Agreement between patient global impression scale of improvement, pelvic floor distress inventory and 15D in measuring the outcome of pelvic organ prolapse surgery.

AIMS: To evaluate the correlation between three commonly used patient-reported outcome measures, two generic and one condition-specific instrument, in assessing the change in health-related quality of life following pelvic organ prolapse surgery. METHODS: The generic health-related quality of life measure 15-dimensional instrument (15D), Patient Global Impression of Improvement (PGI-I), and prolapse-specific Pelvic Floor Distress Inventory (PDFI-20) were used to assess the effectiveness of pelvic organ prolapse surgery in the national FINPOP study of 3535 surgeries (83% of all pelvic organ prolapse operations) performed in Finland in 2015. Spearman correlations between PGI-I, change in 15D and its dimensions and change in PFDI-20 and its subscales over a 2-year follow-up were investigated. The proportion of concordant ratings was also studied by investigating the proportion of women rated similarly (worse/no change/better/much better) by two instruments according to validated cutoffs. RESULTS: Among 2248 women for whom the 2-year change in all instruments could be measured, changes in PFDI-20 and 15D and its dimensions were weak (ρ < 0.2 for all except excretion; ρ = 0.39 and sexual activity; ρ = 0.27). PFDI-20 change (ρ = 0.39) and its subscales (ρ = 0.19-0.40, all P < .001) were more strongly correlated with PGI-I. The proportion of fully concordant ratings were higher for PFDI-20 and PGI-I (50.6%) than for PFDI-20 and 15D (33.0%). CONCLUSION: The weak correlations between 15D, PGI-I, and PDFI-20 observed in this study show that the quantified health gains are strongly dependent on the chosen patient-reported outcome measures. This demonstrates the importance of using condition-specific sensitive outcome measures in assessing the impact of surgical treatment in pelvic organ prolapse.

Pelvic organ prolapse surgery and quality of life-a nationwide cohort study.

BACKGROUND: Patient satisfaction and health-related quality of life are nowadays considered as the most important outcomes of pelvic organ prolapse treatment, and large, prospective clinical studies reporting the patient-reported surgical outcomes are needed. OBJECTIVE: To evaluate the effect of female pelvic organ prolapse surgery on health-related quality of life and patient satisfaction and to determine predictors of outcome. STUDY DESIGN: This prospective nationwide cohort study consisted of 3515 women undergoing surgery for pelvic organ prolapse in 2015. The outcomes were measured by validated health-related quality of life instruments (generic 15D, Pelvic Floor Distress Inventory-20, and Patient Global Impression of Improvement) at 6 months and 2 years postoperatively. The baseline predictors of outcomes were studied with logistic regression analysis. RESULTS: In total, 2528 (72%) women were eligible for analysis at 6 months and 2351 (67%) at 2 years. The mean change in the total 15D score suggested a clinically important improvement at 6 months but not at 2 years. However, an improvement in sexual activity, discomfort and symptoms, and excretion was observed during both follow-up assessments. Altogether, 77% and 72% of the participants reported a clinically significant improvement in Pelvic Floor Distress Inventory-20 at the 6-month and 2-year follow-ups, respectively. A total of 84% were satisfied with the outcome and 90% reported an improvement in comparison with the preoperative state with Patient Global Impression of Improvement-I. The strongest predictive factors for a favorable outcome were advanced apical prolapse (adjusted odds ratio, 2.06; 95% confidence interval, 1.58-2.70) and vaginal bulge (1.90, 1.30-2.80). Smoking was associated with an unfavorable outcome as measured by Patient Global Index of Improvement-I (1.69, 1.02-2.81). CONCLUSION: Pelvic organ prolapse surgery improved health-related quality of life in 7 of 10 patients over a 2-year follow-up period, and patient satisfaction was high. Apical prolapse beyond the hymen and vaginal bulge were the most consistent predictors for improvement. Our results suggest that patients should be encouraged to stop smoking to avoid an unfavorable outcome.

Methods of surgery for pelvic organ prolapse in a nationwide cohort (FINPOP 2015).

