Premature ovarian insufficiency - the need for a genomic map.

Premature ovarian insufficiency (POI) is a life-long disorder of heterogeneous etiology, presenting as adolescent primary amenorrhea in its most severe form, with an overall incidence of 1%. Idiopathic POI accounts for up to 70% of women with POI; and genomic, genetic, epidemiological, familial and cohort studies demonstrate a genetic component to this condition. Currently, the only genetic tests routinely performed in non-syndromic POI are FMR1 premutation and cytogenetics, the latter specifically for X-chromosome abnormalities. However, a myriad of genetic aberrations has been identified and implicated, some of which act in a monogenic Mendelian fashion. The presence of multiple genetic aberrations and the complexity of POI genomics are hardly surprising since the embryological formation of the primordial oocyte pool, postnatal oogenesis and folliculogenesis are all highly complex pathways. With this review, the aim is to discuss the current genetic etiologies in the emerging field of POI genomics. Promising candidate genes include STAG3, SYCE1, FIGLA, NOBOX, FSHR, BMP15 and INHA. This area has the potential to progress rapidly in light of advances in genomic technologies. The development of a POI genomic map not only will assist in understanding the underlying molecular mechanisms affecting ovarian function but will also be essential in designing predictive and diagnostic gene panels as well as future novel therapeutic strategies.

Work-related post-traumatic stress symptoms in obstetricians and gynaecologists: findings from INDIGO, a mixed-methods study with a cross-sectional survey and in-depth interviews.

OBJECTIVES: To explore obstetricians' and gynaecologists' experiences of work-related traumatic events, to measure the prevalence and predictors of post-traumatic stress disorder (PTSD), any impacts on personal and professional lives, and any support needs. DESIGN: Mixed methods: cross-sectional survey and in-depth interviews. SAMPLE AND SETTING: Fellows, members and trainees of the Royal College of Obstetricians and Gynaecologists (RCOG). METHODS: A survey was sent to 6300 fellows, members and trainees of RCOG. 1095 people responded. Then 43 in-depth interviews with trauma-exposed participants were completed and analysed by template analysis. MAIN OUTCOME MEASURES: Exposure to traumatic work-related events and PTSD, personal and professional impacts, and whether there was any need for support. Interviews explored the impact of trauma, what helped or hindered psychological recovery, and any assistance wanted. RESULTS: Two-thirds reported exposure to traumatic work-related events. Of these, 18% of both consultants and trainees reported clinically significant PTSD symptoms. Staff of black or minority ethnicity were at increased risk of PTSD. Clinically significant PTSD symptoms were associated with lower job satisfaction, emotional exhaustion and depersonalisation. Organisational impacts included sick leave, and 'seriously considering leaving the profession'. 91% wanted a system of care. The culture in obstetrics and gynaecology was identified as a barrier to trauma support. A strategy to manage the impact of work-place trauma is proposed. CONCLUSIONS: Exposure to work-related trauma is a feature of the experience of obstetricians and gynaecologists. Some will suffer PTSD with high personal, professional and organisational impacts. A system of care is needed. TWEETABLE ABSTRACT: 18% of obstetrics and gynaecology doctors experience post-traumatic stress disorder after traumatic events at work.

Out of focus: tailoring the cascade of care to the needs of women living with HIV.

Around half of the global adult HIV-positive population are women, yet historically women have been under-represented in clinical studies of antiretroviral therapy (ART) and there has been minimal exploration of gender-specific factors related to the response to and appropriateness of treatment choices in women living with HIV (WLWH). There are several key issues pertaining to the cascade of HIV care that make it important to differentiate WLWH from men living with HIV. Factors that are gender specific may impact on the status of WLWH, affecting access to diagnosis and treatment, optimal clinical management, ART outcomes, retention in care, and the overall long-term wellbeing of WLWH. In this review, we discuss the results of recently reported women-only clinical trials and highlight the key unmet needs of WLWH as they pertain to the cascade of HIV care across World Health Organization European Region countries. As significant knowledge gaps remain, the review identifies key areas where further research is required, in order to support improved management of WLWH and guide informed clinical decision-making, including addressing psychosocial factors as part of comprehensive care.

