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PubMed2001

The effect of ovariectomy and ovarian steroid treatment on growth hormone and insulin-like growth factor-I levels in the rat femur.

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are known to play an important role in bone metabolism. The regulation of plasma levels of GH and IGF-I by ovarian steroids is well known, however, their effect on local GH and IGF-I is still unclear. In this study, we investigated the effect of ovariectomy and ovarian steroid treatment on the femur GH and IGF-I levels as well as on bone density in the rat. Nine month-old rats were ovariectomized (OVX) or sham-operated (SHAM) and 9 weeks after the surgery they were treated with daily s.c. injections of either 17beta-estradiol (OVX + E), progesterone (OVX + P), or vehicle (OVX + V) for another 10 weeks. GH and IGF-I levels in the femur extracts were measured by specific radioimmunoassay (RIA). Ovariectomy decreased GH and had no effect on IGF-I levels. Estradiol treatment increased femur GH and IGF-I levels compared to SHAM rats. Progesterone restored GH and increased IGF-I levels. Ovariectomy decreased, estrogen restored and progesterone partially restored femur bone density. Our results demonstrate that ovariectomy and ovarian steroids modulate the levels of GH and IGF-I in the bone of aged OVX rats. However, these effects appear to be limited to supraphysiological concentrations of estradiol and progesterone.

Animals↗
PubMed2003

Increased bone remodeling due to ovariectomy dramatically increases tumoral growth in the 5T2 multiple myeloma mouse model.

Bone destruction is the main clinical consequence of multiple myeloma (MM). It is known that a "vicious circle" exists between bone and myeloma cells with plasma cells stimulating bone cells, which in return stimulate the neoplastic growth. We hypothesized that an accelerated bone remodeling induced by ovariectomy (OVX) could provide a more fertile environment for the myeloma cell growth. Ovariectomy performed on C57BL/KaLwRij mice resulted in reduced trabecular bone volume and increased osteoclast number. To test our hypothesis, we ovariectomized C57BL/KaLwRij mice one week before injection of 5T2MM myeloma cells. A non-OVX 5T2MM group was used as control. Ovariectomy increased the tumor growth and induced an earlier development of osteolytic lesions. OVX 5T2MM mice were euthanized at 10 weeks, instead of 16 weeks, for the non-OVX 5T2MM, mice because of the accelerated development of disease in OVX animals. Treatment of OVX 5T2MM mice with pamidronate reduced osteolysis but had little effect on the time development of the tumor. This combined model (ovariectomy + 5T2MM) confirmed the interdependence of bone and myeloma cells and could explain the some sudden burden of indolent MM into aggressive MM in humans.

Animals↗
PubMed1999

Long-term deprivation of oestrogens by ovariectomy potentiates beta-amyloid-induced working memory deficits in rats.

1 In the present study, we examined whether deprivation of oestrogens by ovariectomy could modify learning and memory deficits caused by a continuous intracerebroventricular (i.c.v.) infusion of amyloid beta-peptide (Abeta), the major constituent of senile plaques in AD. 2 Neither long-term (3 months) nor short-term (1 month), deprivation of oestrogens by ovariectomy caused a significant impairment in spatial learning and memory in a water maze and spontaneous alternation behaviour in a Y-maze. 3 A continuous i.c.v. infusion of Abeta-(1-42) caused spatial learning and memory deficits in both ovariectomized and sham-operated rats. 4 The Abeta-induced working memory deficits were significantly potentiated in ovariectomized rats compared with sham-operated rats when mnemonic ability was examined 3 months after ovariectomy. 5 These results suggest that long-term deprivation of oestrogens induced by ovariectomy increases susceptibility to memory deficits produced by Abeta-(1-42) in rats.

Amyloid beta-Peptides↗
PubMed2005

Vascular effects of ovariectomy and chronic oestrogen treatment in rats: controversy or experimental protocol diversity?

