Raymond Galea | University of Malta (original) (raw)
Papers by Raymond Galea
Journal of Diabetes and its Complications, 2016
Background: Studies of the effect of type 2 diabetes (T2D) on bone mineral density (BMD have prod... more Background: Studies of the effect of type 2 diabetes (T2D) on bone mineral density (BMD have produced conflicting results, possibly due to failure to adjust for potential confounding factors. Nonetheless, T2D has consistently been associated with increased fracture risk, suggesting that other factors might play a role. Objective: This study assesses the relationship between T2D and BMD at the femoral neck and spine in diabetic and non-diabetic subjects, after adjusting for multiple covariates which may affect BMD. Intervertebral disc height was also investigated in view of its possible relation to fracture risk. Methods: A cross-sectional study of 100 patients with T2DM of at least 5 years duration and 86 non-diabetic subjects was carried out. Results: There were no significant differences in T scores in either the spine or femoral neck after adjustment for potential confounding variables between T2D subjects and controls. Diabetic patients had a statistically lower intervertebral disc height between the 2nd and 3rd lumbar vertebrae (D3) after adjustment for potential confounders (p = 0.004). Urinary albumin:creatinine ratio, total cholesterol, LDL-cholesterol and cigarette smoking were independently associated with lower height of D3 in diabetic subjects. Conclusions: There is no significant independent association between T2D and BMD. However we found a novel association of significantly lower disc height in patients with T2D. This may contribute to the increased vertebral fracture risk in subjects with T2D. Further studies are needed to investigate the relationship of disc height, T2D and fracture risk.
International Journal of Environmental Research and Public Health, 2022
The characterization of human microbiota and the impact of its modifications on the health of ind... more The characterization of human microbiota and the impact of its modifications on the health of individuals represent a current topic of great interest for the world scientific community. Scientific evidence is emerging regarding the role that microbiota has in the onset of important chronic illnesses. Since individuals spend most of their life at work, occupational exposures may have an impact on the organism’s microbiota. The purpose of this review is to explore the influence that different occupational exposures have on human microbiota in order to set a new basis for workers’ health protection and disease prevention. The literature search was performed in PubMed, Cochrane, and Scopus. A total of 5818 references emerged from the online search, and 31 articles were included in the systematic review (26 original articles and 5 reviews). Exposure to biological agents (in particular direct contact with animals) was the most occupational risk factor studied, and it was found involved in...
Backgound: Padina pavonica appears to improve the bone mineral density at the lumbar spine and at... more Backgound: Padina pavonica appears to improve the bone mineral density at the lumbar spine and at the hip in post-menopausal women (1). The aims of this project are to compare it to other treatments available on the market, for the treatment of post-menopausal osteoporosis and to shed more light on the mechanism of action of Padina pavonica. Aims and Objectives: The aim of this research-based experiment is to compare the ability of osteoblasts treated with the extract of Padina pavonica (EPP) to differentiate and fix calcium, with osteoblasts treated with raloxifene and oestradiol. Raloxifene, a selective oestrogen receptor modulator (SERM) and oestradiol in the form of hormone replacement therapy (HRT) are drugs normally used in the management of post-menopausal osteoporosis. A secondary aim is to determine whether the extract exerts its action by modulating the oestrogen receptor. This would imply that the extract of Padina pavonica has a SERM-like activity and is thus potentially...
Sustainability, 2021
The psychology of sustainability and sustainable development emphasizes the value to ensure healt... more The psychology of sustainability and sustainable development emphasizes the value to ensure health and well-being in different environments, including workplaces. Chronic exposure to noise can cause several extraordinary effects and involve all the systems of the human organism. In addition to cardiovascular, gastrointestinal, and immune effects, the data in the literature show alterations in behavioral disturbances, memory capacity, and cognitive performance. Through this systematic review, the authors try to find out the main neurobehavioral alterations in the case of occupational exposure to noise. The literature review included articles published in the major databases (PubMed, Cochrane Library, Scopus, Embase), using a combination of some relevant keywords. This online search yielded 4434 references; after selection, the authors analyzed 41 articles (4 narrative reviews and 37 original articles). From this analysis, it appears that the main symptoms are related to psychological...