Chronic urticaria due to autoreactivity to progesterone.

A 23-year-old, regularly menstruating woman presented with recurrent urticarial eruptions, which occurred premenstrually. A skin prick test was positive for progesterone, but the urticaria was unresponsive to standard treatments. The patient was treated with goserelin (Zoladex), which suppressed her menstrual cycle, leading to the resolution of her symptoms. Subsequent flares were controlled by further goserelin injections, and the urticaria is currently in remission. However, the risks of inducing menopause artificially are significant, and alternative long-term solutions may need to be considered in the event of a relapse.

Sexual quality of life in women who have undergone female genital mutilation: a case-control study.

OBJECTIVE: To investigate the sexual quality of life of women who have undergone female genital mutilation (FGM) and compare them with a similar group who has not undergone FGM. DESIGN: Case-control study. SETTING: A large central London teaching hospital. POPULATION: A total of 73 women who had undergone FGM and 37 control women, who had not undergone FGM but were from a similar cultural background where FGM is practiced. METHODS: The women completed a questionnaire containing the Sexual Quality of Life-Female (SQOL-F) questionnaire. MAIN OUTCOME MEASURES: SQOL-F score. RESULTS: Women who have undergone FGM of any type have a significantly lower (P < 0.001) overall SQOL-F score than control women (mean = 62.44, SD = 27.93 versus mean = 88.84, SD = 13.73). Women who were sexually active and had undergone FGM type III differed the most from sexually active controls (P < 0.05) in their SQOL-F score. Women who were sexually inactive but who had undergone FGM reported significantly lower overall SQOL-F scores (P = 0.015) than sexually inactive controls, but were not differentiated by type of FGM. CONCLUSION: FGM significantly reduces women's sexual quality of life, based on the results of the SQOL-F questionnaire.

A service evaluation of women attending the menopause/premature ovarian failure clinic of a tertiary referral centre.

This service evaluation aimed to characterise the referrals to the premature ovarian failure clinic, including the type of referral and patient needs, in order to plan for future service provision. The majority of women seen in the clinic experienced idiopathic premature ovarian failure, were aged 30-39 and were nulliparous at the time of diagnosis. Our service requires to be tailored to their needs. For many women, this includes a fertility consultation in the clinic and this part of the service is well used. Our data support the long-term follow-up of women both on treatment and those who initially decline treatment. Most women who initially decline treatment accept it after a few clinic visits. This may be due to consistent advice on the benefits of oestrogen treatment or due to yearly bone scans showing a change in bone density. There was a high non-attendance rate in this group: 21% of appointments were not attended.

Menopause care in women living with HIV in the UK - A review.

Advances in HIV care over the last 30 years have transformed a virtually fatal condition into a chronic, manageable one. Antiretroviral therapy (ART) has dramatically changed the outlook for people living with HIV so that most individuals with well controlled disease have a normal life expectancy. As result of this increase in life expectancy, one-third of women living with HIV are of menopausal age. Adding to the shift in age distribution, rates of new HIV diagnosis are increasing in the over 50-year age group, likely the result of a combination of low condom use and perception of transmission risk and in women, an increased risk of HIV acquisition due to the mucosal disruption that accompanies vaginal atrophy. Many women living with HIV are unprepared for menopause, have a high prevalence of somatic, urogenital and psychological symptomatology and low rates of menopausal hormone therapy (MHT) use. Many women experience enormous frustration shuttling between their general practitioner and HIV care provider trying to have their needs met, as few HIV physicians have training in menopause medicine and primary care physicians are wary of managing women living with HIV, in part, because of fears about potential drug-drug interactions (DDIs) between MHT and ART. Several data gaps exist with regard to the relationship between HIV and the menopause, including whether the risk of HIV transmission is increased in virally-suppressed women with vaginal atrophy, whether or not menopause amplifies the effects of HIV on cardiovascular, psychological and bone health, as well as the safety and efficacy of MHT in women living with HIV. Menopausal women living with HIV deserve high quality individualised menopause care that is tailored to their needs. More research is needed in the field of HIV and menopause, primarily on cardiovascular disease and bone health outcomes as well as symptom control, and strategies to reduce HIV acquisition, encourage testing, and maintain older women in care in order to inform optimal clinical management.

