy has proved to be inadequate. The therapeutic value of an artifically induced menopause in the palliative treatment of breast cancer is, at present, still a debatable one. Some surgeohs believe that all patients with carcinoma of the breast should undergo surgical removal or irradiation treatment of the ovaries to produce an artificial menopause, but others feel that the induction of menopause does not affect the disease. All agree, however, that in cases where all other available therapies have failed to control metastases, the production of an artificial menopause should be considered.

ATYPICAL ENDOMETRIAL HYPERPLASIA SIMULATING ADENOCARCINOMA

Benign hyperplastic lesions of the endometrium have often been mistaken for adenocarcinoma. Areas of Swiss-cheese endometrium of considerable size may be found in normally functioning organs. The reaction of the endometrium to ovarian hormones is not always the same in all its parts. Young immature endometrium are highly responsive to the growth effect of estrogen and refractory to the differentiating hormone progesterone. The reverse is true in more mature endometrial elements. When squamous areas occur in a benign hyperplastic endometrium they are not necessarily evidence of malignancy. The gland characteristics should be used for diagnosis. Curettage or curettage plus radiologic induction of menopause was used in 18 described cases of uterine bleeding. All showed histologic changes which might have been mistaken for adenocarcinoma. 26 cases of atypical hyperplasia with subsequent hysterectomy without preliminary radiation are more extreme than the curettage cases therefore the simulation of cancer is more perfect. The absence of any gross lesion was incompatible with the malignancy diagnosis. There was no evidence of penetration of the basement membrane or of myometrial involvement. Cell characteristics are useful in some cases but not in others. It is impossible to decide whether or not a lesion is a cancer based on microscopic examination.