International Journal of Environmental Research and Public Health, 2020
Allergic disorders in the agriculture sector are very common among farm workers, causing many inj... more Allergic disorders in the agriculture sector are very common among farm workers, causing many injuries and occupational diseases every year. Agricultural employees are exposed to multiple conditions and various allergenic substances, which could be related to onset of anaphylactic reactions. This systematic review highlights the main clinical manifestation, the allergens that are mostly involved and the main activities that are usually involved. This research includes articles published on the major databases (PubMed, Cochrane Library, Scopus), using a combination of keywords. The online search yielded 489 references; after selection, by the authors, 36 articles (nine reviews and 27 original articles) were analyzed. From this analysis, the main clinical problems that were diagnosed in this category were respiratory (ranging from rhinitis to asthma) and dermatological (eczema, dermatitis, hives) in nature, with a wide symptomatology (from a simple local reaction to anaphylaxis). The ...
International Journal of Environmental Research and Public Health, 2020
Chronic exposure to urban noise is harmful for auditory perception, cardiovascular, gastrointesti... more Chronic exposure to urban noise is harmful for auditory perception, cardiovascular, gastrointestinal and nervous systems, while also causing psychological annoyance. Around 25% of the EU population experience a deterioration in the quality of life due to annoyance and about 5–15% suffer from sleep disorders, with many disability-adjusted life years (DALYs) lost annually. This systematic review highlights the main sources of urban noise, the relevant principal clinical disorders and the most effected countries. This review included articles published on the major databases (PubMed, Cochrane Library, Scopus), using a combination of some keywords. The online search yielded 265 references; after selection, the authors have analyzed 54 articles (5 reviews and 49 original articles). From the analysis, among the sources of exposure, we found the majority of items dealing with airports and wind turbines, followed by roads and trains; the main disorders that were investigated in different po...
International Journal of Environmental Research and Public Health, 2020
Clinical-instrumental investigations, such as electrocardiography (ECG), represent a corollary of... more Clinical-instrumental investigations, such as electrocardiography (ECG), represent a corollary of a procedures that, nowadays, is called upon as part of the principles of precision medicine. However when carrying out the professional routine examinations, most tend to ignore how a “simple” instrument can offer indispensable support in clinical practice, even in occupational medicine. The advent of the digital age, made of silicon and printed circuit boards, has allowed the miniaturization of the electronic components of these electro-medical devices. Finally, the adoption of patient wearables in medicine has been rapidly expanding worldwide for a number of years. This has been driven mainly by consumers’ demand to monitor their own health. With the ongoing research and development of new features capable of assessing and transmitting real-time biometric data, the impact of wearables on cardiovascular management has become inevitable. Despite the potential offered by this technology,...
Current Obstetrics & Gynaecology, 1997
Obstetrics & Gynecology, 1998
To investigate whether the thickness of the layers of the carotid artery (externa, media, and int... more To investigate whether the thickness of the layers of the carotid artery (externa, media, and intima) are affected by menopause and its treatment with hormone replacement therapy (HRT). Methods: One hundred twenty-nine postmenopausal women were recruited sequentially and classified into three groups. Forty-six were taking oral HRT, 32 had estradiol implants, and 51 had never taken HRT. The three layers of the externa wall of the carotid artery were identified and measured by high-resolution ultrasound. Results: Women with implants had thicker carotid artery wall measurements (0.84 ؎ ؎ ؎ 0.26 mm) than the other groups. The media (0.32 ؎ ؎ ؎ 0.11 mm) was significantly thicker in the implant group. This layer has a high connective tissue component, including collagen type I, collagen type III, and elastin fibers. The intima layer was thinner (0.25 ؎ ؎ ؎ 0.09 mm) in the oral HRT group compared with controls (0.29 ؎ ؎ ؎ 0.1 mm). A statistically significant higher intima-media ratio (1.17 ؎ ؎ ؎ 0.05) was calculated for the control group, compared with both the oral HRT (0.92 ؎ ؎ ؎ 0.04) and implant groups (0.94 ؎ ؎ ؎ 0.03). Conclusion: Our findings suggest that HRT given to postmenopausal women influences differentially the layers of the carotid artery. Hormones seem to encourage thickening of the layers with the highest connective tissue component (externa and media) and to delay thickening of the atheromatous intima layer. These effects on the vascular system may be partly responsible for the cardioprotection attributed to HRT.
