A novel estetrol-containing combined oral contraceptive: European expert panel review.

PURPOSE: Despite considerable advances in recently developed combined oral contraceptives (COCs), resulting in lower rates of adverse events while maintaining contraceptive efficacy, there is interest in further innovation. MATERIALS AND METHODS: Estetrol (E4), a native oestrogen, and progestin drospirenone (DRSP) were combined in a new COC. A European expert panel reviewed the pharmacology, efficacy, and safety and tolerability of this combination. Their findings are presented as a narrative review. RESULTS: E4 15 mg/DRSP 3 mg in a 24/4 regimen provided effective contraception with good cycle control, characterised by a predictable regular bleeding pattern and minimal unscheduled bleeding, together with a good safety profile. The combination was associated with high user satisfaction, well-being, and minimal changes in body weight. The effects on endocrine and metabolic parameters were limited, and the combination was found to have a limited impact on liver function and lipid and carbohydrate metabolism. Moreover, its effect on several haemostatic parameters was lower than that of comparators containing ethinyl oestradiol (EE) 20 µg/DRSP 3 mg and EE 30 µg/levonorgestrel 150 µg. CONCLUSION: E4 15 mg/DRSP 3 mg provides safe and effective contraception, with high user satisfaction and predictable bleeding. Further research will evaluate the long-term safety of the COC.

A Review of Clinical Guidelines on the Management of Iron Deficiency and Iron-Deficiency Anemia in Women with Heavy Menstrual Bleeding.

INTRODUCTION: Up to one-third of women of reproductive age experience heavy menstrual bleeding (HMB). HMB can give rise to iron deficiency (ID) and, in severe cases, iron-deficiency anemia (IDA). AIM: To review current guidelines for the management of HMB, with regards to screening for anemia, measuring iron levels, and treating ID/IDA with iron replacement therapy and non-iron-based treatments. METHODS: The literature was searched for English-language guidelines relating to HMB published between 2010 and 2020, using the PubMed database, web searching, and retrieval of clinical guidelines from professional societies. RESULTS: Overall, 55 guidelines mostly originating from North America and Europe were identified and screened. Twenty-two were included in this review, with the majority (16/22) focusing on guidance to screen women with HMB for anemia. The guidance varied with respect to identifying symptoms, the criteria for testing, and diagnostic hemoglobin levels for ID/IDA. There was inconsistency concerning screening for ID, with 11/22 guidelines providing no recommendations for measurement of iron levels and four contrasting guidelines explicitly advising against initial assessment of iron levels. In terms of treatment, 8/22 guidelines provided guidance on iron therapy, with oral iron administration generally recommended as first-line treatment for ID and/or IDA. Four guidelines recommended intravenous iron administration for severe anemia, in non-responders, or before surgery. Three guidelines provided hemoglobin thresholds for choosing between oral or intravenous iron treatment. Four guidelines discussed the use of transfusion for severe IDA. CONCLUSION: Many of the guidelines for managing HMB recognize the importance of treating anemia, but there is a lack of consensus in relation to screening for ID and use of iron therapy. Consequently, ID/IDA associated with HMB is likely to be underdiagnosed and undertreated. A consensus guidance, covering all aspects of screening and management of ID/IDA in women with HMB, is needed to optimize health outcomes in these patients.

Women who bleed heavily during menstruation are at risk of iron deficiency and anemia. This can have a negative effect on the well-being of women and can cause serious complications after surgery. Iron is an important part of the hemoglobin in red blood cells that carries oxygen around the body. Bleeding causes iron to be lost from the body. If there is heavy blood loss, iron stores in the body can become low, leading to iron deficiency. If the iron deficiency is severe enough to impair red blood cell production, iron-deficiency anemia can develop. We reviewed the current guidelines for the care of women with heavy menstrual bleeding, focusing on the detection and treatment of iron deficiency and anemia. Most guidelines include routine testing for anemia. Fewer guidelines consider measuring iron levels. Not all the guidelines include advice on the best way to treat iron deficiency and anemia. For those that do, the recommendations vary and sometimes offer conflicting advice. There is little agreement on when to give iron therapy, and whether this should be given by mouth or by infusion. A lack of clear guidance on detecting and treating iron deficiency and anemia caused by heavy menstrual bleeding puts women at risk of being undiagnosed and untreated. To address these concerns, the authors recommend the development of consensus guidelines. These should contain comprehensive recommendations on all aspects of the diagnosis and management of iron deficiency and anemia in women with heavy menstrual bleeding.

