To evaluate contraception use and change among young women with early breast cancer.

Secondary analysis of a cluster randomized trial.

Patients with newly diagnosed breast cancer age ≤45 years enrolled from 54 US oncology practices.

Sites were randomly assigned to the Young Women's Intervention, an educational intervention for young women with newly diagnosed breast cancer and their oncologists addressing issues specific to this population, including contraception, or a contact-time control physical activity intervention. Participants completed surveys in follow-up, including a 3-month survey regarding contraceptive practices before and after diagnosis.

Outcomes of interest included young women's contraceptive use and methods before breast cancer diagnosis and 3 months after study enrollment. Logistic regression models assessed factors associated with use of less than highly effective contraceptive methods categorized according to World Health Organization effectiveness tiers and changes in contraceptive methods.

Of 312 women included, 258 (83%) reported contraceptive use before breast cancer diagnosis, and 275 (88%) reported contraceptive use after diagnosis. Use of highly effective methods (e.g., vasectomy, non-hormonal intrauterine devices) increased from 39% before diagnosis to 52% after diagnosis. Use of moderately effective methods (e.g., hormonal methods) decreased from 22% before diagnosis to 3% after diagnosis. Use of less effective methods (e.g., condoms, withdrawal) increased from 22% before diagnosis to 34% after diagnosis. On multivariable analysis, factors associated with using less than highly effective contraception after diagnosis included desire for additional children (odds ratio [OR], 6.33; 95% confidence interval [CI], 3.76-10.66) and discussing contraception with a provider (OR, 1.96; 95% CI, 1.12-3.40). After breast cancer diagnosis, 207 patients (66%) reported no change in contraceptive methods. On multivariable analysis, factors associated with contraceptive method change after diagnosis included age <35 years (OR, 2.96; 95% CI, 1.57-5.58) and provider discussion (OR, 3.59; 95% CI, 1.91-6.78). There was no association in either analysis with study arm.

Although most patients used contraception after breast cancer diagnosis, nearly half reported using less than highly effective contraceptive methods with higher failure rates, highlighting the need for early and improved contraceptive counseling for young women with breast cancer.

NCT01647607.

Tamoxifen is known to raise the risk of endometrial hyperplasia and cancer. There is virtually limited literature on how to handle Tamoxifen-induced endometrial hyperplasia (EH) in a breast cancer survivor. Levonorgestrel-releasing intrauterine system (LNG-IUS) has been explored as preventive strategies, but its impact on breast cancer recurrence especially in Progesterone receptor (PR)-positive patient is not clear. Aromatase Inhibitors (AIs) have shown beneficial results in EH after tamoxifen and their role should be explored in further trials.

In an effort to switch a norgestrel 0.075 mg progestin-only pill (Opill) from prescription to over-the-counter, we conducted this study to assess whether consumers can use the drug facts label alone to guide appropriate self-selection.

Two studies assessed self-selection: (1) an all-comers, actual-use study evaluating self-selection before purchasing and using norgestrel 0.075 mg and (2) the Targeted Breast Cancer Self-Selection Study evaluating theoretical self-selection among participants with a history of breast cancer.

In the actual-use study, based on the label, 1670/1772 participants (94%) were appropriate for use of norgestrel 0.075 mg; 102 (6%) were not appropriate. Of the 102, 66 (65%) correctly did not select and 36 (35%) responded it was okay for them to use norgestrel 0.075 mg. Of the 36 participants who incorrectly self-selected, one had a history of breast cancer and thus might have been adversely affected had they taken norgestrel 0.075 mg. In the Targeted Breast Cancer Self-Selection Study (N = 206), 97% of participants correctly stated norgestrel 0.075 mg was not appropriate for them.

The proposed over-the-counter label enables 98% of potential users to self-select norgestrel 0.075 mg appropriately. Only 2% of potential purchasers may have bought and started to use norgestrel 0.075 mg inappropriately. For two-thirds of these, the potential benefits of their use of the method outweighed any theoretical risks. Adverse clinical consequences of norgestrel 0.075 mg use are unlikely even in those rare cases when the drug facts label was not followed.