The Journal of Clinical Endocrinology & Metabolism, 1998
Polycystic ovary syndrome is the most common cause of anovulatory infertility. Anovulation in pol... more Polycystic ovary syndrome is the most common cause of anovulatory infertility. Anovulation in polycystic ovary syndrome is characterized by the failure of selection of a dominant follicle with arrest of follicle development at the 5-10 mm stage. In an attempt to elucidate the mechanism of anovulation associated with this disorder we have investigated at what follicle size human granulosa cells from normal and polycystic ovaries respond to LH. Granulosa cells were isolated from individual follicles from unstimulated human ovaries and cultured in vitro in serum-free medium 199 in the presence of LH or FSH. At the end of a 48-h incubation period, estradiol (E 2) and progesterone (P) were determined in the granulosa cell-conditioned medium by RIA. In ovulatory subjects (with either normal ovaries or polycystic ovaries), granulosa cells responded to LH once follicles reached 9.5/10
The Journal of Clinical Endocrinology & Metabolism, 2007
Context: There has been renewed interest in anti-Mü llerian hormone (AMH) because of its role in ... more Context: There has been renewed interest in anti-Mü llerian hormone (AMH) because of its role in the ovary. Data on its actions are sparse, but it appears to inhibit follicle growth. Interestingly, serum AMH is two to three times higher in women with polycystic ovary (PCO) syndrome than women with normal ovaries. Objective: We examined the production of AMH by cells from a range of follicle sizes from normal ovaries and compared this with production by ovulatory and anovulatory (anov) PCOs. Design: Granulosa cells (GCs) and theca and follicular fluid (ff) were isolated from intact follicles. Cells were cultured for 48 h Ϯ FSH or LH, and AMH was measured in ff and cell-conditioned media (CM). Results: AMH levels in ff and GC-CM ranged from 42 to 2240 and 0.025 to 1.7 ng/ml, respectively, and were low or undetectable in ff and GC-CM from follicles greater than 9 mm, luteinized cells, and theca and stroma. The mean level of AMH was four times higher in GC-CM from ovulatory PCOs [mean (range) 1.56 (0.025-7)] and 75 times higher from anovPCO [21.4 (17.2-43 ng/ml)] than normal ovaries [0.37 (0.025-1.7)]. Neither LH nor FSH had an effect on AMH production by GCs from normal ovaries, but in cells from PCOs, FSH significantly decreased AMH, and in contrast, LH increased AMH. Conclusions: The reduction of AMH in follicles greater than 9 mm from normal ovaries appears to be an important requirement for the selection of the dominant follicle. AMH production per GC was 75 times higher in anovPCOs, compared with normal ovaries. This increase in AMH may contribute to failure of follicle growth and ovulation seen in polycystic ovary syndrome.
International Journal of Gynecology & Obstetrics, 2000
Objectives. Elevated levels of plasma homocysteine are an independent risk factor for coronary va... more Objectives. Elevated levels of plasma homocysteine are an independent risk factor for coronary vascular disease (CVD). An increase in plasma homocysteine of approximately 20% occurs at the menopause. Unopposed oestrogen replacement therapy in postmenopausal women reduces the serum homocysteine concentrations by up to 16.9%, an effect that appears short lived, with levels returning towards baseline over time. We investigated the effects of a new continuous combined preparation of oestradiol valerate 2 mg and norethisterone 700 ug (Climesse, Novartis) and conjugated equine oestrogen 0.625 mg with cyclical norgestrel 150 /A-g (Prempak C, Wyeth) against controls. Materials and methods. The reference population consisted of voluntary controls. Those women who chose HRT were randomised to take either Prempak C or Climesse. Sera from 53 women taking part in this study were analysed by high performance liquid chromatography for homocysteine levels at baseline and after 1, 12, and 24 months of study participation. 19 sera were from women taking Climesse, 16 taking Prempak C and 18 were from controls. Results. No significant difference in median plasma homocysteine level was observed between the treatment and control groups over the two year period. Changes from baseline in all groups were not statisically significant. There was a small non-significant reduction in homocysteine seen in both treatment groups. Plasma homocysteine levels were significantly lower in the Climesse group than the Prempak C groups at the one month and 12 month intervals, becoming non-significant at 24 months. Conclusion. The short term effects of progestogencontaining HRT in this small study appear to blunt the previously reported effects of oestrogen alone on plasma homocysteine. We have shown that Climesse may have a marginally beneficial effect when compared to Prempak Can effect that is lost over two years-as has been found with oestrogen alone. Larger randomised studies are needed to confirm this effect.