Pooled analysis of two randomized, open-label studies comparing the effects of nomegestrol acetate/17ß-estradiol and drospirenone/ethinyl estradiol on bleeding patterns in healthy women.

OBJECTIVES: To obtain more precise and detailed information regarding the bleeding patterns of nomegestrol acetate (NOMAC)/17ß-estradiol (E2) and drospirenone/ethinyl estradiol (DRSP/EE) and to identify whether baseline demographic characteristics were associated with unscheduled bleeding, absent scheduled bleeding, or amenorrhea. STUDY DESIGN: This analysis pooled results from two pivotal open-label, randomized trials that compared bleeding patterns of NOMAC/E2 and DRSP/EE. In the two studies 4317 women aged 18-50 years from 24 countries across the Americas, Europe, and Asia underwent treatment. RESULTS: 2835 women taking NOMAC/E2 (2.5 mg/1.5 mg) in a 24/4-day regimen and 938 women taking DRSP/EE (3 mg/30 µg) in a 21/7-day regimen had at least 1 evaluable cycle for vaginal bleeding analyses. The frequency of absent scheduled bleeding was higher (p<.0001) for women using NOMAC/E2 than DRSP/EE across all 11 cycles (cycles 2-12), ranging between 17.6% and 31.6% and between 3.4% and 5.8%, respectively. For women who had absent scheduled bleeding in cycles 2, 3, or 4 the incidence of absent scheduled bleeding in subsequent cycles was high and ranged between approximately 50%-60% for NOMAC/E2 and approximately 40%-50% for DRSP/EE. Amenorrhea increased over time with both regimens, being higher with NOMAC/E2. Both absent scheduled bleeding and amenorrhea with NOMAC/E2 were more common in older women, overweight women, switchers, and smokers; unscheduled bleeding was more common in starters, but had no association with age, body mass index, and smoking. CONCLUSIONS: NOMAC/E2 is associated with a higher prevalence of absent scheduled bleeding compared with DRSP/EE. Absent scheduled bleeding and amenorrhea were associated with age, body weight, switching and smoking. Unscheduled bleeding was more common in starters. IMPLICATIONS: Information about the factors associated with bleeding patterns may help clinicians provide guidance to women considering use of the NOMAC/E2 oral contraceptive.

Iron deficiency and iron deficiency anaemia in women.

Iron deficiency (ID) is the most common micronutrient deficiency worldwide with >20% of women experiencing it during their reproductive lives. Hepcidin, a peptide hormone mostly produced by the liver, controls the absorption and regulation of iron. Understanding iron metabolism is pivotal in the successful management of ID and iron deficiency anaemia (IDA) using oral preparations, parenteral iron or blood transfusion. Oral preparations vary in their iron content and can result in gastrointestinal side effects. Parenteral iron is indicated when there are compliance/tolerance issues with oral iron, comorbidities which may affect absorption or ongoing iron losses that exceed absorptive capacity. It may also be the preferred option when rapid iron repletion is required to prevent physiological decompensation or given preoperatively for non-deferrable surgery. As gynaecologists, we focus on managing women's heavy menstrual bleeding (HMB) and assume that primary care clinicians are treating the associated ID/IDA. We now need to take the lead in diagnosing, managing and initiating treatment for ID/IDA and treating HMB simultaneously. This dual management will significantly improve their quality of life. In this chapter we will summarise the importance of iron in cellular functioning, describe how to diagnose ID/IDA and help clinicians choose between the available treatment options.

A Survey of Bariatric Surgical and Reproductive Health Professionals' Knowledge and Provision of Contraception to Reproductive-Aged Bariatric Surgical Patients.

BACKGROUND: Over 80 % of bariatric surgical patients are women with obesity in their reproductive years. Obesity adversely affects fertility; the rapid weight loss following bariatric surgery can increase fecundity. Current guidelines recommend avoiding pregnancy for up to 24 months following surgery, but little is known about current contraceptive care of women who undergo bariatric surgery. Two surveys were undertaken with bariatric surgical and contraceptive practitioners in England to establish current contraceptive practices in both groups. METHODS: Two anonymous on-line surveys were sent to all 382 members of the British Obesity and Metabolic Surgery Society (BOMSS) and an estimated 300 contraceptive practitioners in the North East of England. RESULTS: The BOMSS survey elicited a response rate of 17 % (n = 65), mainly from bariatric surgeons (n = 24 (36 %)). Most respondents (97 %) acknowledged the need to educate patients, but contraceptive information was only provided by 7 % (n = 4) of respondents in bariatric surgical clinics. Less than half of respondents were confident discussing contraception, and the majority requested further training, guidance and communication with contraceptive practitioners. The majority of respondents to the contraceptive practitioner survey were general practitioners (28 %, n = 20). Three quarters of respondents reported little knowledge of bariatric surgery, and many reported not seeing women with obesity requiring contraception before (66 %, n = 45) or after surgery (71 %, n = 49). CONCLUSIONS: There is a need to increase knowledge levels of contraception within bariatric surgical teams and to understand why, despite increasing levels of bariatric surgery, women do not seem to be appearing for advice in contraceptive settings.