INTRODUCTION: The management of pelvic organ prolapse (POP) varies significantly between countries. The objective of this study was to describe the methods used for POP surgery in Finland and to identify the factors that affect clinicians' choice to use either a native tissue repair (NTR) or a mesh repair method. MATERIAL AND METHODS: This prospective cohort study included 3535 surgeries covering 83% of all POP operations performed in Finland in 2015. The operative details and patient characteristics, including the Pelvic Floor Distress Inventory (PFDI-20), were compared between three selected surgical methods: NTR, transvaginal mesh (TVM) and abdominal mesh (AM). The predictive factors for the use of mesh augmentation were also studied with logistic regression analysis. RESULTS: The most common method was NTR (n = 2855, 81%), followed by TVM (n = 429, 12%) and AM (n = 251, 7%). Approximately 92% of the patients who underwent primary prolapse surgery underwent NTR, and mesh surgery was used mainly for recurrent prolapse. The strongest predictor of mesh surgery was previous POP surgery for the same vaginal compartment (adjusted odds ratio [OR] = 56, 95% confidence interval [CI] = 38-84 for TVM; adjusted OR = 22, 95% CI = 14-34 for AM). Other predictive factors for mesh surgery were previous hysterectomy, healthcare district, severe bulge symptoms and advanced prolapse. TVM was associated with advanced anterior prolapse and older age. AM surgery was associated with advanced apical and/or posterior compartment prolapse. PFDI-20 scores were the highest in the AM group (108 vs 103 in the TVM group and 98 in the NTR group, P = 0.012), which indicates more bothersome symptoms than in the other groups. CONCLUSIONS: The Finnish practices follow international guidelines that advocate NTR as the principal surgical method for POP. Synthetic mesh augmentation was mainly used in patients with recurrent and advanced prolapse with severe symptoms. The variation in the rates of mesh augmentation for POP surgery in different hospitals implies a lack of sufficient evidence of the most suitable treatment method and indicates a need for national guidelines.

Validation of the short forms of the Pelvic Floor Distress Inventory (PFDI-20), Pelvic Floor Impact Questionnaire (PFIQ-7), and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) in Finnish.

BACKGROUND: Although several validated generic health-related quality of life instruments exist, disease-specific instruments are important as they are often more sensitive to changes in symptom severity. It is essential to validate the instruments in a new population and language before their use. The objective of the study was to translate into Finnish the short forms of three condition-specific questionnaires (PFDI-20, PFIQ-7 and PISQ-12) and to evaluate their psychometric properties in Finnish women with symptomatic pelvic organ prolapse. METHODS: A multistep translation method was used followed by an evaluation of validity and reliability in prolapse patients. Convergent and discriminant validity, internal consistency and reliability via test-retest were calculated. RESULTS: Sixty-three patients waiting for prolapse surgery filled the three questionnaires within two weeks. Response rate for each item was high in PFDI-20 and PISQ-12 (99.8 and 98.9% respectively). For PFIQ-7 response rate was only 60%. In PFIQ-7, six respondents (9.5%) reached the minimum value of zero showing floor effect. None of the instruments had ceiling effect. Based on the item-total correlations both PFIQ-7 and PFDI-20 had acceptable convergent validity, while the convergent validity of PISQ-12 was lower, r = 0.138-0.711. However, in this instrument only three questions (questions 6, 10 and 11) had r < 0.3 while others had r ≥ 0.380. In the test-retest analysis all the three instruments showed good reliability (ICC 0.75-0.92). Similarly, the internal consistency of the instruments, measured by Cronbach's α, was good (range 0.69-0.96) indicating high homogeneity. CONCLUSIONS: Finnish validated translation of the PFDI-20 and PISQ-12 have acceptable psychometric properties and can be used for both research purposes and clinical evaluation of pelvic organ prolapse symptoms. The Finnish version of PFIQ-7 displayed low response rate and some evidence of a floor effect, and thus its use is not recommended in its current form.

Risk of Alzheimer's disease among users of postmenopausal hormone therapy: A nationwide case-control study.