Human Reproduction, 2005
BACKGROUND: The effect of the menopause and HRT on the intervertebral discs has not been investig... more BACKGROUND: The effect of the menopause and HRT on the intervertebral discs has not been investigated. METHODS: One hundred women were recruited, comprising of 44 post-menopausal women on HRT, 33 untreated post-menopausal women and 23 pre-menopausal women. The height of the intervertebral discs between the 12th thoracic vertebra and the 3rd lumbar vertebra was measured by utilizing the bone densitometer height cursors. RESULTS: The untreated menopausal group of women had the lowest total disc height (D1-D3: 1.95 ± 0.31 cm). This was significantly lower than the pre-menopausal group D1-D3: 2.16 ± 0.24 cm) and the hormone-treated group (2.2 ± 0.26 cm) (P > 0.02). The 2nd intervertebral disc consistently maintained a significant difference between the untreated menopausal group (D2: 0.63 ± 0.13) and the other two groups (pre-menopausal group (D2: 0.72 ± 0.09 cm) and treated menopausal group (D2: 0.73 ± 0.12 cm) (P > 0.02). CONCLUSIONS: Estrogen-replete women appear to maintain higher intervertebral discs compared to untreated post-menopausal women. The estrogenic milieu may be relevant because of the significant impact it has on the hydrophilic glycosaminoglycans, the water content, collagen and elastin of the intervertebral discs. The maintenance of adequate disc height may allow the intervertebral discs to retain their discoid shape and viscoelastic function, containing vertical forces which may threaten spinal architecture leading to vertebral body compression fractures.
Fertility and Sterility, 2011
Objective: To determine that anti-M€ ullerian hormone (AMH) has been shown to inhibits E 2 produc... more Objective: To determine that anti-M€ ullerian hormone (AMH) has been shown to inhibits E 2 production in rodents and in luteinized granulosa cells (GC). We determined whether this occurs in human cells most highly expressing AMH (i.e., from small antral follicles) and whether this is an effect on aromatase promoter activity. We also investigated the effects of AMH on other factors determining FSH sensitivity. Design: Granulosa cells were exposed to AMH with and without gonadotropins for 48 hours. Setting: University laboratory. Patient(s): Not applicable. Intervention(s): None. Main Outcome Measure(s): Aromatase and FSH receptor messenger RNA expression measured using real time quantitative polymerase chain reaction (PCR). Aromatase promoter II activity measured using a luciferase assay. Estradiol, inhibin A and B, and vascular endothelial growth factor production were measured in the conditioned medium. Result(s): The AMH decreased gonadotropin-stimulated aromatase expression and decreased forskolin-stimulated aromatase in KGN cells and this effect was through a dose-dependent inhibition of promoter II. Surprisingly, AMH also reduced FSH receptor mRNA expression. High AMH doses had no effect on inhibin B, whereas a low dose stimulated production. There was no effect on inhibin A or vascular endothelial growth factor. Conclusion(s): The AMH inhibits factors affecting FSH sensitivity. As AMH levels decrease with follicle growth, this inhibition would be removed. The AMH overproduction in anovulatory polycystic ovaries (PCO) may therefore restrict folliculogenesis by an inhibitory effect on FSH sensitivity, thereby contributing to anovulation.
Fertility and Sterility, 2003
Objective: To investigate the possibility of direct effects of metformin on ovarian steroidogenes... more Objective: To investigate the possibility of direct effects of metformin on ovarian steroidogenesis. Design: Cultured ovarian cells. Setting: Academic research environment. Patient(s): Women undergoing bilateral salpingoophorectomy for benign gynecological disease. Main Outcome Measure(s): Estradiol and P were measured in granulosa cell (GC) conditioned medium and androstenedione (A) and P in theca conditioned medium. Result(s): The effect of addition of metformin alone to GCs was variable, but significant inhibition of both P and E 2 was seen (range 0%-30%). Metformin dose-dependently inhibited gonadotrophin and insulin-stimulated P and E 2 production (range 25%-50%). In theca, metformin inhibited A production (0%-40%) with no effect on P. In the presence of insulin, A was inhibited dose-dependently and P increased by a similar magnitude. Conclusion(s): These results demonstrate a direct effect of metformin on ovarian steroidogenesis. The inhibitory effects on androgen production in particular would be beneficial in polycystic ovary syndrome (PCOS).
