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.

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.

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.

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.

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.

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.

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.

The interactive effect of acute ovarian suppression and the cholinergic system on visuospatial working memory in young women.

Women have an increased risk of developing Alzheimer's Dementia (AD) compared to men. It has been postulated that this risk may be modulated by a reduction in the neuroprotective effects of estrogen on the brain in the early postmenopausal period. This view is supported by, for example, findings that ovariectomy in younger women (i.e. prior to menopause) significantly increases the risk for the development of memory problems and AD in later life. However, the biological basis underlying these cognitive changes is still poorly understood. Our aim in the current study was to understand the interactive effects of acute, pharmacological-induced menopause (after Gonadotropin Hormone Releasing Hormone agonist (GnRHa) treatment) and scopolamine (a cholinergic antagonist used to model the memory decline associated with aging and AD) on brain functioning. To this end we used fMRI to study encoding during a Delayed Match to Sample (DMTS) (visual working memory) task. We report a relative attenuation in BOLD response brought about by scopolamine in regions that included bilateral prefrontal cortex and the left parahippocampal gyrus. Further, this was greater in women post-GnRHa than in women whose ovaries were functional. Our results also indicate that following pharmacological-induced menopause, cholinergic depletion produces a more significant behavioural deficit in overall memory performance, as manifest by increased response time. These findings suggest that acute loss of ovarian hormones exacerbate the effects of cholinergic depletion on a memory-related, behavioural measure, which is dependent on fronto-temporal brain regions. Overall, our findings point to a neural network by which acute loss of ovarian function may interact to negatively impact encoding.

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.

Attitudes and awareness of female genital mutilation: a questionnaire-based study in a Kenyan hospital.

There are considerable efforts in Kenya to increase awareness of the issues and health risks associated with female genital mutilation (FGM) through educational programmes. The Kenyan government formally outlawed FGM in 2001. This questionnaire-based study aimed to explore attitudes and awareness of FGM in Kenya with particular reference to the law, health complications and educational programmes. A significant decline in the prevalence of FGM was demonstrated and awareness of health complications of FGM shown to be the main factor causing this trend. The need for further efforts to eradicate the practice and the importance of religion and culture in shaping social attitudes was evident. The outlawing of FGM was considered a positive advance but may have the detrimental effect of deterring women from seeking medical assistance for complications relating to FGM.

Use of chaperones by obstetricians and gynaecologists: a cross-sectional survey.

The Royal College of Obstetrics and Gynaecologists (RCOG) recommends that a chaperone should be offered to every patient for an intimate examination. The use of chaperones has risen in primary care, but little is known about the practice of obstetricians and gynaecologists. Our aim was to determine the current attitudes and practices of Fellows and Members of the RCOG regarding chaperones during intimate examinations, both in public and private practice. A total of 800 Fellows and Members were asked to complete a 45-item questionnaire on their use of chaperones and how important a range of issues were in deciding whether or not to offer and provide a chaperone. A total of 449 questionnaires were returned. In summary, 23% of respondents never or occasionally offered a chaperone; 24% of NHS units have no agreed NHS policy and a further 16% did not know if a policy existed. In NHS practice, 77% used a chaperone with only 62% of women using a chaperone. Of those who did private practice, 34% never or occasionally offered a chaperone with 31% actually using a chaperone. In conclusion, obstetricians and gynaecologists use chaperones more than general practitioners but there is significant room for improvement. Chaperones are used more in NHS than private practice.

The influence of premenopausal hormones on severity of climacteric symptoms and use of HRT.

OBJECTIVES: There is wide variation in the severity of climacteric symptoms and we hypothesized that this could be a reflection of premenopausal hormone levels. METHODS: As part of a long-term cohort study of endocrine risk factors for breast cancer, blood had been collected between 1986 and 1990 from 1882 premenopausal women aged >or=35 years. Questionnaires on menopausal symptom severity were sent to 1,843 surviving women in 2001, of whom 1,434 replied. Estradiol, progesterone and testosterone levels were measured by radioimmunoassay in 680 women who reported a natural menopause and completed the symptom severity section in full. RESULTS: Symptom severity fell with rising premenopausal estradiol levels and women with higher premenopausal testosterone levels had more severe vasomotor symptoms. Over 70% of women with above-median severity of symptoms had used hormone replacement therapy (HRT). Those with higher testosterone levels were less likely to take HRT. CONCLUSIONS: Premenopausal hormone levels may predict risk of severe menopausal symptoms, which in turn influences use of HRT. Paradoxically, a high testosterone level was associated with more vasomotor symptoms but reduced use of HRT. Those at greatest risk of climacteric symptoms may be at lower risk of breast cancer because of premenopausal reduced estrogen exposure.