The balance of the risk of inappropriate selection to the benefit of taking an over-the-counter progestin-only pill appears to be very much in favor of an overall benefit in terms of unintended pregnancy prevention.

To compare the prevalence of contraception in breast cancer (BC) patients at risk of unintentional pregnancy (i.e. not currently pregnant or trying to get pregnant) and matched controls.

The FEERIC study (Fertility, Pregnancy, Contraception after BC in France) is a prospective, multicenter case-control study, including localized BC patients aged 18-43 years, matched for age and parity to cancer-free volunteer controls in a 1:2 ratio. Data were collected through online questionnaires completed on the Seintinelles research platform.

In a population of 1278 women at risk of unintentional pregnancy, the prevalence of contraception at study inclusion did not differ significantly between cases (340/431, 78.9%) and controls (666/847, 78.6%, p = 0.97). Contrarily, the contraceptive methods used were significantly different, with a higher proportion of copper IUD use in BC survivors (59.5% versus 25.0% in controls p < 0.001). For patients at risk of unintentional pregnancy, receiving information about chemotherapy-induced ovary damage at BC diagnosis (OR = 2.47 95%CI [ 1.39-4.37] and anti-HER2 treatment (OR = 2.46, 95% CI [ 1.14-6.16]) were significantly associated with the use of a contraception in multivariate analysis.

In this large French study, BC survivors had a prevalence of contraception use similar to that for matched controls, though almost one in five women at risk of unintentional pregnancy did not use contraception. Dedicated consultations at cancer care centers could further improve access to information and contraception counseling.

Meta-analyses have reported conflicting data on the safety of hormonal contraception, but the quality of evidence for the associations between hormonal contraceptive use and adverse health outcomes has not been quantified in aggregate.

To grade the evidence from meta-analyses of randomized clinical trials (RCTs) and cohort studies that assessed the associations between hormonal contraceptive use and adverse health outcomes among women.

MEDLINE, Embase, and the Cochrane Database of Systematic Reviews were searched from database inception to August 2020. Search terms included hormonal contraception, contraceptive agents, progesterone, desogestrel, norethindrone, megestrol, algestone, norprogesterones, and levonorgestrel combined with terms such as systematic review or meta-analysis.

The methodological quality of each meta-analysis was graded using the Assessment of Multiple Systematic Reviews, version 2, which rated quality as critically low, low, moderate, or high. The Grading of Recommendation, Assessment, Development and Evaluations approach was used to assess the certainty of evidence in meta-analyses of RCTs, with evidence graded as very low, low, moderate, or high. Evidence of associations from meta-analyses of cohort studies was ranked according to established criteria as nonsignificant, weak, suggestive, highly suggestive, or convincing.

A total of 2996 records were screened; of those, 310 full-text articles were assessed for eligibility, and 58 articles (13 meta-analyses of RCTs and 45 meta-analyses of cohort studies) were selected for evidence synthesis. Sixty associations were described in meta-analyses of RCTs, and 96 associations were described in meta-analyses of cohort studies. Among meta-analyses of RCTs, 14 of the 60 associations were nominally statistically significant (P ≤ .05); no associations between hormonal contraceptive use and adverse outcomes were supported by high-quality evidence. The association between the use of a levonorgestrel-releasing intrauterine system and reductions in endometrial polyps associated with tamoxifen use (odds ratio [OR], 0.22; 95% CI, 0.13-0.38) was graded as having high-quality evidence, and this evidence ranking was retained in the subgroup analysis. Among meta-analyses of cohort studies, 40 of the 96 associations were nominally statistically significant; however, no associations between hormonal contraceptive use and adverse outcomes were supported by convincing evidence in the primary and subgroup analyses. The risk of venous thromboembolism among those using vs not using oral contraception (OR, 2.42; 95% CI, 1.76-3.32) was initially supported by highly suggestive evidence, but this evidence was downgraded to weak in the sensitivity analysis.