Journal of Diabetes and its Complications, 2016
Background: Studies of the effect of type 2 diabetes (T2D) on bone mineral density (BMD have prod... more Background: Studies of the effect of type 2 diabetes (T2D) on bone mineral density (BMD have produced conflicting results, possibly due to failure to adjust for potential confounding factors. Nonetheless, T2D has consistently been associated with increased fracture risk, suggesting that other factors might play a role. Objective: This study assesses the relationship between T2D and BMD at the femoral neck and spine in diabetic and non-diabetic subjects, after adjusting for multiple covariates which may affect BMD. Intervertebral disc height was also investigated in view of its possible relation to fracture risk. Methods: A cross-sectional study of 100 patients with T2DM of at least 5 years duration and 86 non-diabetic subjects was carried out. Results: There were no significant differences in T scores in either the spine or femoral neck after adjustment for potential confounding variables between T2D subjects and controls. Diabetic patients had a statistically lower intervertebral disc height between the 2nd and 3rd lumbar vertebrae (D3) after adjustment for potential confounders (p = 0.004). Urinary albumin:creatinine ratio, total cholesterol, LDL-cholesterol and cigarette smoking were independently associated with lower height of D3 in diabetic subjects. Conclusions: There is no significant independent association between T2D and BMD. However we found a novel association of significantly lower disc height in patients with T2D. This may contribute to the increased vertebral fracture risk in subjects with T2D. Further studies are needed to investigate the relationship of disc height, T2D and fracture risk.
International Journal of Environmental Research and Public Health, 2022
The characterization of human microbiota and the impact of its modifications on the health of ind... more The characterization of human microbiota and the impact of its modifications on the health of individuals represent a current topic of great interest for the world scientific community. Scientific evidence is emerging regarding the role that microbiota has in the onset of important chronic illnesses. Since individuals spend most of their life at work, occupational exposures may have an impact on the organism’s microbiota. The purpose of this review is to explore the influence that different occupational exposures have on human microbiota in order to set a new basis for workers’ health protection and disease prevention. The literature search was performed in PubMed, Cochrane, and Scopus. A total of 5818 references emerged from the online search, and 31 articles were included in the systematic review (26 original articles and 5 reviews). Exposure to biological agents (in particular direct contact with animals) was the most occupational risk factor studied, and it was found involved in...
Backgound: Padina pavonica appears to improve the bone mineral density at the lumbar spine and at... more Backgound: Padina pavonica appears to improve the bone mineral density at the lumbar spine and at the hip in post-menopausal women (1). The aims of this project are to compare it to other treatments available on the market, for the treatment of post-menopausal osteoporosis and to shed more light on the mechanism of action of Padina pavonica. Aims and Objectives: The aim of this research-based experiment is to compare the ability of osteoblasts treated with the extract of Padina pavonica (EPP) to differentiate and fix calcium, with osteoblasts treated with raloxifene and oestradiol. Raloxifene, a selective oestrogen receptor modulator (SERM) and oestradiol in the form of hormone replacement therapy (HRT) are drugs normally used in the management of post-menopausal osteoporosis. A secondary aim is to determine whether the extract exerts its action by modulating the oestrogen receptor. This would imply that the extract of Padina pavonica has a SERM-like activity and is thus potentially...
Sustainability, 2021
The psychology of sustainability and sustainable development emphasizes the value to ensure healt... more The psychology of sustainability and sustainable development emphasizes the value to ensure health and well-being in different environments, including workplaces. Chronic exposure to noise can cause several extraordinary effects and involve all the systems of the human organism. In addition to cardiovascular, gastrointestinal, and immune effects, the data in the literature show alterations in behavioral disturbances, memory capacity, and cognitive performance. Through this systematic review, the authors try to find out the main neurobehavioral alterations in the case of occupational exposure to noise. The literature review included articles published in the major databases (PubMed, Cochrane Library, Scopus, Embase), using a combination of some relevant keywords. This online search yielded 4434 references; after selection, the authors analyzed 41 articles (4 narrative reviews and 37 original articles). From this analysis, it appears that the main symptoms are related to psychological...