OBJECTIVE: To examine the association between postmenopausal hormone therapy (HT) and Alzheimer's disease (AD). METHODS: Medicine and Alzheimer's disease (MEDALZ) is a nested case-control study of the entire Finnish population with clinically verified AD from 2005 to 2011 and up to 4 matched controls per case. This study comprises 230,580 women (46,117 cases and 184,463 controls). Data on HT use from 1995 to 2011 was extracted from the national prescription register using following ATC codes: G03C (estrogen), G03D (progestogen) and G03F (estrogen and progestogen in combination). Only systemic HT (oral or transdermal) was considered. RESULTS: Use of systemic estrogen and progestogen was associated with an increased risk of AD, with ORs (95% CI) of 1.10 (1.06-1.12) and 1.13 (1.10-1.17) respectively, but use of systemic estrogen HT for >10years (OR, 95% CI: 0.91, 0.84-0.99) was protective against AD. Long-term (>10years) use of progestogen and combination HT was not related to AD risk (OR, 95% CI: 1.0, 0.90-1.2). CONCLUSION: Our findings do not suggest HT is an important determinant of AD risk.

Hysterectomies in Finland in 1990-2012: comparison of outcomes between trainees and specialists.

OBJECTIVE: To assess trends for hysterectomy methods in the Nordic countries and to compare outcomes of hysterectomies in Finland done by trainees with those done by specialists. DESIGN: Register-based study. SETTING: NOMESCO database for the Nordic countries and the Finnish Hospital Discharge Register. POPULATION: National prospective cohort of 5279 hysterectomies in Finland. METHODS: Numbers of hysterectomies in the Nordic countries were collected in 1995-2011 and in Finland in 1990-2012. The Finhyst study to collect data on hysterectomies for benign indications was carried out in Finland in 2006. Information concerning patients, surgeons, and hysterectomy outcome was analysed. MAIN OUTCOME MEASURES: Hysterectomy numbers and methods. Operating time, blood loss, and complications in hysterectomies done by trainees and specialists. RESULTS: In Finland, the rate of hysterectomies has been reduced by approximately 50% since the 1990s and is now similar to that in the other Nordic countries. The laparoscopic method is twice as common in Finland as in other Nordic countries, constituting 35-40% of all hysterectomies. The operating time for all hysterectomy methods was 16-25% longer among trainees than specialists. For the abdominal or laparoscopic methods there were no significant differences in the complication rates between the groups. In the vaginal approach, blood loss of ≥1000 mL was slightly more common in operations done by trainees (1.3% vs. 2.6%, p = 0.037). CONCLUSIONS: Laparoscopic hysterectomy is more common in Finland than in the other Nordic countries. Although trainees need more time to operate, there were no differences between the trainees and the specialists with regard to major complication rates.

From systemic hormone therapy to vaginal estrogen - a nationwide register study in Finland, 2003-2012.

OBJECTIVES: To assess the patterns of use of reimbursed systemic hormone therapy (HT) and vaginal estrogen preparations among women aged 45 and older in Finland. STUDY DESIGN: Reimbursed purchases of prescribed systemic HT and vaginal estrogen preparations for the years 2003-2012 were obtained from a nationwide prescription registry. Systemic preparations included estrogen patches, gels and tablets, tibolone, continuous combination preparations and sequential combination preparations. Prescribed vaginal estrogens included a vaginal ring and vaginal tablets. MAIN OUTCOME MEASURES: Annual period prevalence for systemic HT and vaginal estrogen use. RESULTS: The total prevalence of prescribed HT use remained relatively constant (at 26-27%) throughout the studied period, but the share of women using systemic preparations decreased from 21% to 12%, while the share of women using vaginal estrogens increased from 9% to 19%. Decreases were observed for all classes of systemic preparations, although the decrease was largest for sequential combination preparations (from 4.9% to 1.6%) and estrogen tablets (from 5.2% to 2.9%). Continuous combination preparations remained the most commonly used types of systemic preparation (5.4-4.2%). Systemic HT use decreased most among 45-49 year old women (9.5-4.3%), while the use of vaginal estrogens increased most among those aged 65 and over. CONCLUSIONS: Based on the register data, the trends in HT use indicate changed prescribing patterns in accordance with clinical guidelines. It is notable that since 2009, vaginal estrogen was more commonly prescribed than systemic HT.

Ten years of progress--improved hysterectomy outcomes in Finland 1996-2006: a longitudinal observation study.