Several clinical studies have indicated that oestrogens have protective properties on the cardiovascular system. Although the beneficial effect has been attributable, at least in part, to their ability to stimulate the endothelial formation of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF), the underlying mechanism still remains unclear. In a study from this issue of British Journal of Pharmacology, Nawate et al. have examined the effects of rat ovariectomy and chronic treatment with 17beta-oestradiol on the endothelial function as assessed ex vivo. The data indicate that acetylcholine-induced endothelium-dependent relaxations of the isolated mesenteric artery are affected by neither ovariectomy nor chronic hormonal treatment. Despite the maintained endothelium-dependent relaxation, the contribution of the two major endothelial factors NO and EDHF was changed. Indeed, ovariectomy increased the NO-mediated component of the relaxation, most likely as a consequence of the downregulation of the physiological allosteric inhibitor of endothelial NO synthase, caveolin-1. In addition, ovariectomy decreased the EDHF-mediated component of the relaxation and membrane hyperpolarization of the smooth muscle cells, an effect which might be explained by a concomitant decrease of the expression of the gap junction connexin-40 and connexin-43. Furthermore, chronic administration of 17beta-estradiol to ovariectomized rats normalized all these effects. This study provides further experimental evidence indicating that the hormonal status plays a determinant role in the control of the endothelial formation of both NO and EDHF.

Animals↗
PubMed2000

Effect of ovariectomy on bone remodeling adjacent to hydroxyapatite-coated implants in the tibia of mature rats.

PURPOSE: The purpose of this study was to examine the effects of estrogen deficiency on bone remodeling adjacent to implants in the tibia of mature rats. MATERIALS AND METHODS: Hydroxyapatite-coated implants were placed bilaterally in the proximal metaphysis of the tibia of 18 female Wistar rats (48 weeks old), and ovariectomy was performed 168 days later. As a control, sham ovariectomy was performed in a similar group of 18 rats. Six animals from each group were killed at 28, 84, and 168 days after ovariectomy. Undecalcified sections were prepared, and changes in the bone tissue around the implants were evaluated histologically. Histomorphometric measurements were made with a computer-based image analyzer to quantify the unit bone mass around each implant and the amount of implant-bone contact. RESULTS: In the cortical bone area, ovariectomy induced only a slight decrease in bone contact with the implant, compared with that in the sham-operated rats. However, both the bone volume around the implant and implant-bone contact were significantly decreased in the cancellous bone area in ovariectomized rats compared with the sham-operated rats. CONCLUSION: Thinning of the bone trabeculae holding dental implants may occur with estrogen deficiency.

Animals↗
PubMedDate not supplied

Evaluation of the harmonic scalpel for laparoscopic bilateral ovariectomy in standing horses.

OBJECTIVE: To evaluate use of the Harmonic Scalpel (Ethicon Endo-Surgery Inc., Cincinnati, OH) for performing laparoscopic bilateral ovariectomy in standing horses. STUDY DESIGN: Experimental study. ANIMALS: Eight mares aged 2-20 years and weighing 410-540 kg. METHODS: Standing laparoscopic bilateral ovariectomy was performed in 8 mares with normal reproductive tract anatomy. The Harmonic Scalpel (an ultrasonically activated instrument) was used to simultaneously transect and obtain hemostasis of the ovarian pedicle. Necropsy was performed on 4 mares 3 days after surgery and 4 mares 30 days after surgery. Gross and histopathologic evaluation of the ovarian pedicles was performed to characterize tissue reaction. RESULTS: Complete hemostasis of the ovarian pedicles was obtained in all mares. Median transection time for the ovarian pedicle was 28 minutes. Postoperative complications included transient fever, moderate subcutaneous emphysema, and incisional seroma formation. On necropsy examination, there were no signs of generalized peritonitis, postoperative hemorrhage, or adhesion formation. Mild to moderate acute inflammation and scar formation with moderate chronic inflammation at the ovarian pedicle was found at 3 and 30 days. Median depth of coagulation necrosis at 3 days was 2.87 mm. CONCLUSIONS: The Harmonic Scalpel appears to provide reliable hemostasis of the ovarian pedicle during elective laparoscopic ovariectomy in horses. Clinical Relevance-The Harmonic Scalpel represents a safe alternative to other methods of hemostasis during elective laparoscopic ovariectomy in horses.

Animals↗
PubMedDate not supplied

Monopolar versus bipolar electrocoagulation in canine laparoscopic ovariectomy: a nonrandomized, prospective, clinical trial.