International Journal of Environmental Research and Public Health, 2020
Allergic disorders in the agriculture sector are very common among farm workers, causing many inj... more Allergic disorders in the agriculture sector are very common among farm workers, causing many injuries and occupational diseases every year. Agricultural employees are exposed to multiple conditions and various allergenic substances, which could be related to onset of anaphylactic reactions. This systematic review highlights the main clinical manifestation, the allergens that are mostly involved and the main activities that are usually involved. This research includes articles published on the major databases (PubMed, Cochrane Library, Scopus), using a combination of keywords. The online search yielded 489 references; after selection, by the authors, 36 articles (nine reviews and 27 original articles) were analyzed. From this analysis, the main clinical problems that were diagnosed in this category were respiratory (ranging from rhinitis to asthma) and dermatological (eczema, dermatitis, hives) in nature, with a wide symptomatology (from a simple local reaction to anaphylaxis). The ...
International Journal of Environmental Research and Public Health, 2020
Chronic exposure to urban noise is harmful for auditory perception, cardiovascular, gastrointesti... more Chronic exposure to urban noise is harmful for auditory perception, cardiovascular, gastrointestinal and nervous systems, while also causing psychological annoyance. Around 25% of the EU population experience a deterioration in the quality of life due to annoyance and about 5–15% suffer from sleep disorders, with many disability-adjusted life years (DALYs) lost annually. This systematic review highlights the main sources of urban noise, the relevant principal clinical disorders and the most effected countries. This review included articles published on the major databases (PubMed, Cochrane Library, Scopus), using a combination of some keywords. The online search yielded 265 references; after selection, the authors have analyzed 54 articles (5 reviews and 49 original articles). From the analysis, among the sources of exposure, we found the majority of items dealing with airports and wind turbines, followed by roads and trains; the main disorders that were investigated in different po...
International Journal of Environmental Research and Public Health, 2020
Clinical-instrumental investigations, such as electrocardiography (ECG), represent a corollary of... more Clinical-instrumental investigations, such as electrocardiography (ECG), represent a corollary of a procedures that, nowadays, is called upon as part of the principles of precision medicine. However when carrying out the professional routine examinations, most tend to ignore how a “simple” instrument can offer indispensable support in clinical practice, even in occupational medicine. The advent of the digital age, made of silicon and printed circuit boards, has allowed the miniaturization of the electronic components of these electro-medical devices. Finally, the adoption of patient wearables in medicine has been rapidly expanding worldwide for a number of years. This has been driven mainly by consumers’ demand to monitor their own health. With the ongoing research and development of new features capable of assessing and transmitting real-time biometric data, the impact of wearables on cardiovascular management has become inevitable. Despite the potential offered by this technology,...
Current Obstetrics & Gynaecology, 1997
Obstetrics & Gynecology, 1998
To investigate whether the thickness of the layers of the carotid artery (externa, media, and int... more To investigate whether the thickness of the layers of the carotid artery (externa, media, and intima) are affected by menopause and its treatment with hormone replacement therapy (HRT). Methods: One hundred twenty-nine postmenopausal women were recruited sequentially and classified into three groups. Forty-six were taking oral HRT, 32 had estradiol implants, and 51 had never taken HRT. The three layers of the externa wall of the carotid artery were identified and measured by high-resolution ultrasound. Results: Women with implants had thicker carotid artery wall measurements (0.84 ؎ ؎ ؎ 0.26 mm) than the other groups. The media (0.32 ؎ ؎ ؎ 0.11 mm) was significantly thicker in the implant group. This layer has a high connective tissue component, including collagen type I, collagen type III, and elastin fibers. The intima layer was thinner (0.25 ؎ ؎ ؎ 0.09 mm) in the oral HRT group compared with controls (0.29 ؎ ؎ ؎ 0.1 mm). A statistically significant higher intima-media ratio (1.17 ؎ ؎ ؎ 0.05) was calculated for the control group, compared with both the oral HRT (0.92 ؎ ؎ ؎ 0.04) and implant groups (0.94 ؎ ؎ ؎ 0.03). Conclusion: Our findings suggest that HRT given to postmenopausal women influences differentially the layers of the carotid artery. Hormones seem to encourage thickening of the layers with the highest connective tissue component (externa and media) and to delay thickening of the atheromatous intima layer. These effects on the vascular system may be partly responsible for the cardioprotection attributed to HRT.
