Progesterone from ovulatory menstrual cycles is an important cause of breast cancer.

Many factors, including reproductive hormones, have been linked to a woman's risk of developing breast cancer (BC). We reviewed the literature regarding the relationship between ovulatory menstrual cycles (MCs) and BC risk. Physiological variations in the frequency of MCs and interference with MCs through genetic variations, pathological conditions and or pharmaceutical interventions revealed a strong link between BC risk and the lifetime number of MCs. A substantial reduction in BC risk is observed in situations without MCs. In genetic or transgender situations with normal female breasts and estrogens, but no progesterone (P4), the incidence of BC is very low, suggesting an essential role of P4. During the MC, P4 has a strong proliferative effect on normal breast epithelium, whereas estradiol (E2) has only a minimal effect. The origin of BC has been strongly linked to proliferation associated DNA replication errors, and the repeated stimulation of the breast epithelium by P4 with each MC is likely to impact the epithelial mutational burden. Long-lived cells, such as stem cells, present in the breast epithelium, can carry mutations forward for an extended period of time, and studies show that breast tumors tend to take decades to develop before detection. We therefore postulate that P4 is an important factor in a woman's lifetime risk of developing BC, and that breast tumors arising during hormonal contraception or after menopause, with or without menopausal hormone therapy, are the consequence of the outgrowth of pre-existing neoplastic lesions, eventually stimulated by estrogens and some progestins.

Consensus statement - Urogenital atrophy.

This guidance refers to urogenital atrophy, a chronic and progressive condition due to estrogen deficiency, most commonly associated with the menopause. There is a potential negative impact on all urogenital tissue quality including the vulva, vagina, bladder and urethra. Symptoms may not become apparent for several years after the menopause and therefore any association is lost, with women accepting symptoms as a normal part of the aging process. There may be reluctance to discuss symptoms with a clinician and this is likely to be linked with under diagnosis and under treatment. Urogenital atrophy has been described as a silent epidemic with lack of awareness affecting an accurate diagnosis and access to treatment. Whilst vaginal estrogen (also referred to as local estrogen) therapy is the best-known treatment, newer drugs and interventions are now available.

Urogenital atrophy: The 'unknown factors' challenging current practice.

Urogenital atrophy occurs as a result of the effect of estrogen deficiency on the tissue quality in the vulva, vagina, urethra and bladder. It is a common consequence of the menopause, with possibly up to 80% of women experiencing symptoms. Despite a number of different diagnostic methods, there is no validated objective method by which to confirm the diagnosis in clinical practice and research settings. Education, for women and clinicians, is called for to support diagnosis and treatment. However, before this can be of global benefit, development of an accessible and reproducible diagnostic test is required. Current assessment methods include routine history and clinical examination, with the clinician's opinion based on their subjective observations. A vaginal smear to assess the ratio of superficial to parabasal cells and measurement of the pH of the vaginal secretions is more commonly used in research settings. A number of formulae have been postulated to facilitate the diagnosis including the Vaginal Health Index, the Vulval Health Index, the Genitourinary Syndrome of the Menopause assessment tool, the Genital Health Clinical Evaluation and vaginal biopsy and assessment of the vaginal microbiome. However, none of these potential methods of assessment has been validated. This article focuses on what we do not know about urogenital atrophy including the prevalence, the most appropriate terminology, aetiology, pathogenesis and the most objective and reproducible method of assessment.

A case of endometrial carcinoma in a long-term Levonorgestrel Intrauterine System (LNG 52 mg-IUS) user.

This report describes a 50-year-old woman who presented to a community gynaecology clinic complaining of persistent heavy vaginal bleeding with an LNG 52 mg-IUS in situ. She was subsequently found to have stage 1 grade 1a endometrioid carcinoma. From the literature, we have identified five similar cases. This case highlights the possibility of endometrial carcinoma despite treatment with an LNG 52 mg-IUS and reinforces the importance of investigating women who present with unusual persistent or heavy vaginal bleeding.

Impact of UK Medical Eligibility Criteria implementation on prescribing of combined hormonal contraceptives.

OBJECTIVES: Combined hormonal contraceptives (CHCs) are the most widely prescribed contraceptive methods in the UK; however, their use is associated with significant cardiovascular risk for women with some medical conditions and risk factors. The objective of this study was to assess the potential change in CHC prescribing among higher-risk women following publication of the UK Medical Eligibility Criteria for Contraceptive Use (UKMEC) in 2006. METHODS: A cross-sectional study was conducted using the General Practice Research Database to analyse UK women aged 15-49 years who were prescribed CHCs during the period 2004-2010. Of women prescribed CHCs, those at higher risk of cardiovascular events (with UKMEC Category 3 or 4 risk factors) were identified. The percentage of higher-risk CHC users, among all CHC users, in 2005 (pre-UKMEC) was compared to that in 2010 (post-UKMEC). RESULTS: The percentage of higher-risk CHC users significantly decreased by 0.8% (95% CI 0.68% to 1.02%) following publication of UKMEC [8.1% (95% CI 7.98% to 8.22%) in 2005 vs 7.3% (95% CI 7.14% to 7.38%) in 2010; p<0.001]. However, an estimated 1 74 472 women in the UK were prescribed CHCs in 2010 despite having Category 3 or 4 risk factors. The most common Category 3 or 4 risk factors were body mass index ≥35 kg/m(2), hypertension and smoking in women aged ≥35 years. CONCLUSIONS: Despite the observed reduction in prescribing of CHCs to higher-risk women after publication of UKMEC, a large number of women with Category 3 or 4 risk factors are still prescribed CHCs. The increased risk of cardiovascular events is unnecessary for many of these women given the availability of alternative contraceptive methods.