OBJECTIVE: To compare the effect of using monopolar (MEC) or bipolar electrocoagulation (BEC) on surgical time for laparoscopic ovariectomy in dogs and to evaluate the influence of age, weight and obesity, and estrus or pseudopregnancy on surgical time. STUDY DESIGN: Prospective, nonrandomized, clinical trial. ANIMALS: One hundred three female dogs. METHODS: Laparoscopic ovariectomy was performed with MEC or BEC by 1 surgeon using a standard protocol. Surgical time was recorded for the different procedural stages and was statistically evaluated for differences between MEC and BEC (chi(2), Student t test, and ANOVA). The influence of significant variables was analyzed using multiple linear regression analysis. RESULTS: Mean surgical time was 47 minutes (range, 27 to 110 minutes). With BEC, surgical time was significantly shorter (41 minutes; P <.001) than with MEC (53 minutes). Obesity (56 vs. 42 minutes; P <.001) and intraoperative mesovarial bleeding (56 vs. 46 minutes; P =.03) increased surgical time. Dog age, estrus, and pseudopregnancy did not significantly influence surgical time. CONCLUSIONS: BEC decreased laparoscopic ovariectomy time, decreased intraoperative hemorrhage, and, with the technique used, facilitated exteriorization of the ovaries. CLINICAL RELEVANCE: Laparoscopic ovariectomy can be performed more rapidly when using BEC instead of MEC and with less risk of mesovarial hemorrhage.

Animals↗
PubMed1986

The effect of ovariectomy on lipoprotein metabolism during a period of one year.

In a follow-up study over one year the influence of sex hormones on lipoprotein metabolism in women after ovariectomy was investigated. During this relatively long period we could observe several changes of lipid and apolipoprotein levels in serum which may be caused by adaptive processes after withdrawal of sex hormones. The first phase of variation of lipids and apolipoproteins (2 weeks after ovariectomy) is strongly influenced by the operation trauma and characterized by a decrease of apo A-I, apo A-II, TC levels and an increase of the triglyceride level. The second phase (6-18 weeks after operation) shows an increase of the levels of apolipoprotein of HDL (apo A-I and apo A-II) and also apo C-II and apo C-III. The pattern in the third phase (one year after operation) differs from that of the two earlier phases and is similar to that in the natural postmenopausal state (elevation of apo B, TC, nonsignificant elevation of apo A-I and significant elevation of apo A-II). It seems that ovariectomy causes permanent changes of the LDL-level whereas the fluctuation of HDL is temporary. The late changes in the lipoprotein spectrum following ovariectomy in the reported direction may be important for the increase of ischemic heart disease observed by many investigators.

Adult↗
PubMed2002

Effects of ovariectomy and estrogen and androgen treatment on sildenafil-mediated changes in female genital blood flow and vaginal lubrication in the animal model.

OBJECTIVE: Our purpose was to investigate the effects of ovariectomy and estradiol and testosterone treatment on sildenafil- induced changes in genital hemodynamics and vaginal lubrication. STUDY DESIGN: Female New Zealand White rabbits were either kept intact or underwent ovariectomy. Two weeks after ovariectomy, animals were treated with vehicle, testosterone, or a combination of estradiol and testosterone for 14 days. Genital hemodynamics and vaginal lubrication were recorded at the end of the treatment period. RESULTS: Ovariectomy caused a marked decrease in vaginal lubrication but did not significantly alter genital hemodynamics. In contrast to testosterone treatment of ovariectomized animals, estradiol treatment significantly increased genital blood flow and vaginal lubrication above that observed in control animals. Sildenafil administration caused a significant increase in genital hemodynamics irrespective of the hormonal status. CONCLUSION: This study suggests that estradiol but not testosterone modulates genital hemodynamics and that sildenafil enhances genital blood flow irrespective of hormonal status.

Animals↗
PubMed1992

Ovariectomy selectively reduces the concentration of transforming growth factor beta in rat bone: implications for estrogen deficiency-associated bone loss.