A randomized controlled trial in non-responders from Newcastle upon Tyne invited to return a self-sample for Human Papillomavirus testing versus repeat invitation for cervical screening.

BACKGROUND: Non-attenders for cervical screening are at increased risk of cervical cancer. Studies offering self-sampling for high-risk Human Papillomavirus (HrHPV) testing have shown greater uptake than sending another invitation for cytology. OBJECTIVES: To explore whether uptake would increase in a less diverse, more stable population than the previous English study, which demonstrated a lower response rate than other studies. The primary objective was whether non-attenders were more likely to respond to a postal invitation, including kit, to collect a self-sample compared with a further invitation for cytology screening. The secondary objective was whether women with an abnormal result would attend for follow-up. METHODS: 6000 non-attenders for screening in this pragmatic, randomized (1:1) controlled trial in Newcastle-upon-Tyne were sent an HPV self-sample kit (intervention) or a further invitation for cytology screening (comparator). RESULTS: 411(13%) responded to the intervention, returning a self-sample (247(8%)) or attending for cytology (164(5%)), compared with 183(6%) attending for cytology, relative risk 2.25 (95% CI 1.90-2.65) (comparator arm). Of those testing hrHPV positive (32(13%)), 19(59%) subsequently attended cytology screening. Of those in the intervention group who attended for cytology screening without returning an hrHPV self-sample (n = 164), 5% (n = 8) were referred for colposcopy - all attended. In the comparator group eight of the nine referred for colposcopy attended. CONCLUSION: Persistent non-responders to invitations for cervical screening are significantly more likely to respond to a postal invitation to return a self-collected sample for HPV testing than a further invitation for cytology screening. However, just over half followed up on this positive HPV result.

The benefits and risks of using a levonorgestrel-releasing intrauterine system for contraception.

The contraceptive profile of the levonorgestrel-releasing intrauterine system (LNG-IUS; Mirena®) is well established, with efficacy similar to that achieved with sterilization and rapid return to fertility after discontinuation of use. The LNG-IUS is typically associated with transient menstrual disturbance during the first few months of use, but this usually settles with continued use, with a concomitant decrease in menstrual blood loss. Overall, the safety profile of the LNG-IUS has been well established across a wide population of women, and the available data do not suggest that the LNG-IUS adversely affects bone health or increase the risk of adverse cardiovascular events or breast and uterine cancers. This article reviews the literature to provide updated information on the risks and benefits associated with the LNG-IUS, particularly focusing on its use in contraception.

Efficacy and tolerability of a monophasic combined oral contraceptive containing nomegestrol acetate and 17ß-oestradiol in a 24/4 regimen, in comparison to an oral contraceptive containing ethinylestradiol and drospirenone in a 21/7 regimen.

OBJECTIVES: The primary objective was to assess the efficacy, cycle control and tolerability of a monophasic combined oral contraceptive (COC) containing nomegestrol acetate (NOMAC) and 17ß-oestradiol (E2). Effects on acne were evaluated as a secondary objective. Results were compared to those of a COC containing drospirenone (DRSP) and ethinylestradiol (EE). METHODS: Women (aged 18-50 years) were randomised to receive NOMAC/E2 (2.5 mg/1.5 mg) in a 24/4-day regimen (n=1591) or DRSP/EE (3 mg/30 µg) in a 21/7-day regimen (n=535) for 13 cycles. RESULTS: Estimated Pearl Indices for NOMAC/E2 and DRSP/EE were 0.38 and 0.81 in women aged≤35 years and 0.31 and 0.66 for all women (18-50 years), respectively. Scheduled withdrawal bleedings were shorter and lighter among users of NOMAC/E2 and were sometimes absent altogether. Intracyclic bleeding/spotting was infrequent in both groups, and decreased over time. Type and frequency of adverse events were similar to those typically reported for COCs. CONCLUSIONS: These data show that NOMAC/E2 provides high contraceptive efficacy with acceptable cycle control as well as an overall adverse event profile similar to that of DRSP/EE.