The results of this umbrella review supported preexisting understandings of the risks and benefits associated with hormonal contraceptive use. Overall, the associations between hormonal contraceptive use and cardiovascular risk, cancer risk, and other major adverse health outcomes were not supported by high-quality evidence.

There is a steady global rise in the use of progestin subdermal implants, where use has increased by more than 20 times in the past two decades. BC risk has been reported with the older progestin only methods such as oral pills, injectables, and intrauterine devices, however, little is known about the risk with subdermal implants. In this review, we aim to update clinicians and researchers on the current evidence to support patient counseling and to inform future research directions. The available evidence of the association between the use of progestin subdermal implants and BC risk is discussed. We provide an overview of the potential role of endogenous progesterone in BC development. The chemical structure and molecular targets of synthetic progestins of relevance are summarized together with the preclinical and clinical evidence on their association with BC risk. We review all studies that investigated the action of the specific progestins included in subdermal implants. As well, we discuss the potential effect of the use of subdermal implants in women at increased BC risk, including carriers of BC susceptibility genetic mutations.

Hormone therapy (HT) is an effective treatment for menopausal symptoms, including vasomotor symptoms and genitourinary syndrome of menopause. Randomized trials also demonstrate positive effects on bone health, and age-stratified analyses indicate more favorable effects on coronary heart disease and all-cause mortality in younger women (close proximity to menopause) than in women more than a decade past menopause. In the absence of contraindications or other major comorbidities, recently menopausal women with moderate or severe symptoms are appropriate candidates for HT. The Women's Health Initiative (WHI) hormone therapy trials-estrogen and progestin trial and the estrogen-alone trial-clarified the benefits and risks of HT, including how the results differed by age. A key lesson from the WHI trials, which was unfortunately lost in the posttrial cacophony, was that the risk:benefit ratio and safety profile of HT differed markedly by clinical characteristics of the participants, especially age, time since menopause, and comorbidity status. In the present review of the WHI and other recent HT trials, we aim to provide readers with an improved understanding of the importance of the timing of HT initiation, type and route of administration, and of patient-specific considerations that should be weighed when prescribing HT.

To assess the risk of recurrence with hormonal contraceptive use in breast cancer survivors of reproductive age.

In this retrospective study, women ages 18-51 years who were diagnosed with primary stage 0-3 breast cancer between 2006-2016 and subsequently entered remission were included. Patients with missing information within the cancer registry or electronic medical record and those with a history of hysterectomy and/or sterilization procedure prior to diagnosis were excluded. Hormonal contraception use was defined as being prescribed an oral contraceptive pill (OCP), patch, vaginal ring, medroxyprogesterone injection, etonogestrel implant, or levonorgestrel-releasing intrauterine device (IUD). Women were separated into two groups, hormonal contraceptive users and non-users. Basic descriptive and inferential statistics were used to compare groups as appropriate. The primary outcome reviewed was local or distant breast cancer recurrence. Secondary outcomes included all-cause mortality and pregnancy.

Following exclusions, 1370 women remained in the cohort. Ninety-seven women (7.08 %) received a prescription for a form of hormonal contraception. When comparing groups, hormonal contraceptive users were more likely to be between 18-40 years of age (46.39 % vs. 17.99 % non-users;P < 0.01) and never smokers (68.04 % vs. 38.57 % non-users; P < 0.01). Patients did not differ between groups based on any other demographic or cancer-related characteristic, including tumor hormone receptor expression. Overall, 92 patients (6.72 %) experienced local or distant recurrence during the study period. Recurrence did not differ between groups (6.19 % users vs. 6.76 % non-users; P = 0.83). All-cause mortality and pregnancy rates also did not differ between hormonal contraceptive users and non-users.

The study shows no increased risk of recurrence associated with hormonal contraceptive use after breast cancer diagnosis and remission.