Previous work showed that production of transforming growth factor beta (TGF-beta) by osteoblast-like rat UMR 106 cells was increased by 17 beta-estradiol at physiological concentrations. To determine whether ovariectomy alters the concentration of TGF-beta in rat long bones, female Sprague-Dawley rats were either sham-operated (n = 19) or ovariectomized (n = 19), pair-fed a semisynthetic diet for 6 weeks, and sacrificed. Tibial and femoral diaphyses were removed and extracted by demineralization. Ovariectomy lowered serum estrogen; did not alter body weight, serum magnesium, or serum 1,25-dihydroxyvitamin D; and produced only modest differences in serum calcium and phosphate concentrations. Hydroxyproline was higher and extractable protein was lower in bones from ovariectomized rats than in bones from sham-operated rats; calcium content did not differ between the two groups of animals. Ovariectomy lowered the concentration of TGF-beta in bone but did not change the concentration of insulin-like growth factors I or II compared with values in bone from control animals. The reduction of bone TGF-beta was evident 6 weeks after surgery but not at 3 weeks. Treatment of ovariectomized rats with estrogen eliminated the TGF-beta deficit. To determine whether 17 beta-estradiol increased TGF-beta production by normal bone cells, mouse osteoblasts were treated for 2 days with 17 beta-estradiol. The production of TGF-beta was increased almost 2-fold by 1 nM 17 beta-estradiol, and short-term treatment stimulated the intracellular accumulation of TGF-beta 1 mRNA. We conclude that ovariectomy reduces deposition of TGF-beta in rat bone and that diminished skeletal TGF-beta could play a role in the pathogenesis of bone loss, fractures, and microfractures that occur in estrogen-deficient states. Our results support the possibility that estrogen and bone TGF-beta may be necessary for normal maintenance of the skeleton in female rats.

Animals↗
PubMed2003

Effects of ovariectomy and estrogen replacement on basal and pelvic nerve stimulated vaginal lubrication in an animal model.

The goal of this study was to investigate the effects of ovariectomy and estrogen replacement on vaginal tissue integrity and vaginal lubrication in basal conditions and in response to pelvic nerve stimulation (PNS). Two weeks after ovariectomy, female New Zealand White rabbits were administered vehicle or estradiol (200 micrograms/day) for an additional 2 weeks. Ovariectomy caused significant vaginal atrophy and diminished vaginal lubrication in the basal state and after PNS, compared to intact controls. Estrogen replacement normalized lubrication values and tissue wet weight to control levels. In conclusion, vaginal tissue integrity and lubrication are diminished by ovariectomy and are normalized by estrogen replacement.

Animals↗
PubMed2003

The effect of ovariectomy and estradiol on rabbit bladder smooth muscle contraction and morphology.

PURPOSE: The bladder can be considered a target organ for the actions of estrogen. Decreases in circulating estrogen after menopause have been associated with bladder dysfunctions, including incontinence and detrusor instability. We determined the effects of estrogen on rabbit bladder contractile function and morphology. MATERIALS AND METHODS: Female New Zealand White rabbits were ovariectomized or sham operated and treated with vehicle or estradiol (1 mg/kg weekly) for 5 weeks. Serum estradiol concentration was monitored every 2 weeks. After treatment each rabbit was anesthetized, the bladder was catheterized, cystometry was performed, and the bladder was removed for contractile and morphological studies. Apoptosis in paraffin embedded rabbit bladder tissue was detected using in situ end-labeling, specifically terminal deoxynucleotidyl-transferase nick end labeling or the TUNEL assay. RESULTS: Ovariectomy resulted in a 50% decrease in circulating estrogen and estradiol treatment resulted in a 5-fold increase. Ovariectomy had no significant effects on bladder capacity, micturition pressure or bladder weight; whereas estradiol treatment resulted in significant increases in bladder capacity and bladder weight. Ovariectomy resulted in a decreased rate of tension generation in response to field stimulation, carbachol and KCl. Estradiol resulted in increased contractile responses to FS and carbachol, and an increased rate of tension generation for carbachol and KCl. Histologically ovariectomy resulted in significant urothelial apoptosis, which was not present in the sham operated or estradiol treated groups. Estradiol treatment resulted in the appearance of large cytoplasmic vacuoles in the urothelium and significant smooth muscle hypertrophy. CONCLUSIONS: These findings demonstrate that bladder function and structure can be significantly affected by modulating the circulating estrogen level. In addition, estrogen given in pharmacological doses can have a significant hypertrophic effect on bladder smooth muscle, resulting in increased contractile function.

Animals↗
PubMedDate not supplied

Paralumbar fossa laparoscopic ovariectomy in horses with use of Endoloop ligatures.