OBJECTIVES: To study the outcome of various hysterectomies in 2 years 1996 (N =10110) and 2006 (N=5279). The hypothesis was that the change in operative practices in 10 years has resulted in improvements. DESIGN: 2 prospective nationwide cohort evaluations with the same questionnaire. SETTING: All national operative hospitals in Finland. PARTICIPANTS: Patients scheduled to either abdominal hysterectomy (AH), vaginal hysterectomy (VH) or laparoscopic hysterectomy (LH) for benign disease. OUTCOME MEASURES: Patients' characteristics, surgery-related details and complications (organ injury, infection, venous thromboembolism and haemorrhage). RESULTS: The overall complication rates fell in LH and markedly in VH (from 22.2% to 11.7%, p<0.001). The overall surgery-related infectious morbidity decreased in all groups and significantly in VH (from 12.3% to 5.2%, p<0.001) and AH (from 9.9% to 7.7%, p<0.05). The incidence of bowel lesions in VH sank from 0.5% to 0.1% and of ureter lesions in LH from 1.1% to 0.3%. In 2006 there were no deaths compared with three in 1996. CONCLUSIONS: The rate of postoperative complications fell markedly in the decade from 1996 to 2006. This parallels with the recommendation of the recent meta-analyses by Cochrane collaboration; the order of preference of hysterectomies was for the first time precisely followed in this nationwide study. TRIAL REGISTRATION: The 2006 study was registered in the Clinical Trials of Protocol Registration System Data (NCT00744172).

[Current treatment of endometriosis]. / Endometrioosin nykyhoito.

Early diagnosis of endometriosis is important for proper planning of the treatment. First-line treatment of moderate endometriosis is hormonal drug therapy, which should be long-standing. Surgery is needed, if pain symptoms cannot be controlled with medication. For patients with severe endometriosis, surgical treatment is often the first-line therapy. Complete elimination of the foci of endometriosis is attempted already at the first time. More than half of endometriosis patients will get pregnant and give birth to a child either naturally or via infertility treatments.

Menopausal hormone therapy--benefits, adverse reactions, concerns and information sources in 2009.

OBJECTIVES: The aim of this study was to examine hormone therapy (HT) users' experiences, perceptions and information sources in 2009. STUDY DESIGN: Questionnaire survey was conducted in 2009 among women using HT. The questionnaire (n=500) was distributed from pharmacies across Finland. The response rate was 58% (n=281). MAIN OUTCOME MEASURES: The survey measured self-reported benefits and adverse reactions, fears and information sources. RESULTS: The number of systemic HT users reporting fears was 50% (n=99). The most common fear was breast cancer (27%). Systemic HT users who had considered discontinuation of HT or had temporarily discontinued HT experienced fears more often than other respondents (p<0.001 and p=0.029). The most common source of information on the benefits of HT in both surveys was a physician (91%), whereas the most common source of information on adverse reactions was the media (54%). Vaginal HT users had experienced similar fears as users of systemic HT. CONCLUSIONS: Women using HT need more information about the risks of HT from their physician. This is especially important for women who are not able to manage the symptoms without HT, but have tried or considered discontinuation and for vaginal HT users.

FINHYST, a prospective study of 5279 hysterectomies: complications and their risk factors.

BACKGROUND: Hysterectomy guidelines highlight an increase in urinary tract injuries with laparoscopic hysterectomy (LH). This national survey analyses complications of LH, abdominal hysterectomy (AH) and vaginal hysterectomy (VH). METHODS: A prospective cohort undergoing hysterectomy for benign indications during 2006 was drawn from 53 hospitals in Finland; all communal hospitals participated. Detailed questionnaires covered surgical data and intra- and post-operative major and minor complications, for which risk factors were analysed by a multivariate logistic regression model adjusted for surgical data and patient characteristics. RESULTS: Major complications rates in AH (n= 1255, 24%), LH (1679, 32%) and VH (2345, 44%) were 4.0, 4.3 and 2.6%, and total complications rates were 19.2, 15.4 and 11.7%, respectively. Logistic regression showed no statistically significant differences between approaches for any organ injuries or other major complications. Most bladder and bowel injuries (88 and 83%), but not ureter injuries (10%), were recognized intra-operatively. The ureter injury rate was low after LH (0.3%), as it was after other types of hysterectomy. Compared with LH, AH increased the odds of wound infection, and was an independent risk factor for urinary infections and febrile events. Compared with AH, LH and VH both presented a higher risk for pelvic infection; surgically treated equally often regardless of the type of hysterectomy. No differences in complications emerged between LH and VH. Obesity was a risk factor for many infections. Surgical adhesiolysis [odds ratio (OR) 2.41, 95% confidence interval (CI) 1.38-4.21] was the strongest single risk factor for major complications as a whole. Bladder injury was associated with a history of caesarean section (OR 4.01, 95% CI 2.06-7.83) and with a large uterus ≥500 g (OR 2.88, 95% CI 1.05-7.90), while bowel injury was associated with adhesiolysis (OR 29.07, 95% CI 7.17-117.88). CONCLUSIONS: FINHYST is a large prospective hysterectomy study illustrating actual complications. Whenever possible, hysterectomy should be minimally invasive.