Bleeding pattern and cycle control with an estradiol-based oral contraceptive: a seven-cycle, randomized comparative trial of estradiol valerate/dienogest and ethinyl estradiol/levonorgestrel.

BACKGROUND: This study compared the bleeding pattern, cycle control and safety of an oral contraceptive (OC) comprising estradiol valerate/dienogest (E2V/DNG; administered using a dynamic dosing regimen) with a monophasic OC containing ethinyl estradiol 20 mcg/levonorgestrel 100 mcg (EE/LNG). E2V releases estradiol (E2), which is identical to endogenously produced 17beta-estradiol. STUDY DESIGN: This was a randomized, multicenter, double-blind, double-dummy trial lasting seven cycles in healthy women aged 18-50 years. RESULTS: Overall, 798 women were randomized and received allocated treatment (399 per group). There were significantly fewer bleeding/spotting days reported by women who received E2V/DNG than those who received EE/LNG [17.3+/-10.4 vs. 21.5+/-8.6, respectively, p<.0001, Reference Period 1 (Days 1-90); and 13.4+/-9.vs. 15.9+/-7.1, respectively, p<.0001, Reference Period 2 (Days 91-180)]. Through Cycles 1-7, the occurrence of scheduled withdrawal bleeding per cycle was 77.7-83.2% with E2V/DNG and 89.5-93.8% with EE/LNG (p<.0001 per cycle). The duration and intensity of scheduled withdrawal bleeding were reduced with E2V/DNG vs. EE/LNG. The incidence of intracyclic bleeding was similar with E2V/DNG (10.5%-18.6%) and EE/LNG (9.9%-17.1%) (p>.05 per cycle). No unintended pregnancies occurred with E2V/DNG, but there was one unintended pregnancy with EE/LNG. Adverse drug reactions occurred in 10.0% and 8.5% of women taking E2V/DNG and EE/LNG, respectively. Overall, 79.4% of women were satisfied with E2V/DNG and 79.9% with EE/LNG. CONCLUSIONS: A novel OC composed of E2V/DNG is associated with an acceptable bleeding profile that is comparable to that of an EE-containing OC.

Provision of contraception services and advice for women with cystic fibrosis.

BACKGROUND AND METHODOLOGY: As the prognosis of patients with cystic fibrosis (CF) improves, issues of sexual health, fertility, pregnancy and contraception are increasingly important. In order to plan the provision of a contraception and sexual health service for women with CF we studied their sexual and reproductive history, their current usage of contraception, the sources and quality of advice they had received, and their particular needs using a confidential questionnaire sent to all women over 16 years of age attending a regional CF centre. RESULTS: Of 55 women (mean age 29.7 years) surveyed, 42 (76%) responded. Thirty-three women (79%) were sexually active and 13 (31%) had experienced 19 pregnancies, five (26%) of which were unplanned. Only half of the women who responded were using contraception. No woman used female sterilisation, the progestogen implant, intrauterine system (IUS) or copper-bearing intrauterine device (IUD) for contraception. Twenty-six (62%) women reported not having received contraceptive advice specific to CF and 24 (57%) said that they had not been warned about the potential interaction between broad-spectrum antibiotics and the combined pill. DISCUSSION: Women with CF have a relatively high rate of unplanned pregnancy and do not receive optimal advice or use the full range of contraceptive methods. CF teams lack training in contraception and contraceptive services may not have a detailed knowledge of CF and its complications. New strategies are needed to focus the knowledge and skills of both teams in providing better services for women with CF.

Women's awareness of long-acting, reversible contraceptive methods (LARCs) in community family planning clinics and general practice.

OBJECTIVES: To investigate whether awareness and choice of long-acting reversible contraceptives (LARCs) of women attending a community family planning clinic differ from those of women seeing general practitioners (GPs). METHODS: Information was collected from women in their reproductive years about their current contraceptive method, their awareness of LARCs and whether they felt well informed about their options. After additional information was provided the respondents were asked whether they would consider changing their method and if their GP offered this option. RESULTS: Questionnaires were completed by 177 women attending a city-centre contraception and sexual health (CASH) clinic (n = 96) and a GP's surgery in a neighbouring city (n = 81). Forty percent of women in the CASH cohort and 6% in the primary care group were using LARCs. Women attending the CASH service were more aware of their contraceptive options and felt better informed but less than 50% in either group had heard of the levonorgestrel-releasing intrauterine system. At least 50% of women would consider using a LARC yet few knew if their GP fitted/provided these methods. CONCLUSION: LARC usage was considerably higher in CASH services compared to primary care. Those providing contraceptive care should give up-to-date information covering all methods and referral to local specialist services, as appropriate.