OBJECTIVE: The purposes of this study were to develop a technique of paralumbar fossa laparoscopic ovariectomy using Endoloop ligatures and to avoid a laparotomy incision for ovary removal by using a 33-mm diameter muscle spreader trocar-cannula unit. ANIMALS OR SAMPLE POPULATION: Seven mares. METHODS: Bilateral laparoscopic ovariectomy was performed under general anesthesia in two horses and under neuroleptanalgesia and local anesthesia in five standing mares. Ovaries were approached from the ipsilateral paralumbar fossa through two portal sites located in the paralumbar fossa and a third between the 17th and 18th ribs. Insufflation of the abdominal cavity was achieved using an automatic carbon dioxide insufflator. Two Endoloop ligatures were placed on the mesovarium. The cannula, located in the center of the paralumbar fossa, was removed, and a 33-mm diameter trocar-cannula unit, with a cone-shaped muscle spreader extremity, was inserted through the same portal. The mesovarium was transected between the ovary and the ligatures. The ovaries were removed from the abdomen through the 33-mm diameter cannula. The abdominal wall was closed in a routine manner. RESULTS: No major complications occurred during or after surgery. CONCLUSION: Paralumbar fossa laparoscopic ovariectomy in mares using Endoloop ligatures and the 33-mm diameter trocar-cannula unit was an effective technique for ovariectomy of normal ovaries in this study. CLINICAL RELEVANCE: Endoloop ligatures provide a viable alternative for laparoscopic ligation of ovarian pedicles in mares.

Animals↗
PubMedDate not supplied

Ventral abdominal approach for laparoscopic ovariectomy in llamas.

OBJECTIVE: To evaluate a technique for laparoscopic ovariectomy by a ventral abdominal approach in the llama. STUDY DESIGN: Prospective evaluation. ANIMAL POPULATION: Six healthy adult female llamas, aged 2 to 6 years. METHODS: Laparoscopic ovariectomy was performed with the llamas in a 30-degree Trendelenburg position. The mesovarium and proper ligament of the ovary were isolated, and two Hulka clips were placed in opposite directions across each mesovarium and proper ligament of the ovary. Ovaries were removed through either the instrument cannula or instrument portal. RESULTS: The ovaries, mesovarium, and proper ligaments of the ovaries were easily identified using laparoscopy by a ventral abdominal approach. The Hulka Clip Applicator was easy to use, and the Hulka Clips provided secure hemostasis of the vessels within the mesovarium. Mean duration of surgery was 35 minutes (range, 17 to 85 minutes). Two llamas were depressed after surgery but improved within 24 hours. No other complications occurred during an 18-month follow-up period. CONCLUSIONS: Laparoscopic ovariectomy in the llama was facilitated by the use of Hulka Clips placed across the mesovarium and proper ligament of the ovary. CLINICAL RELEVANCE: Laparoscopic ovariectomy in the llama can be accomplished easily with few complications.

Animals↗
PubMedDate not supplied

Ovariectomy ameliorates dextromethorphan--induced memory impairment in young female rats.

We have previously found that dextromethorphan (DM), over-the-counter cough suppressant, impairs memory retention in water maze task, when it is repeatedly administrated to adolescent female rats at high doses. In this study we examined first if ovariectomy ameliorates the DM-induced memory impairment in female rats, and then whether or not the DM effect is revived by estrogen replacement in ovariectomized female rats. Female rat pups received bilateral ovariectomy or sham operation on postnatal day (PND) 21, and then intraperitoneal DM (40 mg/kg) daily during PND 28-37. Rats were subjected to the Morris water maze task from PND 38, approximately 24 h after the last DM injection. In probe trial, goal quadrant dwell time was significantly reduced by DM in the sham operated group, however, the reduction by DM did not occur in the ovariectomy group. When 17beta-estradiol was supplied to ovariectomized females during DM treatment, the goal quadrant dwell time was significantly decreased, compared to the vehicle control group. Furthermore, a major effect of estrogen replacement was found in the escape latency during the last 3 days of initial learning trials. These results suggest that ovariectomy may ameliorate the adverse effect of DM treatment on memory retention in young female rats, and that estrogen replacement may revive it, i.e. estrogen may take a major role in DM-induced memory impairment in female rats.

Animals↗
PubMed2006

Radiographic assessment of bone density around integrated titanium implants after ovariectomy in rats.