Information sources used by women in Finland who use hormonal contraceptives.

OBJECTIVE: The aim of this study was to examine information sources used by women who use hormonal contraceptives (HCs), and how information source affected women's attitudes and perceptions in 2001 and 2007. SETTING: The questionnaires were distributed from university pharmacies in 12 large cities across Finland. METHOD: The data were collected with two questionnaire surveys among women who used hormonal contraceptives in 2001 and 2007. In the 2001 survey the response rate was 53% (n = 264) and in the 2007 survey 55% (n = 436). RESULTS: The number of respondents who considered professional information sources the most important information sources was markedly bigger in 2007 than in 2001 (P = 0.005). The most common source of information concerning the benefits of hormonal contraceptives was a physician (2001: 43%, 2007: 53%). The most common source of information concerning the risks of hormonal contraceptives was friends and relatives (43%) in 2001 and physician in 2007 (35%). Only a few percent of the respondents considered a pharmacy the most important information source both the 2001 and 2007 surveys. CONCLUSION: The importance of health care professionals as sources of information concerning hormonal contraceptives has increased. However, role of pharmacists as information source was surprisingly small. Women who use hormonal contraceptives need more information from professional sources to alleviate possible fears associated with use.

FINHYST 2006--national prospective 1-year survey of 5,279 hysterectomies.

BACKGROUND: In Finland, the number of hysterectomies during one decade has decreased by 34%. The national prospective FINHYST study in 1996 showed abdominal hysterectomy (AH) as being most common: 58%. In Finland since 2002, vaginal hysterectomy (VH) has been most preferred, with laparoscopic hysterectomy (LH) surpassing AH in 2005. METHODS: FINHYST 2006 is a national prospective hysterectomy study in which all hospitals collaborated from 1 January to 31 December 2006. Questionnaires, completed by gynaecologists, covered their experience, patient characteristics and surgical data. RESULTS: The 5279 hysterectomies distributed by approaches were 44% VHs, 32% LHs and 24% AHs. Less than 2% were subtotal. The main indications for hysterectomy were myomas (33%), uterine prolapse (28%) and menorrhagia (21%). The main indication for VH was not related to uterine prolapse in 39%. Bilateral salpingo-ooforectomy was performed in 36% of AHs, 32% of LHs and 2% of VHs. Antibiotic prophylaxis was used in 97%, and thrombosis prophylaxis in 65%. Haemorrhage was least and operation time shortest with VH, and hospital stay and sick leave were shortest after LH. CONCLUSIONS: In Finland, less invasive approaches comprise 76% of hysterectomies. This trend has resulted nationally in shortening of hospital stay and of convalescence time.

Expression of hyaluronan synthases (HAS1-3) and hyaluronidases (HYAL1-2) in serous ovarian carcinomas: inverse correlation between HYAL1 and hyaluronan content.