The Journal of Clinical Endocrinology & Metabolism, 1998
Polycystic ovary syndrome is the most common cause of anovulatory infertility. Anovulation in pol... more Polycystic ovary syndrome is the most common cause of anovulatory infertility. Anovulation in polycystic ovary syndrome is characterized by the failure of selection of a dominant follicle with arrest of follicle development at the 5-10 mm stage. In an attempt to elucidate the mechanism of anovulation associated with this disorder we have investigated at what follicle size human granulosa cells from normal and polycystic ovaries respond to LH. Granulosa cells were isolated from individual follicles from unstimulated human ovaries and cultured in vitro in serum-free medium 199 in the presence of LH or FSH. At the end of a 48-h incubation period, estradiol (E 2) and progesterone (P) were determined in the granulosa cell-conditioned medium by RIA. In ovulatory subjects (with either normal ovaries or polycystic ovaries), granulosa cells responded to LH once follicles reached 9.5/10
The Journal of Clinical Endocrinology & Metabolism, 2007
Context: There has been renewed interest in anti-Mü llerian hormone (AMH) because of its role in ... more Context: There has been renewed interest in anti-Mü llerian hormone (AMH) because of its role in the ovary. Data on its actions are sparse, but it appears to inhibit follicle growth. Interestingly, serum AMH is two to three times higher in women with polycystic ovary (PCO) syndrome than women with normal ovaries. Objective: We examined the production of AMH by cells from a range of follicle sizes from normal ovaries and compared this with production by ovulatory and anovulatory (anov) PCOs. Design: Granulosa cells (GCs) and theca and follicular fluid (ff) were isolated from intact follicles. Cells were cultured for 48 h Ϯ FSH or LH, and AMH was measured in ff and cell-conditioned media (CM). Results: AMH levels in ff and GC-CM ranged from 42 to 2240 and 0.025 to 1.7 ng/ml, respectively, and were low or undetectable in ff and GC-CM from follicles greater than 9 mm, luteinized cells, and theca and stroma. The mean level of AMH was four times higher in GC-CM from ovulatory PCOs [mean (range) 1.56 (0.025-7)] and 75 times higher from anovPCO [21.4 (17.2-43 ng/ml)] than normal ovaries [0.37 (0.025-1.7)]. Neither LH nor FSH had an effect on AMH production by GCs from normal ovaries, but in cells from PCOs, FSH significantly decreased AMH, and in contrast, LH increased AMH. Conclusions: The reduction of AMH in follicles greater than 9 mm from normal ovaries appears to be an important requirement for the selection of the dominant follicle. AMH production per GC was 75 times higher in anovPCOs, compared with normal ovaries. This increase in AMH may contribute to failure of follicle growth and ovulation seen in polycystic ovary syndrome.
International Journal of Gynecology & Obstetrics, 2000
Objectives. Elevated levels of plasma homocysteine are an independent risk factor for coronary va... more Objectives. Elevated levels of plasma homocysteine are an independent risk factor for coronary vascular disease (CVD). An increase in plasma homocysteine of approximately 20% occurs at the menopause. Unopposed oestrogen replacement therapy in postmenopausal women reduces the serum homocysteine concentrations by up to 16.9%, an effect that appears short lived, with levels returning towards baseline over time. We investigated the effects of a new continuous combined preparation of oestradiol valerate 2 mg and norethisterone 700 ug (Climesse, Novartis) and conjugated equine oestrogen 0.625 mg with cyclical norgestrel 150 /A-g (Prempak C, Wyeth) against controls. Materials and methods. The reference population consisted of voluntary controls. Those women who chose HRT were randomised to take either Prempak C or Climesse. Sera from 53 women taking part in this study were analysed by high performance liquid chromatography for homocysteine levels at baseline and after 1, 12, and 24 months of study participation. 19 sera were from women taking Climesse, 16 taking Prempak C and 18 were from controls. Results. No significant difference in median plasma homocysteine level was observed between the treatment and control groups over the two year period. Changes from baseline in all groups were not statisically significant. There was a small non-significant reduction in homocysteine seen in both treatment groups. Plasma homocysteine levels were significantly lower in the Climesse group than the Prempak C groups at the one month and 12 month intervals, becoming non-significant at 24 months. Conclusion. The short term effects of progestogencontaining HRT in this small study appear to blunt the previously reported effects of oestrogen alone on plasma homocysteine. We have shown that Climesse may have a marginally beneficial effect when compared to Prempak Can effect that is lost over two years-as has been found with oestrogen alone. Larger randomised studies are needed to confirm this effect.