OBJECTIVES: This study evaluated the influence of ovariectomy 8 weeks after implant placement on bone integrated to titanium implants. MATERIAL AND METHODS: Thirty-eight female rats were submitted to a titanium implant at the tibiae proximal methaphysis. After a healing period of 8 weeks the animals were randomly divided into three groups: control (CTL-10 animals), sham-operated (SHAM-14 animals) and ovariectomy (OVX-14 animals). The CTL group was then sacrificed in order to confirm integration of the implant. The SHAM group was submitted to fictitious surgery and the OVX group was submitted to bilateral ovariectomy. After 12 weeks post-implant placement, the SHAM and OVX groups were sacrificed. In order to confirm the systemic osteopenia in rats, a dual-energy X-ray absorptiometry (DXA) was performed. For the evaluation of bone density, digital radiographs were taken. The grey level of the bone adjacent to implant was measured using image software and the bone density was calculated at six points on both sides of the implant. RESULTS: Densitometry measurements of the femur confirmed systemic bone mass loss in the OVX group. Individualized bone analyses of different regions surrounding the implant showed a significantly lower radiographic bone density (P < 0.05) in the cancellous region of the OVX group (77.48 +/- 23.39 grey levels) when compared with the CTL and SHAM groups (91.61 +/- 32.10 and 102.57 +/- 32.50 grey levels, respectively). CONCLUSIONS: The present study showed a decrease of the radiographic bone density in the cancellous region of bone around titanium implants placed 8 weeks before ovariectomy in rats.

Absorptiometry, Photon↗
PubMed2002

Ovariectomy increases mitogens and platelet-induced proliferation of arterial smooth muscle.

Experiments were designed to determine how ovariectomy modulates mitogenic factors in platelets and how these factors affect proliferation of coronary arterial smooth muscle. Platelet-derived growth factors (PDGF(AB) and PDGF(BB)), transforming growth factors (TGF-beta(1) and TGF-beta(2)), and vascular endothelial growth factor (VEGF(165)) were quantified in platelet lysates and platelet-poor plasma from adult gonadally intact and ovariectomized female pigs by ELISA. Proliferation of cultured coronary arterial smooth muscle cells (SMCs) from both groups of pigs was determined in response to autologous or heterologous platelet lysates. Platelet concentrations of PDGF(BB), but not PDGF(AB), TGF-beta(1), and TGF-beta(2), increased with ovariectomy. VEGF(165) was not detected in platelets from either group. Proliferation of SMCs from ovariectomized females was significantly greater on exposure to autologous or heterologous platelet lysates than proliferation of SMCs from intact females. These results indicate that ovariectomy increases concentrations of PDGF(BB) in platelets. Higher levels of PDGF(BB) in platelets in synergy with other platelet-derived products could contribute to increased proliferative arterial response to injury after ovariectomy.

Animals↗
PubMed2003

Effects of ovariectomy on aggregation, secretion, and metalloproteinases in porcine platelets.

Differences in the aggregation and release of growth factors including matrix metalloproteinases (MMPs) after loss of ovarian hormones could contribute to an exaggerated response to injury in arteries of ovariectomized animals. Therefore, experiments were designed to compare aggregation, dense granular ATP release, expression of MMPs (MMP-2, MMP-9, and MMP-14) and tissue inhibitors of metalloproteinase (TIMP-1 and TIMP-2) in circulating platelets from sexually mature (7 mo old) gonadally intact and ovariectomized (4 wk) female pigs. Numbers of circulating platelets did not change after ovariectomy, but the percentage of reticulated platelets increased significantly. Platelet aggregation and dense granular ATP secretion also increased significantly with ovariectomy. In platelet lysates, active MMP-2 increased, whereas MMP-14 significantly decreased, after ovariectomy; the expression of TIMP-1, TIMP-2, and P-selectin did not change. These results suggest that platelet turnover, aggregation, and ATP secretion increase with ovariectomy. Also, ovarian hormones selectively regulate the expression and activity of MMPs in porcine platelets. Increased platelet aggregation and activity of MMP-2 would alter platelet-platelet and platelet-vessel wall interactions, contributing to an exaggerated response to injury with loss of ovarian hormones.

Adenosine Triphosphate↗