Adjuvant tamoxifen reduces the risk of breast cancer recurrence in women with oestrogen receptor-positive breast cancer. Tamoxifen also increases the risk of postmenopausal bleeding, endometrial polyps, hyperplasia, and endometrial cancer. The levonorgestrel-releasing intrauterine system (LNG-IUS) causes profound endometrial suppression. This systematic review considered the evidence that the LNG-IUS prevents the development of endometrial pathology in women taking tamoxifen as adjuvant endocrine therapy for breast cancer.

To determine the effectiveness and safety of the levonorgestrel intrauterine system (LNG-IUS) in pre- and postmenopausal women taking adjuvant tamoxifen following breast cancer for the outcomes of endometrial and uterine pathology including abnormal vaginal bleeding or spotting, and secondary breast cancer events.

We searched the following databases on 29 June 2020; The Cochrane Gynaecology and Fertility Group specialised register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase, PsycINFO and Cumulative Index to Nursing and Allied Health Literature. We searched the Cochrane Breast Cancer Group specialised register on 4 March 2020. We also searched two trials registers, checked references for relevant trials and contacted study authors and experts in the field to identify additional studies.

We included randomised controlled trials (RCTs) of women with breast cancer on adjuvant tamoxifen that compared the effectiveness of the LNG-IUS with endometrial surveillance versus endometrial surveillance alone on the incidence of endometrial pathology.

We used standard methodological procedures recommended by Cochrane. The primary outcome measure was endometrial pathology (including polyps, endometrial hyperplasia, or endometrial cancer), diagnosed at hysteroscopy or endometrial biopsy. Secondary outcome measures included fibroids, abnormal vaginal bleeding or spotting, breast cancer recurrence, and breast cancer-related deaths. We rated the overall certainty of evidence using GRADE methods.

We included four RCTs (543 women analysed) in this review. We judged the certainty of the evidence to be moderate for all of the outcomes, due to imprecision (i.e. limited sample sizes and low event rates). In the included studies, the active treatment arm was the 20 μg/day LNG-IUS plus endometrial surveillance; the control arm was endometrial surveillance alone. In tamoxifen users, the LNG-IUS probably reduces the incidence of endometrial polyps compared to the control group over both a 12-month period (Peto odds ratio (OR) 0.22, 95% confidence interval (CI) 0.08 to 0.64, I² = 0%; 2 RCTs, n = 212; moderate-certainty evidence) and over a long-term follow-up period (24 to 60 months) (Peto OR 0.22, 95% CI 0.13 to 0.39; I² = 0%; 4 RCTs, n = 417; moderate-certainty evidence). For long-term follow-up, this suggests that if the incidence of endometrial polyps following endometrial surveillance alone is assumed to be 23.5%, the incidence following LNG-IUS with endometrial surveillance would be between 3.8% and 10.7%.  The LNG-IUS probably slightly reduces the incidence of endometrial hyperplasia compared with controls over a long-term follow-up period (24 to 60 months) (Peto OR 0.13, 95% CI 0.03 to 0.67; I² = 0%; 4 RCTs, n = 417; moderate-certainty evidence). This suggests that if the chance of endometrial hyperplasia following endometrial surveillance alone is assumed to be 2.8%, the chance following LNG-IUS with endometrial surveillance would be between 0.1% and 1.9%. However, it should be noted that there were only six cases of endometrial hyperplasia. There was insufficient evidence to reach a conclusion regarding the incidence of endometrial cancer in tamoxifen users, as no studies reported cases of endometrial cancer. At 12 months of follow-up, the LNG-IUS probably increases abnormal vaginal bleeding or spotting compared to the control group (Peto OR 7.26, 95% CI 3.37 to 15.66; I² = 0%; 3 RCTs, n = 376; moderate-certainty evidence). This suggests that if the chance of abnormal vaginal bleeding or spotting following endometrial surveillance alone is assumed to be 1.7%, the chance following LNG-IUS with endometrial surveillance would be between 5.6% and 21.5%. By 24 months of follow-up, abnormal vaginal bleeding or spotting occurs less frequently than at 12 months of follow-up, but is still more common in the LNG-IUS group than the control group (Peto OR 2.72, 95% CI 1.04 to 7.10; I² = 0%; 2 RCTs, n = 233; moderate-certainty evidence). This suggests that if the chance of abnormal vaginal bleeding or spotting following endometrial surveillance alone is assumed to be 4.2%, the chance following LNG-IUS with endometrial surveillance would be between 4.4% and 23.9%. By 60 months of follow-up, there were no cases of abnormal vaginal bleeding or spotting in either group. The numbers of events for the following outcomes were low: fibroids (n = 13), breast cancer recurrence (n = 18), and breast cancer-related deaths (n = 16). As a result, there is probably little or no difference in these outcomes between the LNG-IUS treatment group and the control group.  AUTHORS' CONCLUSIONS: The LNG-IUS probably slightly reduces the incidence of benign endometrial polyps and endometrial hyperplasia in women with breast cancer taking tamoxifen. At 12 and 24 months of follow-up, the LNG-IUS probably increases abnormal vaginal bleeding or spotting among women in the treatment group compared to those in the control. Data were lacking on whether the LNG-IUS prevents endometrial cancer in these women. There is no clear evidence from the available RCTs that the LNG-IUS affects the risk of breast cancer recurrence or breast cancer-related deaths. Larger studies are necessary to assess the effects of the LNG-IUS on the incidence of endometrial cancer, and to determine whether the LNG-IUS might have an impact on the risk of secondary breast cancer events.