BACKGROUND: Hyaluronan, a tumor promoting extracellular matrix polysaccharide, is elevated in malignant epithelial ovarian tumors, and associates with an unfavorable prognosis. To explore possible contributors to the accumulation of hyaluronan, we examined the expression of hyaluronan synthases (HAS1, HAS2 and HAS3) and hyaluronidases (HYAL1 and HYAL2), correlated with hyaluronidase enzyme activity hyaluronan content and HAS1-3 immunoreactivity. METHODS: Normal ovaries (n = 5) and 34 serous epithelial ovarian tumors, divided into 4 groups: malignant grades 1+2 (n = 10); malignant grade 3 (n = 10); borderline (n = 4) and benign epithelial tumors (n = 10), were analyzed for mRNA by real-time RT-PCR and compared to hyaluronidase activity, hyaluronan staining, and HAS1-3 immunoreactivity in tissue sections of the same specimens. RESULTS: The levels of HAS2 and HAS3 mRNA (HAS1 was low or absent), were not consistently increased in the carcinomas, and were not significantly correlated with HAS protein or hyaluronan accumulation in individual samples. Instead, the median of HYAL1 mRNA level was 69% lower in grade 3 serous ovarian cancers compared to normal ovaries (P = 0.01). The expression of HYAL1, but not HYAL2, significantly correlated with the enzymatic activity of tissue hyaluronidases (r = 0.5; P = 0.006). An inverse correlation was noted between HYAL1 mRNA and the intensity of hyaluronan staining of the corresponding tissue sections (r = -0.4; P = 0.025). CONCLUSION: The results indicate that in serous epithelial ovarian malignancies HAS expression is not consistently elevated but HYAL1 expression is significantly reduced and correlates with the accumulation of hyaluronan. (233 words).

HRT and Vit D in prevention of non-vertebral fractures in postmenopausal women; a 5 year randomized trial.

OBJECTIVES: We investigated the incidence of new non-vertebral fractures during HRT or low-dose vitamin (Vit) D3 supplementation in a 5-year prospective trial. METHODS: A total of 464 early postmenopausal women, (a subgroup of the Kuopio Osteoporosis Study, n = 13100) were randomized to four groups: (1) HRT, a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate; (2) Vit D (300 IU/day and 100 IU/day during the fifth year); (3) HRT + Vit D; and (4) placebo. Lumbar (L2-4) and femoral neck bone mineral densities (BMD) were determined by dual X-ray absorptiometry (DXA) at baseline, after 2.5 and 5 years of treatment. All new symptomatic non-vertebral, radiographically defined fractures were recorded. RESULTS: Altogether, 368 women (79%) completed the 5 year treatment. In all, 32 women had 39 non-vertebral fractures during a mean of 4.3 year follow-up (HRT 4, Vit D 10, HRT + Vit D 8 and placebo 17). The reduction in the incidence of new non-verterbral fractures was significant in women with HRT alone (P = 0.032) when adjusted by baseline BMD and previous fractures; observed also with the intention-to-treat principle (P = 0.048). When the HRT groups were pooled, HRT showed a significantly lower incidence of new non-vertebral fractures (P = 0.042) than women receiving placebo and also after adjusting as above (P = 0.016); both in valid-case and in the intention-to-treat analysis. In the Vit D group, the fracture incidence was non-significantly decreased (P = 0.229) in comparison with the placebo group. The estimated risk of new non-vertebral fractures among women treated with HRT alone was 0.29 (95% CI, 0.10-0.90) and with Vit D 0.47 (95% CI, 0.20-1.14) and with HRT + Vit D 0.44 (95% CI, 0.17-1.15), in comparison with the placebo group (adjusted by femoral BMD and previous fractures). CONCLUSIONS: This study is the first prospective trial confirming the beneficial effect of HRT on prevention of peripheral fractures in non-osteoporotic postmenopausal women. The effect of low-dose Vit D remains to be proved.

Hormonal contraceptive users' self-reported benefits, adverse reactions, and fears in 2001 and 2007.