The effect of weight and weight change on the long-term precision of spine and hip DXA measurements.

SUMMARY: We examined the effect of weight and weight change on the long-term precision of spine and hip bone mineral density (BMD) in a group of 64 postmenopausal women studied over a 10-year period. Long-term precision errors were 50% larger than short-term errors. Over the range 50-90-kg weight was associated with a statistically significantly larger precision error when precision was expressed in BMD units, but not when expressed as the coefficient of variation (CV). Weight changes up to 5 kg had little effect on precision. INTRODUCTION: Reliable knowledge of the precision of bone mineral density (BMD) measurements is important for the interpretation of follow-up dual-energy X-ray absorptiometry (DXA) scans. In this study, we examined the effect of body weight and change in weight on the long-term precision of spine and hip BMD. METHODS: The study population was a group of 64 postmenopausal women enrolled in a 16-year trial of tibolone. We analyzed the spine, femoral neck, and total hip BMD data acquired over a 10-year period on a Hologic QDR4500A densitometer using linear regression to examine the trend of BMD with time for each subject. Precision was expressed in BMD units (g cm(-2)) (standard error of the estimate, SEE) and also as the coefficient of variation (CV). RESULTS: The long-term precision errors were in BMD (CV) units: 0.018 g cm(-2) (1.9%) for spine, 0.017 g cm(-2) (2.3%) for femoral neck, and 0.016 g cm(-2) (1.7%) for total hip BMD. An inverse relationship between CV and BMD was found for the spine (P = 0.003) and total hip (P = 0.043) sites, but none between SEE and BMD. For spine BMD, there were statistically significant correlations between SEE and weight (P = 0.025) and body thickness (P = 0.027). For femoral neck BMD, there were correlations between SEE and weight (P = 0.030), body mass index (BMI) (P = 0.023) and thickness (P = 0.021), but no correlations for total hip BMD or when precision was expressed as the CV. When study subjects were grouped in quartiles according to weight, the spine BMD SEE increased from 0.014 g cm(-2) for women in the lowest quartile (46-62 kg) to 0.018 g cm(-2) for women in the highest quartile (80-105 kg) (P = 0.008). There was a trend for SEE to be greater in individuals with larger weight changes, although these tended to be the heavier subjects. CONCLUSIONS: From the study, we were able to come up with the following conclusions: (1) long-term precision errors were 50% larger than short-term errors, (2) over the range 50 to 90 kg (BMI: 20-35 kg m(-2)), body weight had a small but statistically significant effect on precision expressed in BMD units, but not when expressed as the CV, and (3) weight changes up to 5 kg had little effect on precision. More studies of individuals >100 kg are required to fully investigate the dependence of DXA scan precision on weight.

The management of menopausal symptoms in women following treatment for cancer at a specialist menopause service.