Safety of pregnancy occurring after breast cancer treatment has been studied largely, but it is still debatable. These studies have generally showed that overall and disease-free survival in breast cancer survivors with subsequent pregnancy is not less than those without future pregnancy . Also, breast cancer survivors treated with chemotherapy , radiation therapy, or both had no increased risk of congenital anomalies, single gene disorders, or chromosomal syndromes in their offspring. However, it appears that the incidence of preterm labor, low birth weight, and fetal anomalies is higher in these cases.These issues as well as safe time interval from breast cancer treatment to pregnancy , safe contraceptive method after breast cancer, counseling about pregnancy in survivors, and how to follow up the patient for breast cancer recurrence during pregnancy are discussed in this chapter.

Pregnancy associated breast cancer (PABC) defined as breast cancer occurring during pregnancy or within the first 1-2 years postpartum. Delay in diagnosis is common. Treatment is timed around gestational age. Surgery and chemotherapy are considered safe after the first trimester. Radiation, anti-her-2, and endocrine therapy are delayed until after delivery due to adverse fetal effects. Iatrogenic prematurity likely causes most long-term fetal sequelae. Multi-disciplinary care and social support are critical for patients and families with PABC.

Although numerous studies have addressed the safety and effectiveness of hormonal contraceptive use in healthy women, data regarding women with underlying medical conditions or other special circumstances are limited. The U.S. Medical Eligibility Criteria (USMEC) for Contraceptive Use, 2016 (), which has been endorsed by the American College of Obstetricians and Gynecologists, is a published guideline based on the best available evidence and expert opinion to help health care providers better care for women with chronic medical problems who need contraception. The goal of this Practice Bulletin is to explain how to use the USMEC rating system in clinical practice and to specifically discuss the rationale behind the ratings for various medical conditions. Contraception for women with human immunodeficiency virus (HIV) (); the use of emergency contraception in women with medical coexisting medical conditions, including obesity, (); and the effect of depot medroxyprogesterone acetate (DMPA) on bone health () are addressed in other documents from the American College of Obstetricians and Gynecologists.