BACKGROUND: Hormonal contraceptives (HCs) are the most common contraceptive method in western countries. The fears and problems experienced by users of HCs can have an impact on their quality of life, and lead to abortions and unwanted pregnancies. OBJECTIVE: To investigate whether experiences and perceptions of HC users in Finland have changed from 2001 to 2007. METHODS: Data were collected using questionnaire surveys of women using HCs in 2001 and 2007. In Finland, HCs are available with a physician's prescription, and are only supplied in community and university pharmacies. University pharmacies in 12 large cities across Finland were selected to distribute the questionnaires. The response rate was 53% (n = 264) in 2001 and 55% (n = 436) in 2007. The average age of the respondents was 26 years in both surveys. The surveys measured self-reported benefits and adverse reactions, preconceptions, fears, knowledge, and opinions. RESULTS: The number of HC users reporting fears increased from 2001 to 2007 (p = 0.002), whereas the number of HC users reporting adverse reactions decreased (p = 0.013). In both surveys, the most common fear was infertility after HC use (17% vs 26% for 2001 and 2007, respectively). In both surveys, the most common benefits were efficacy and regular menstrual cycle, and the most common adverse reactions were mood swings, lowered libido, and weight gain. CONCLUSIONS: Our study suggests that, although women using HCs were convinced about their benefits, and the number of users reporting adverse reactions had decreased from 2001 to 2007, the number of users reporting fears had increased. Healthcare professionals need to provide counseling in order to alleviate women's fears and to correct false perceptions of HCs.

Do Finnish women using hormone replacement therapy need more information about risks.

OBJECTIVE: In 1998, the Women's Health Initiative (WHI) in 2002 and the Million Women Study (MWS) in 2003 have shown a need for re-evaluation of the benefits and adverse reactions of hormone replacement therapy (HRT). Consequently the authorities in Europe and USA have issued new recommendations against the use of HRT. The aim of this study was to examine women's perceptions of HRT since the publication of the Women's Health Initiative study and the Million Women Study, and the kind of sources women use to obtain information about HRT. METHOD: The data was collected with questionnaire survey in the autumn 2003 among 315 women using HRT. RESULTS: One third of the respondents (35%) had experienced fears concerning HRT use, and more than half (52%) reported that the debate in the media had markedly influenced them; they have experienced fears or worries, considered discontinuation or discussed with the physician. Whereas the most common source of information concerning the benefits of HRT was the physician (74%), the most common source of information concerning the risks of HRT was the media (78%). CONCLUSION: This study shows that women using HRT should get more information about the risks from health care professionals. Physicians and pharmacists have an opportunity to alleviate fears and to help women to critically evaluate the information they get from the media. Such discussions are also important to women who have been using HRT for years.

Leucine7 to proline7 polymorphism in prepro-NPY gene and femoral neck bone mineral density in postmenopausal women.

Neuropeptide Y (NPY) is a versatile neurotransmitter that has recently been shown to regulate bone metabolism in animal and in vitro studies. We studied the influence of leucine7-to-proline7 (Leu7/Pro7) polymorphism of the NPY signal peptide gene on bone mineral density (BMD) before and after a 5-year hormone replacement therapy (HRT) in 316 early postmenopausal women participating in a randomized controlled trial nested in the population-based Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study. The participants were randomized into two treatment groups: the HRT group (n = 146) received a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate and calcium lactate, 500 mg/day (equal to 93 mg Ca2+) alone or in combination with vitamin D3, 100-300 IU/day. The non-HRT group (n = 170) received calcium lactate, 500 mg alone or in combination with vitamin D3, 100-300 IU/day. BMDs of the lumbar spine (L2-4) and proximal femur were measured by using dual X-ray absorptiometry (DXA). The frequency of Leu7/Pro7 polymorphism was 15.2%. At baseline, there were no significant differences in the lumbar or femoral neck BMD between the subjects who had Leu7Pro7 polymorphism and the normal subjects. After 5 years, the BMD of the femoral neck remained unaltered and that of the lumbar spine increased by 1.7% in the HRT group, whereas both BMDs were decreased by 4-5% in the non-HRT group. After 5 years, the femoral neck BMD was significantly lower in those with the wild-type NPY polymorphism than in those with Leu7/Pro7 polymorphism (P = 0.040) in the non-HRT group. In the HRT group, the changes in BMD were quite modest and not significantly modified by Leu7/Pro7 genotype. We conclude that the Leu7/Pro7 polymorphism in NPY signal gene may favorably affect femoral neck BMD in postmenopausal women.

Relation of aromatase gene polymorphism and hormone replacement therapy to serum estradiol levels, bone mineral density, and fracture risk in early postmenopausal women.