OBJECTIVE: The aim of this study was to identify prescribing patterns at a specialist menopause service in a central London teaching hospital for women following treatment for a malignancy. STUDY DESIGN: This was a prospective cohort study with data collected over a seven-month period from December 2019 to June 2020. All women reviewed at the specialist menopause services following treatment of a malignancy, BRCA carriers and Lynch syndrome were included in the study, with management options divided into three categories: hormonal, non-hormonal and no treatment. MAIN OUTCOME MEASURES: The primary outcome of this study was to identify prescribing patterns for all women reviewed following a diagnosis of a malignancy, as well as those with genetic mutations necessitating risk-reducing prophylactic bilateral salpingo-oopherectomy (BSO). RESULTS: Altogether 71 women were included in this study, with the majority of women post management of a non-gynaecological malignancy (51/71, 72%), of which breast cancer was the most common (37/71, 52%). While non-hormonal treatment was the most popular among those treated for breast cancer, for all other malignancies, hormonal treatment was more widespread. Fourteen women also had genetic mutations, with all of these women commencing hormonal treatment post risk reducing surgery. CONCLUSION: With the exception of those with a history of hormone-sensitive breast cancer, the use of hormonal treatment for menopausal symptoms remained widespread. While this was a relatively small study, the need for long-term follow-up across specialist menopause services, to assess the risk of recurrence is vital.

The testosterone prescribing practice of BMS menopause specialists.

The NICE Guidelines published in 2015 state that testosterone supplementation can be considered for menopausal women with low sexual desire if hormone replacement therapy alone is not effective. There is however, no detail on what to prescribe, how much to prescribe or whether monitoring is required. At the time of conception of this project, there was no national guideline or official advice from the British Menopause Society. We decided to ask menopause experts from around the UK to see if a consensus could be reached about good prescribing practice. The method and results as discussed below may be helpful in future recommendations and guidance.

Evaluation of a tertiary and district general hospital menopause service.

OBJECTIVE: Requests for management of menopausal symptoms and hormone replacement are increasing in the UK. Referrals to specialist clinics have to be balanced with increasing recommendations within the NHS to improve efficiency and patient care. STUDY DESIGN: Retrospective evaluation of clinic records over two months at a district general (Poole Hospital) and tertiary (Guy's Hospital) menopause service. Data on referral origin, reason for referral, interval from referral to review and outcome were collected and compared between trusts. MAIN OUTCOME MEASURES: To evaluate and compare referrals and outcomes in a tertiary and district general menopause service and provide recommendations for improving efficiency. RESULTS: Most referrals are from primary care but up to 25% are from other specialties. Half of the appointments are new referrals and 95% of women attend. Of the new referrals, 50% have multiple medical comorbidities, 25% a personal or family history of cancer and 25% treatment resistance; 30% have premature ovarian insufficiency. At Guy's Hospital, 30% are reviewed more than 18 weeks after referral, at Poole Hospital this is 6%. Treatment resistance is reported in half of the women reviewed at follow-up. CONCLUSIONS: Menopause services review a complex patient population and the majority of referred women have more than one co-morbidity; they require time, specialist knowledge of current treatment options and a multidisciplinary approach. The main barrier to service efficiency is capacity, particularly in population dense areas; cognitive behavioural therapy and non-hormonal methods appear under-utilised in primary care, as do alternative methods of follow-up within the clinics such as telephone and patient-initiated appointments.

What can be done about hot flushes after treatment for breast cancer?

Breast cancer survivors frequently experience severe hot flushes as a result of their treatment. This can adversely affect their quality of life, compliance with treatment and overall survival. To relieve vasomotor symptoms, a variety of drugs have been used including clonidine, gabapentin, selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors. Stellate ganglion block (SGB) has recently emerged as a new technique against hot flushes and preliminary studies report encouraging efficacy with minimal complications. Other approaches include various alternative treatments and, in a few cases, hormone replacement therapy (HRT). All randomized, controlled studies of drugs, hormone treatments and alternative therapies for vasomotor symptoms have been reviewed and efficacy and safety noted. Side-effects of current medical treatments frequently outweigh the benefits--leading many patients to discontinue the medications. Statistically significant differences between placebo and test agent may not translate into a meaningful subjective benefit. Desvenlafaxine looks promising as does SGB, despite its invasive nature. The favorable safety profile of SGB is confirmed through the long experience of SGB performed for other medical purposes. The majority of non-HRT treatments for hot flushes are little better than placebo but early results from randomized trials of desvenlafaxine and pilot studies of SGB suggest that it is worthwhile to test their efficacy specifically in breast cancer survivors.