Objective: The efficacy of treatment for many cancers has increased dramatically in recent decades and there are a growing number of cancer survivors who need effective contraception. In this paper, a group of experts from the European Society of Contraception set out to define the most frequent cancers in women and summarise the guidelines, reviews and studies that provide information and guidance on contraception for each cancer. Methods: Epidemiological studies were analysed to determine the frequency of cancers in women of reproductive age. A narrative review was performed for each cancer, collecting data about the treatment of the disease, its impact on fertility, and the efficacy, health risks, possible benefits and contraindications of the contraceptive methods available. The recommendations were then summarised. Results: Owing to a large amount of information, the results are presented in two parts. Part 1 includes contraception after breast and gynaecological cancers. Part 2 summarises the findings and recommendations regarding contraception in women with skin, gastrointestinal, haematological and endocrine cancers.

To synthesize knowledge on cancer risks related to hormonal contraception and to propose recommendations on contraception during treatment and after cancer.

A systematic review of the literature about hormonal contraception and cancer was conducted on PubMed/Medline and the Cochrane Library.

Overall, there is no increase in cancer (all types together) incidence or mortality among hormonal contraceptive users. Estroprogestin combined contraceptive use is associated with an increased risk of breast cancer (during use), and with a reduced risk of endometrial, ovarian, lymphatic or hematopoietic cancers that persist after discontinuation, and a decreased risk of colorectal cancer. Information on cancer risk is part of the systematic information given to patients wishing contraception. However, these data will not influence its prescription, considering the positive risk/benefit balance in women without specific cancer risk factor. Contraception is required during and after cancer treatment in every non-menopausal woman at cancer diagnosis. Specific thromboembolic, immunologic or vomiting risks due to the oncological context should be taken into account before the contraceptive choice. All hormonal contraceptives are contra-indicated after breast cancer, regardless of the delay since treatment, hormone receptor status and histological subtype. There is no data in the literature to limit hormonal or non-hormonal contraceptive use after colorectal or thyroid cancer. There was insufficient data in the literature to propose recommendations on contraceptive choice after cervical cancer, melanoma, lung cancer, tumor of the central nervous system, or after thoracic irradiation. If an emergency contraception is needed in a woman previously treated for a hormone-sensitive cancer, a non-hormonal copper intrauterine device should be preferred.

Information on cancer risk is part of the patient's information but does not influence the prescription of contraception in the absence of any specific risk factor. Contraception should be proposed in every woman treated or previously treated for cancer. The whole context should be taken into account to choose a tailored contraception.

The improved detection and successful treatment of breast cancer, resulting in better survival rates, has led to an increasing number of women living with the effects of treatment modalities and their long-term consequences. Menopausal symptoms following breast cancer can occur at an earlier age, be more severe and significantly influence a woman's overall wellbeing, in particular, sexual function, quality of life and adherence to treatment. There is a dearth of good quality evidence on the safest and most effective treatment options available for these women, and this article aims to summarize the current available treatments. Pertinent to these women is general advice, such as avoidance of triggers, and lifestyle modifications. Following which, non-pharmacological interventions, including cognitive behavior therapy (CBT), hypnosis, acupuncture, stellate ganglion nerve block and complementary agents, are discussed. Pharmacological therapies and their safety profile in these high-risk women are then examined; namely, menopausal hormone therapy, progestogens, antidepressants (selective serotonin reuptake inhibitors and selective noradrenaline reuptake inhibitors), gabapentin, clonidine and intra-vaginal dehydroepiandrosterone (DHEA). Finally, neurokinin 3 receptor antagonists, promising new agents for the treatment of troublesome menopausal vasomotor symptoms, are discussed.

Most women use hormonal contraception for more than 30 years and for many, this may involve exposure in their older reproductive years when baseline breast cancer risk rises steeply. Overall, the risk of breast cancer diagnosis with exposure to hormonal contraception is very small and outweighed by its contraceptive benefits but despite this, there are still outstanding questions for all methods used in clinical practice due to paucity of available evidence, lack of which should not be taken to imply safety. This is exemplified by the following assumptions: the progestogen-only pill and long-acting reversible contraceptives are 'breast-safe' options in peri-menopausal women, use of the levonorgestrel intrauterine system for the management of endometrial pathology in breast cancer survivors is less likely to promote disease recurrence and the benefit all hormonal contraceptive methods confer in reducing unplanned pregnancy in women at high familial risk outweigh the risk of breast cancer diagnosis. There is no data on risk with the concurrent prescription of hormone replacement therapy in women exhibiting climacteric symptoms who are still menstruating. Advice of GPs and Community Sexual & Reproductive Health specialists will inevitably be sought about some or all these issues and in the absence of conclusive evidence from clinical studies, caution should be applied and women counselled appropriately.