BACKGROUND: After the menopause, estrogen synthesis from androgens and androgen precursors by aromatase is the main source of circulating estrogens. AIM: To evaluate whether aromatase gene (CYP19)polymorphism affects circulating estradiol (E2) levels, bone mineral density (BMD), BMD change or fracture risk. METHODS: A 5-year randomized hormone replacement therapy (HRT) trial on 331 early postmenopausal women (mean baseline age 52.7 +/- 2.3 years). The participants consisted of two treatment groups: the HRT group (n = 151) received a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate with or without vitamin D3, 100-300 IU + 93 mg calcium as lactate/day, and the non-HRT group (n = 180) received 93 mg calcium alone or in combination with vitamin D3, 100-300 IU/day for 5 years. BMD was measured from lumbar spine and proximal femur (DXA) before and after the 5-year trial. All new symptomatic, radiographically defined fractures were recorded during the follow-up. The polymorphism (intron 4 TTTA repeat) of CYP19 was evaluated after PCR amplification of the polymorphic site. CYP19 polymorphism was divided into three repeat groups: short (length of 7 or 8 in both alleles; n = 135), long (length of 11 or higher in both alleles; n = 47), and medium (rest of the values; n = 149). RESULTS: Of the baseline characteristics, only physical activity was associated with CYP19 polymorphism (P = 0.04) and a borderline significance was observed with previous fractures (P = 0.05). In the HRT or non-HRT groups, the 5-year serum E2 change was not associated with CYP19 polymorphism (P = 0.87 and 0.74, respectively). Further, the polymorphism did not influence the calculated annual changes of lumbar or femoral neck BMD during the 5-year follow-up in the HRT (P = 0.60 and 0.17, respectively) or non-HRT (P = 0.92 and 0.80, respectively) groups. In all, 28 women sustained 33 fractures during the follow-up. The CYP19 polymorphism was not significantly associated with fracture risk (P = 0.89 and 0.23 respectively; Cox proportional hazards model) in the HRT or non-HRT groups. CONCLUSIONS: CYP19 polymorphism was not associated with circulating E2 levels, BMD values, or fracture risk in these early postmenopausal Finnish women. If such an association exists in women, it may become apparent in older age groups.

Relation of androgen receptor gene polymorphism to bone mineral density and fracture risk in early postmenopausal women during a 5-year randomized hormone replacement therapy trial.

In women, the influence of androgens on bone health is not clear. It has been suggested that the androgen receptor (AR) genotype is associated with bone mineral density and serum androgen levels in pre- and perimenopausal women, but the association between AR genotype, bone mineral density, and fracture risk has not been studied in postmenopausal women. Therefore, we studied whether AR polymorphism affects bone mineral density, bone mineral density change, or fracture risk in a 5-year randomized hormone replacement therapy (HRT) trial on 331 early postmenopausal women (mean baseline age, 52.7 +/- 2.3 years). The participants consisted of two treatment groups: the HRT group (n = 151) received a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate with or without vitamin D3, 100-300 IU + 93 mg calcium as lactate/day, and the non-HRT group (n = 180) received 93 mg calcium alone or in combination with vitamin D3, 100-300 IU/day for 5 years. Bone mineral density was measured from lumbar spine and proximal femur (DXA) before and after the 5-year trial. All new symptomatic, radiographically defined fractures were recorded during the follow-up. The length of CAG repeat in exon 1 of AR gene was evaluated after polymerase chain reaction (PCR) amplification. The subjects were divided into three repeat groups according to AR alleles. None of the baseline characteristics were associated with AR gene polymorphism and HRT treatment. The polymorphism did not influence the calculated annual changes of lumbar or femoral neck bone mineral density during the 5-year follow-up in the HRT (p = 0.926 and 0.146, respectively) or non-HRT (p = 0.818 and 0.917, respectively) groups. In all, 28 women sustained 33 fractures during the follow-up. Thus, the numbers of fractures were limited. The AR repeat length variation was not significantly associated with fracture risk in the HRT or non-HRT groups (p = 0.632 and 0.459, respectively; Cox proportional hazards model). In conclusion, AR gene polymorphism was not associated with baseline bone mineral density, 5-year bone mineral density change, or fracture risk in early postmenopausal Finnish women.