Human Reproduction, 2005
BACKGROUND: The effect of the menopause and HRT on the intervertebral discs has not been investig... more BACKGROUND: The effect of the menopause and HRT on the intervertebral discs has not been investigated. METHODS: One hundred women were recruited, comprising of 44 post-menopausal women on HRT, 33 untreated post-menopausal women and 23 pre-menopausal women. The height of the intervertebral discs between the 12th thoracic vertebra and the 3rd lumbar vertebra was measured by utilizing the bone densitometer height cursors. RESULTS: The untreated menopausal group of women had the lowest total disc height (D1-D3: 1.95 ± 0.31 cm). This was significantly lower than the pre-menopausal group D1-D3: 2.16 ± 0.24 cm) and the hormone-treated group (2.2 ± 0.26 cm) (P > 0.02). The 2nd intervertebral disc consistently maintained a significant difference between the untreated menopausal group (D2: 0.63 ± 0.13) and the other two groups (pre-menopausal group (D2: 0.72 ± 0.09 cm) and treated menopausal group (D2: 0.73 ± 0.12 cm) (P > 0.02). CONCLUSIONS: Estrogen-replete women appear to maintain higher intervertebral discs compared to untreated post-menopausal women. The estrogenic milieu may be relevant because of the significant impact it has on the hydrophilic glycosaminoglycans, the water content, collagen and elastin of the intervertebral discs. The maintenance of adequate disc height may allow the intervertebral discs to retain their discoid shape and viscoelastic function, containing vertical forces which may threaten spinal architecture leading to vertebral body compression fractures.
Fertility and Sterility, 2011
Objective: To determine that anti-M€ ullerian hormone (AMH) has been shown to inhibits E 2 produc... more Objective: To determine that anti-M€ ullerian hormone (AMH) has been shown to inhibits E 2 production in rodents and in luteinized granulosa cells (GC). We determined whether this occurs in human cells most highly expressing AMH (i.e., from small antral follicles) and whether this is an effect on aromatase promoter activity. We also investigated the effects of AMH on other factors determining FSH sensitivity. Design: Granulosa cells were exposed to AMH with and without gonadotropins for 48 hours. Setting: University laboratory. Patient(s): Not applicable. Intervention(s): None. Main Outcome Measure(s): Aromatase and FSH receptor messenger RNA expression measured using real time quantitative polymerase chain reaction (PCR). Aromatase promoter II activity measured using a luciferase assay. Estradiol, inhibin A and B, and vascular endothelial growth factor production were measured in the conditioned medium. Result(s): The AMH decreased gonadotropin-stimulated aromatase expression and decreased forskolin-stimulated aromatase in KGN cells and this effect was through a dose-dependent inhibition of promoter II. Surprisingly, AMH also reduced FSH receptor mRNA expression. High AMH doses had no effect on inhibin B, whereas a low dose stimulated production. There was no effect on inhibin A or vascular endothelial growth factor. Conclusion(s): The AMH inhibits factors affecting FSH sensitivity. As AMH levels decrease with follicle growth, this inhibition would be removed. The AMH overproduction in anovulatory polycystic ovaries (PCO) may therefore restrict folliculogenesis by an inhibitory effect on FSH sensitivity, thereby contributing to anovulation.
Fertility and Sterility, 2003
Objective: To investigate the possibility of direct effects of metformin on ovarian steroidogenes... more Objective: To investigate the possibility of direct effects of metformin on ovarian steroidogenesis. Design: Cultured ovarian cells. Setting: Academic research environment. Patient(s): Women undergoing bilateral salpingoophorectomy for benign gynecological disease. Main Outcome Measure(s): Estradiol and P were measured in granulosa cell (GC) conditioned medium and androstenedione (A) and P in theca conditioned medium. Result(s): The effect of addition of metformin alone to GCs was variable, but significant inhibition of both P and E 2 was seen (range 0%-30%). Metformin dose-dependently inhibited gonadotrophin and insulin-stimulated P and E 2 production (range 25%-50%). In theca, metformin inhibited A production (0%-40%) with no effect on P. In the presence of insulin, A was inhibited dose-dependently and P increased by a similar magnitude. Conclusion(s): These results demonstrate a direct effect of metformin on ovarian steroidogenesis. The inhibitory effects on androgen production in particular would be beneficial in polycystic ovary syndrome (PCOS).