Dydrogesterone and norethisterone regulate expression of lipoprotein lipase and hormone-sensitive lipase in human subcutaneous abdominal adipocytes.

AIM: In premenopausal women, hyperandrogenicity is associated with central obesity and an increased cardiovascular risk. The aim of this study was to investigate the effects of dydrogesterone (DYD) (a non-androgenic progestogen) and norethisterone (NET) (an androgenic progestogen) on lipoprotein lipase (LPL), hormone-sensitive lipase (HSL) and glycerol release in adipocytes isolated from subcutaneous abdominal adipose tissue. METHODS: Adipose tissue was obtained from 12 non-diabetic women, mean age 51 years (range 37-78) and mean body mass index 25.4 kg/m(2) (range 20.3-26.4). Adipocytes were treated with increasing doses of DYD and NET for 48 h prior to protein extraction. Effects on lipogenesis and lipolysis were assessed using western blotting to determine the expression of key enzymes, LPL (56 kDa) and HSL (84 kDa) respectively. Measurement of glycerol release into the medium provided an assessment of lipolytic activity. RESULTS: Expression of LPL was increased by DYD and NET (mean protein expression relative to control +/- s.e.), with greatest effect at 10(-8) M for DYD: 2.32 +/- 0.51 (p < 0.01) and 10(-8) M for NET: 2.06 +/- 0.19 (p < 0.01). In contrast, HSL expression was reduced by all concentrations of DYD, with maximal effect at 10(-9) M : 0.49 +/- 0.02 (p < 0.001). NET reduced HSL expression at all concentrations from 10(-9) M : 0.62 +/- 0.06 (p < 0.001) to 10(-7) M : 0.69 +/- 0.08 (p < 0.001). Glycerol measurements supported the HSL expression studies although they were not statistically significant (p > 0.05). CONCLUSIONS: DYD and NET significantly increased LPL expression relative to control, while significantly reducing HSL expression. At the concentrations studied, similar effects were observed with the androgenic NET and the non-androgenic DYD despite differing effects on the lipid profile when taken orally in combination with oestrogen. Further work examining the effects of different progestogens on body fat distribution may enable progestogen use to be tailored to maximize benefits and minimize potential harm.

Menopausal symptoms in women treated for breast cancer: the prevalence and severity of symptoms and their perceived effects on quality of life.

OBJECTIVES: To determine, first, the prevalence and severity of various symptoms related to estrogen deficiency in women within a few years of receiving treatment for breast cancer, second, how women perceive the effects of these symptoms on their quality of life and, third, what measures have been taken to relieve vasomotor symptoms. METHODS: Two hundred women (aged 29-65 years) who had received treatment for breast cancer within the last 5 years were included in this cross-sectional survey. Information was collected about their breast cancer treatment, menopausal symptoms (Menopausal Rating Scale), the perceived effects of menopausal symptoms on their and their partner's quality of life and any treatments they were receiving for hot flushes. RESULTS: All but one woman reported at least one symptom related to the menopause (95.9% vasomotor; 83.3% psychological; 89.7% somatic). Current treatment with tamoxifen or previous chemotherapy did not influence the prevalence or the severity of hot flushes. Current antidepressant treatment was, however, significantly associated with a higher prevalence and severity of most menopausal symptoms, including hot flushes and sweats (p = 0.008). The severity of hot flushes and sweats was significantly correlated with self-assessed effects on overall quality of life (r(s) = 0.47); 56.4% of the respondents believed that menopausal symptoms had affected their partner's quality of life, the strongest correlations being with severity of sexual symptoms (r(s) = 0.56) and vaginal dryness (r(s) = 0.5). Only 21% of women experiencing hot flushes were receiving any treatment for hot flushes, with most women describing no knowledge or poor knowledge of treatment options. CONCLUSIONS: The majority of women receiving treatment for breast cancer report menopausal symptoms, which negatively correlate, not only with their own, but also with their partner's quality of life. Most women experiencing hot flushes are not receiving treatment due to lack of both awareness and confidence in the existing treatment options.

17Beta-estradiol and anti-estrogen ICI:compound 182,780 regulate expression of lipoprotein lipase and hormone-sensitive lipase in isolated subcutaneous abdominal adipocytes.