Patients not older than 40 years are referred to as young patients. These women benefit from chemo-, endocrine and anti-HER2 therapy to a similar degree as older women. Surgery and radiation therapy also follow the same recommendations. This manuscript deals with the following topics that need special consideration in young women: endocrine therapy and ovarian suppression; fertility protection and family planning; and genetic counselling. There is an on-going debate on whether tamoxifen is sufficient as an endocrine treatment in young patients with endocrine-responsive tumours or whether suppression of ovarian function in combination with tamoxifen or aromatase inhibitor should be preferred. Recent data suggest a benefit from ovarian suppression plus exemestane in women of 35 years or younger with high-risk breast cancer. However, increased side effects bear the risk of lesser compliance, which eventually results in higher mortality. Child bearing is nowadays frequently postponed to the 4th decade of life, thereby increasing the number of women who have not yet finished their reproductive desires when diagnosed with breast cancer. These patients are in urgent need of counselling for fertility protection. Breast cancer diagnosis at young age is an indication for a possible mutation in breast cancer susceptibility genes. This has an impact on the cancer risk of the whole family, especially the offspring. Drugs that are specifically targeted to cancer cells with genetic alterations that impair DNA repair are already entering the arsenal of oncologists.

Adjuvant tamoxifen reduces the risk of breast cancer recurrence in women with oestrogen receptor-positive breast cancer. Tamoxifen also increases the risk of postmenopausal bleeding, endometrial polyps, hyperplasia, and endometrial cancer. The levonorgestrel-releasing intrauterine system (LNG-IUS) causes profound endometrial suppression. This systematic review considered the evidence that the LNG-IUS prevents the development of endometrial pathology in women taking tamoxifen as adjuvant endocrine therapy for breast cancer.

To determine the effectiveness and safety of levonorgestrel intrauterine system (LNG-IUS) in pre- and postmenopausal women taking adjuvant tamoxifen following breast cancer for the outcomes of endometrial and uterine pathology including abnormal vaginal bleeding or spotting, and secondary breast cancer events.

We searched the following databases: Cochrane Menstrual Disorders and Subfertility Group Specialised Register (MDSG), Cochrane Breast Cancer Group Specialised Register (CBCG), Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Abstracts of Reviews of Effects (DARE), The Cochrane Library, clinicaltrials.gov, The World Health Organisation International Trials Registry, ProQuest Dissertations & Theses, MEDLINE, EMBASE, CINAHL (Cumulative Index to Nursing and Allied Health Literature), PsycINFO, Web of Science, OpenGrey, LILACS, PubMed, and Google. The final search was performed in October 2015.

Randomised controlled trials of women with breast cancer on adjuvant tamoxifen that compared endometrial surveillance alone (control condition) versus the LNG-IUS with endometrial surveillance (experimental condition) on the incidence of endometrial pathology.

Study selection, risk of bias assessment and data extraction were performed independently by two review authors. The primary outcome measure was endometrial pathology (including polyps, endometrial hyperplasia, or endometrial cancer) diagnosed at hysteroscopy or endometrial biopsy. Secondary outcome measures included fibroids, abnormal vaginal bleeding or spotting, breast cancer recurrence, and breast cancer-related deaths. The overall quality of evidence was rated using GRADE methods.