Testosterone treatment of HSDD in naturally menopausal women: the ADORE study.

OBJECTIVE: To evaluate the efficacy and safety of a transdermal testosterone patch (TTP, 300 microg/day) in naturally menopausal women with hypoactive sexual desire disorder (HSDD). METHODS: A total of 272 naturally menopausal women, predominantly not using hormone therapy, were randomized in this 6-month, placebo-controlled, double-blind, multicenter study to receive twice weekly either TTP or an identical placebo. Efficacy endpoints measured were the 4-week frequency of satisfying sexual episodes (SSE) using the Sexual Activity Log, the sexual desire domain of the Profile of Female Sexual Function and distress by the Personal Distress Scale. Safety was assessed by adverse events, laboratory parameters and hormone levels. RESULTS: The TTP group demonstrated significant improvements in SSE (p = 0.0089) as well as in sexual desire (p = 0.0007) and reduced personal distress (p = 0.0024) versus placebo at 6 months (intent-to-treat analysis, n = 247). The results were significant for all three endpoints in the subgroup (n = 199) not using hormone therapy. Similar numbers of women treated with placebo and TTP discontinued (n = 39, 27.5% vs. n = 26, 20%), reported adverse events (including application site reactions) (n = 101, 71.1% vs. n = 81, 62.3%) and withdrew due to adverse events (n = 20, 14.1% vs. n = 9, 6.9%). No clinically relevant changes were noted in laboratory parameters. Serum free and total testosterone levels increased from baseline in the TTP group (geometric means 5.65 pg/ml and 67.8 ng/dl, respectively, at week 24) within the physiological range; no changes were seen in estradiol and sex hormone binding globulin levels. CONCLUSIONS: TTP was effective in treating HSDD and improving sexual function in this study of naturally menopausal women with and without concurrent hormone therapy.

The interactive effect of the cholinergic system and acute ovarian suppression on the brain: an fMRI study.

Recent evidence suggests that loss of ovarian function following ovariectomy is a risk factor for Alzheimer's disease (AD); however, the biological basis of this risk remains poorly understood. We carried out an fMRI study into the interaction between loss of ovarian function (after Gonadotropin Hormone Releasing Hormone agonist (GnRHa) treatment) and scopolamine (a cholinergic antagonist used to model the memory decline associated with aging and AD). Behaviorally, cholinergic depletion produced a deficit in verbal recognition performance in both GnRHa-treated women and wait list controls, but only GnRHa-treated women made more false positive errors with cholinergic depletion. Similarly, cholinergic depletion produced a decrease in activation in the left inferior frontal gyrus (LIFG; Brodmann area 45)--a brain region implicated in retrieving word meaning--in both groups, and activation in this area was further reduced following GnRHa treatment. These findings suggest biological mechanisms through which ovarian hormone suppression may interact with the cholinergic system and the LIFG. Furthermore, this interaction may provide a useful model to help explain reports of increased risk for cognitive decline and AD in women following ovariectomy.

A comparison of hormone therapies on the urinary excretion of prostacyclin and thromboxane A2.

OBJECTIVE: To evaluate the effect of estradiol, estradiol and norethisterone acetate (NETA), raloxifene and tibolone on the prostacyclin (PGI(2))/thromboxane A2 (TxA(2)) ratio in postmenopausal women after 8 weeks of treatment. DESIGN: This was a randomized, double-blind, cross-over study. Each patient took 8-week courses of estradiol 2 mg, estradiol 2 mg + NETA 1 mg, tibolone 2.5 mg, and raloxifene 60 mg; there was an 8-week placebo wash-out between each different intervention. All volunteers took all four treatment options and were randomized to one of three possible sequences. Urine was collected and frozen at each visit. Urinary metabolites of PGI(2) and TxA(2) were then assessed at the end of the study. RESULTS: The ratio of PGI(2)/TxA(2) was significantly increased for raloxifene. No other treatments showed statistically significant changes. CONCLUSIONS: The relationship between cardiovascular risk and hormone replacement therapy remains poorly understood. Raloxifene may have additional cardioprotective effects that the other treatments did not demonstrate, and none of the treatments statistically worsened the PGI(2)/TxA(2) ratio. This ratio may be under-utilized as a marker of net effect on cardiovascular health, but more research is needed to link it to health outcomes.