We sought to investigate the influence of 17beta-estradiol (E(2)) on key enzymes of lipogenesis and lipolysis in subcutaneous (SC) abdominal adipocytes isolated from women. In addition, we wished to determine the influence of an anti-estrogen, ICI:compound 182,780 (anti-E), known to act via the estrogen receptor (ER), alone and in combination with E(2). Adipose tissue was obtained from 17 women undergoing elective surgery, with a mean age of 47 years (range, 34 to 62), mean weight of 65.4 kg (range, 58.1 to 75.0), and mean body mass index (BMI) of 25 kg/m(2) (range, 22 to 27). Isolated adipocytes were treated with varying doses of E(2), anti-E, or E(2) in combination with anti-E 10(-8) mol/L for 48 hours. Following treatment, proteins were extracted and the effects on lipogenesis and lipolysis were assessed, using Western blotting to determine the relative expression of the key enzymes of these processes, lipoprotein lipase (LPL; 56 kd), and hormone-sensitive lipase (HSL; 84 kd), respectively. Glycerol release into the medium was also measured as an index of lipolytic activity. The protein expression studies demonstrated that E(2) altered expression of LPL relative to control, with the highest dose significantly reducing LPL expression and the lower doses significantly increasing LPL expression (mean protein expression relative to control +/- SE): E(2) 10(-12) mol/L, 1.79 +/- 0.16 (P <.001); E(2) 10(-7) mol/L, 0.56 +/- 0.08 (P <.05). In contrast, HSL expression was increased relative to control at the higher doses of E(2) but was not significantly altered relative to control at the lower doses: E(2) 10(-12) mol/L, 1.02 +/- 0.14 (P >.05); E(2) 10(-7) mol/L, 1.55 +/- 0.17 (P <.01). Anti-E 10(-8) mol/L alone reduced LPL protein expression relative to control (P <.05) and increased HSL protein expression relative to control (P >.05). In combination with E(2) 10(-7) mol/L, anti-E 10(-8) mol/L did not abrogate the inhibitory effect on LPL expression relative to control (P <.05). Furthermore, E(2) 10(-7) mol/Lin combination with anti-E 10(-8) mol/L, displayed a stimulatory effect on HSL expression relative to control (P <.01). Glycerol release studies following the higher doses of E(2), and also following E(2) 10(-7) mol/L in combination with anti-E 10(-8) mol/L, provided support for the HSL protein expression studies. We conclude that the highest concentration of E(2) (10(-7) mol/L) significantly reduced LPL expression relative to control, while the lower concentrations significantly increased LPL expression relative to control. The highest concentration of E(2) also significantly increased both HSL expression and glycerol release relative to control. The effects of anti-E suggest that the in vitro effects of E(2) on lipogenesis and lipolysis occur, at least in part, through a receptor-mediated pathway. In addition, as recently observed in other tissues, ICI:compound 182,780 does not appear to behave as a pure anti-estrogen in isolated human adipocytes.

HRT in women with diabetes--review of the effects on glucose and lipid metabolism.

Hormone replacement therapy (HRT) is prescribed less frequently to women with diabetes. In this article, we review the effects of HRT on glucose metabolism and plasma lipids in women with type 2 diabetes. Current evidence is reassuring about the effects of HRT in women with diabetes, although as in all women, HRT should be prescribed on an individual basis with appropriate consideration given to advantages and disadvantages of therapy.

Hormone replacement therapy for postmenopausal women with diabetes.

BACKGROUND: Recent studies have shown only 17% of postmenopausal women in the UK receive prescriptions for hormone replacement therapy (HRT), with diabetic women being prescribed HRT 30% less often than non-diabetic women. Up to 80% of women experience menopausal symptoms, however, so it is expected that by using HRT many would gain benefit from symptom relief, in addition to benefiting from its effects in disease prophylaxis. METHODS: We conducted a questionnaire survey of the attitudes to HRT prescribing of 178 local general practitioners (GPs) and 47 hospital doctors, working in diabetes and gynaecology. RESULTS: Responses were received from 98 (55%) GPs and 39 (83%) hospital doctors. One hundred and thirty-six (99%) would advise HRT for menopausal symptoms, with 133 (97%) advising HRT for a spontaneous premature menopause and 126 (92%) for a surgically induced menopause. One hundred and thirty-four (98%) would advise HRT for diabetic women with menopausal symptoms, with 122 (89%) indicating that HRT had no adverse effect on glycaemic control. For disease prophylaxis, all hospital doctors and 93 (95%) GPs would advise HRT for prevention of osteoporosis, although only 91 (93%) GPs would advise HRT to diabetic women for this indication. Thirty-three (85%) hospital doctors would advise HRT as prophylaxis against cardiovascular disease compared with 66 (67%) of GPs. For this indication in diabetic women, 32 (82%) hospital doctors and 67 (68%) GPs would advise HRT. Oral HRT was the most widely recommended preparation although GPs also frequently recommended patches. Topical gel, implants and other preparations were less commonly advised. Hospital doctors predominantly advised HRT for menopausal symptoms to be continued for between 1 and 5 years, although more GPs recommended HRT to be continued for longer than 5 years. The majority of doctors from both groups advised that HRT used for disease prophylaxis be continued for more than 5 years. CONCLUSION: More doctors than anticipated indicated they would recommend HRT, especially to diabetic women. Concerns among doctors about the side-effects of HRT and, in particular, the metabolic effects of HRT, do not appear to deter them from advising HRT. Willingness to prescribe a drug, however, is different from actually prescribing it and responses to questionnaires tend to be those regarded as being acceptable. Low patient demand for HRT due to fear or lack of awareness may also be contributing. Organizational change with the development of more menopause clinics may facilitate wider use of HRT.

Does classical music damage the hearing of musicians? A review of the literature.

Hearing losses resulting from noise exposure have been described for over 150 years. Studies looking at the effect music might have on hearing began more recently in the 1960s. Such work has established a firm association between live rock and roll music and hearing loss in musicians. However, the evidence that classical music may damage the hearing of musicians remains conflicting. This paper reviews the published literature.