Modern management of abnormal uterine bleeding: the levonorgestrel intra-uterine system.

Since its launch, more than 9 million women worldwide have used the levonorgestrel intra-uterine system (IUS) for contraception, as a treatment for heavy menstrual bleeding and as the progestogen component of hormone-replacement therapy. For women in their reproductive years, the IUS has become one of the most acceptable medical treatments for menorrhagia, reducing referrals to specialists and decreasing the need for operative gynaecological surgery. This article will outline the development of the IUS, highlighting the most important recent areas of research covering its use to control menstrual blood loss and pain.

A collaborative clinic between contraception and sexual health services and an adult congenital heart disease clinic.

BACKGROUND: The success of cardiac surgery has created a new group of patients: those with 'adult congenital heart disease' (CHD) who may need specialist advice about contraception and pregnancy. The study objective was to investigate whether women with CHD were receiving appropriate advice on contraception. METHODS: The study setting comprised a combined adult CHD and contraception and sexual health clinic operating alongside each other, once a month, at Freeman Hospital, Newcastle-upon-Tyne, UK. Data were collected on 46 consecutive female patients attending the clinic between April 2002 and October 2003. RESULTS: Sixteen of the 46 (35%) women had never discussed contraception with a health professional. Nine of these women were sexually active and were using condoms. Seven of these women chose to start hormonal contraception following consultation. Ten of the 30 (33%) women who had previously discussed contraception with either their general practitioner or family planning clinic had received inappropriate advice. Of these 30 women, 24 needed contraception: 12 (50%) continued with their current method, 10 (42%) started hormonal contraception having previously used either condoms or no contraception and two (8%) changed their current hormonal method to a more effective long-term method (progestogen-only pill to progestogen implant). There had been eight unplanned pregnancies in seven patients. There was poor knowledge among the women about long-acting hormonal methods, particularly progestogen injectables and implants. CONCLUSIONS: Our experience has highlighted the substandard provision of sexual health services for adults with CHD. Many of these women receive either no advice or inappropriate advice about contraception. Suitable effective reversible methods are often denied by health professionals who are concerned about the safety of hormonal contraceptives in women with 'heart problems'. Preconception advice and birth control information should be given to all female patients with CHD, as correct information will avoid the potential risks of an unplanned pregnancy. A monthly regional combined clinic staffed by a cardiologist and family planning doctor provides the ideal opportunity for education of patients and health professionals alike. Good practice is then disseminated across specialities and into the community, encouraging multidisciplinary guidelines and pathways of referral to be developed.

Female sterilisation: is it what women really want?

OBJECTIVE: To audit the effectiveness of a female sterilisation counselling clinic. DESIGN: A prospective, observational study of a female sterilisation counselling clinic over a 6-month period to determine the proportions of attenders keeping their appointment, proceeding to sterilisation, and attending for surgery. SETTING: A hospital-based, city centre family planning clinic run by permanent, family planning-trained staff. RESULTS: A total of 226 women had appointments for female sterilisation counselling and most confirmed attendance. Only 153 (68%) women attended; of those 101 (66%) chose to be sterilised, the remainder choosing reversible contraception. Ninety-three (92%) women went ahead with the sterilisation procedure. Thus only 61% of the original attenders were sterilised; this was only 41% of those referred. CONCLUSIONS: The study suggests that many women referred for sterilisation counselling fail to attend. This finding needs to be further explored. For those women who do attend, accurate information and informed counselling is important. Many women are still unaware of highly effective long-term reversible contraception, and following discussion decide against female sterilisation. Services offering counselling for female sterilisation should also be able to provide easy access to a full range of contraceptive methods.

The 'tail' of a missing intrauterine contraceptive device.

This case presents a cautionary tale demonstrating the importance of skilled ultrasonography for the correct location of an intrauterine device (IUD) lying within the uterine cavity where the threads are 'lost'. Accurate ultrasound examination can ensure the avoidance of unnecessary x-rays or surgery. The case also acts as a reminder that a missing thread of an IUD does not imply that the device is misplaced.