Epinephrine-induced increases in [Ca2+](in) and KCl-coupled fluid absorption in bovine RPE.

PURPOSE: To define the ionic basis for the apical epinephrine-induced increase of fluid absorption (J(V)) across isolated bovine RPE-choroid. METHODS: Epinephrine-induced changes in RPE [Ca2+](in) levels were monitored with the ratioing dye fura-2. Transepithelial potential, resistance, and unidirectional fluxes of (36)Cl, (86)Rb (K substitute), and (22)Na were simultaneously determined in paired tissues from the same eye mounted in modified Ussing flux chambers. Radioisotopes (5-7 microCi) were added to the apical bath of one tissue and the basal bath of the other, and the appearance of label in the opposite bath was measured. RESULTS: Apical epinephrine (100 nM) transiently increased [Ca2+](in) by 153 +/- 78 nM. This increase was inhibited by the alpha(1)-adrenoreceptor antagonist prazosin (1 microM) and blocked by CPA(5 microM), an inhibitor of endoplasmic reticulum Ca2+-adenosine triphosphatases (ATPases). Apical epinephrine (100 nM) more than doubled the net Cl absorption rate, increased net K ((86)Rb) absorption by fivefold, and tripled net fluid absorption (J(V)), as predicted by isotonic coupling between ion and fluid transport. The epinephrine-induced increases in ion and fluid transport were completely inhibited by apical bumetanide (100 microM). CONCLUSIONS: Epinephrine increased fluid absorption across bovine RPE by activating apical membrane alpha(1)-adrenergic receptors, increasing [Ca2+](in), and stimulating bumetanide-sensitive Na,K,2Cl uptake at the apical membrane and KCl efflux at the basolateral membrane.

Effect of long-term estrogen therapy on dopaminergic responsivity in post-menopausal women--a preliminary study.

Females have a higher prevalence than men of neuropsychiatric disorders in which dopaminergic abnormalities play a prominent role, e.g. very late-onset schizophrenia and Parkinson's disease (PD). The biological basis of these sex differences is unknown but may include modulation of the dopaminergic system by sex hormones, as there is preliminary evidence that estrogen modulates treatment response in these disorders. Furthermore, sex differences in dopamine-mediated cognitive decline suggest estrogen may also play a role in healthy aging. However, the effects of estrogen on the dopaminergic system are poorly understood, and nobody has examined the effect of long-term estrogen therapy (ET) on this system. We compared dopaminergic responsivity (growth hormone (GH) response to apomorphine) in post-menopausal women on ET to women who were ET-naïve. GH response to subcutaneous apomorphine (0.005 mg/kg) was measured in two groups of healthy post-menopausal women aged between 55 and 70 years: those taking ET (n = 13) and those who had never taken ET (n = 13). Neither group was taking any other medication. GH was measured at 15 min intervals from -30 min before administration of apomorphine to 90 min post-administration. GH response was measured in two ways: area under the curve (AUC) and maximum response over baseline (GH). There were no between-group differences in demographic or baseline variables. The ET treated women had a significantly greater (p = 0.03) AUC than ET naïve women (mean +/- S.D.; 5.3 +/- 4.7 vs. 2.6 +/- 2.3). However, (GH) did not differ significantly between groups (6.1 mU/l +/- 6.2 vs. 2.7 mU/l +/- S.D. = 4.1). Also, analysis of GH response over time revealed a significant main effect of time (p < 0.0005), and a group by time interaction (p = 0.004) , but no significant main effect of group. Our results suggest that ET may enhance dopaminergic responsivity in post-menopausal women. Estrogen deficiency following menopause may partly explain age and gender differences in late-onset neuropsychiatric disorders.

Elevated serum sialic acid in pregnancy.

OBJECTIVE: Serum sialic acid has recently gained interest as a possible cardiovascular risk factor as well as a potential tumour marker. The effect of pregnancy on serum sialic acid is unclear particularly in the post-partum period. DESIGN: Longitudinal cohort. SETTING: Teaching hospital antenatal clinic. POPULATION: 29 pregnant women, 27 age matched non-pregnant women. METHODS: Specific enzymatic assay for sialic acid. The first serum sample was taken between 37 and 42 weeks of gestation; in 22 women this was followed by a second serum sample at 12 weeks postpartum. Serum sialic acid concentration was also measured in the 27 controls. RESULTS: Mean (SD) serum sialic acid concentration was higher during pregnancy than post-partum: 91.1 (11.1) v 77.5 (11.1) mg/dl (p < 0.001); or in the control group: 66.0 (9.7) mg/dl (p < 0.001). CONCLUSIONS: Serum sialic acid is elevated during pregnancy and postpartum.

Multicenter evaluation of the Elecsys CA 125 II assay.

The technical performance and clinical usefulness of the newly developed Elecsys CA 125 II assay (Boehringer Mannheim) was evaluated in a multicenter study. Imprecision studies were carried out using control sera and human pool sera with CA 125 concentrations from 11 to 1026 U/ml. Within-run CVs between 0.7 to 4.8% (median 1.7%) and between-day CVs between 2.4 to 10.9% (median 5.7%) were found. Method comparison studies with Enzymun-Test CA 125 II carried out in four laboratories yielded slopes between 0.94 to 1.07 and intercepts < 3 U/ml. A good comparability of the Elecsys CA 125 II assay was also found with one MEIA and the Centocor" IRMA. For a second MEIA and a second IRMA the slopes were 1.23 and 1.42, and the corresponding correlation coefficients were 0.987 and 0.977, respectively. The Elecys CA 125 II concentrations are clearly related to the tumor stage of ovarian carcinoma patients. The maximum of diagnostic efficiency of ovarian carcinoma patients compared with patients of benign gynecological diseases is reached at 150 U/ml with a specificity of 93% and a sensitivity of 69%. Follow-up studies of ovarian carcinoma patients reflect the status of the disease and the effect of various therapeutic applications. The technical and clinical evaluation of the Elecsys CA 125 II assay show a superior analytical performance with a broad measuring range up to 5000 U/ml and a short measuring time of 18 minutes.

A study of the effect of tibolone on the vagina in postmenopausal women.

Tibolone is a synthetic compound with weak oestrogenic, progestagenic and androgenic properties. It does not appear to stimulate the endometrium, and therefore has appeal to the postmenopausal woman as a 'bleedfree' form of hormone replacement therapy (HRT). In the present study the vaginal cytological findings and symptoms were evaluated in 100 recently postmenopausal women, 50 of whom were started on tibolone 2.5 mg daily and 50 of whom received no medication. After 2 years in the tibolone group, cytological assessment showed a significant increase in the karyopyknotic index (P < 0.001) and maturation value (P < 0.01) whereas there was no change in the control group. Significant symptomatic improvement occurred in vaginal dryness (P < 0.001), dyspareunia (P < 0.001), sexual enjoyment (P < 0.001) and libido (P < 0.05). It is therefore concluded that tibolone has a significant oestrogenic effect on the vagina as demonstrated by vaginal cytology. In addition, improvement in the symptoms of vaginal dryness, dyspareunia, sexual enjoyment and libido occurs.