Four randomised controlled trials involving 543 women were identified and are included in this review. In the included studies, the active treatment arm was the 20 μg/day levonorgestrel-releasing intrauterine system (LNG-IUS) plus endometrial surveillance; the control arm was endometrial surveillance alone. In tamoxifen users, the LNG-IUS led to a reduction in the incidence of endometrial polyps over both a 12-month period (Peto OR 0.22, 95% CI 0.08 to 0.64, 2 studies, n = 212, I² = 0%) and over a long-term follow-up period (24 to 60 months) (Peto OR 0.22, 95% CI 0.13 to 0.39, 4 studies, n = 417, I² = 0%, moderate quality evidence). Also the LNG-IUS led to a reduction in the incidence of endometrial hyperplasia over a long-term follow-up period (24 to 60 months) (Peto OR 0.13, 95% CI 0.03 to 0.67, four studies, n = 417, I² = 0%, moderate quality evidence). However, it should be noted that the number of events of endometrial hyperplasia was low (n = 6). None of the trials were sufficiently powered to detect whether LNG-IUS leads to significant changes in the incidence of endometrial cancer in tamoxifen users. At 12 months of follow-up abnormal vaginal bleeding or spotting was more common in the LNG-IUS treatment group (Peto OR 7.26, 95% CI 3.37 to 15.66, 3 studies, n = 376, I² = 0%, moderate quality evidence). By 24 months of follow-up, abnormal vaginal bleeding or spotting occurred less frequently compared to 12 months of follow-up in the LNG-IUS treatment group but was still more common than the control group (Peto OR 2.72, 95% CI 1.04 to 7.10, 2 studies, n = 233, I² = 0%, moderate quality evidence). By 60 months of follow-up, no cases of abnormal vaginal bleeding or spotting were reported in either group. The numbers of events for the following outcomes were low: fibroids (n = 13), breast cancer recurrence (n = 18), and breast cancer-related deaths (n = 16). There was no evidence of a difference between the LNG-IUS treatment group and controls for these outcomes. The quality of the evidence was judged as moderate, due to limited sample sizes and low event rates for the outcome comparisons.

The LNG-IUS reduces the incidence of benign endometrial polyps and endometrial hyperplasia in women with breast cancer taking tamoxifen. At 12 and 24 months of follow-up, the LNG-IUS increased abnormal vaginal bleeding or spotting among women in the treatment group compared to those in the control. There is no clear evidence from the available randomised controlled trials that the LNG-IUS prevents endometrial cancer in these women. There is no clear evidence from the available randomised controlled trials that the LNG-IUS affects the risk of breast cancer recurrence or breast cancer-related deaths. Larger studies are necessary to assess the effects of the LNG-IUS on the incidence of endometrial cancer, and to determine whether the LNG-IUS might have an impact on the risk of secondary breast cancer events.

This literature review focuses on contraception in perimenopausal women. As women age, their fecundity decreases but does not disappear until menopause. After age 40, 75% of pregnancies are unplanned and may result in profound physical and emotional impact. Clinical evaluation must be relied on to diagnose menopause, since hormonal levels fluctuate widely. Until menopause is confirmed, some potential for pregnancy remains; at age 45, women's sterility rate is 55%. Older gravidas experience higher rates of diabetes, hypertension, and death. Many safe and effective contraceptive options are available to perimenopausal women. In addition to preventing an unplanned and higher-risk pregnancy, perimenopausal contraception may improve abnormal uterine bleeding, hot flashes, and menstrual migraines. Long-acting reversible contraceptives, including the levonorgestrel intrauterine system (LNG-IUS), the etonogestrel subdermal implant (ESI), and the copper intrauterine device (Cu-IUD), provide high efficacy without estrogen. LNG-IUS markedly decreases menorrhagia commonly seen in perimenopause. Both ESI and LNG-IUS provide endometrial protection for women using estrogen for vasomotor symptoms. Women without cardiovascular risk factors can safely use combined hormonal contraception. The CDC's Medical Eligibility Criteria for Contraceptive Use informs choices for women with comorbidities. No medical contraindications exist for levonorgestrel emergency-contraceptive pills, though obesity does decrease efficacy. In contrast, the Cu-IUD provides reliable emergency and ongoing contraception regardless of body mass index (BMI).

To estimate the rate of endometrial pathology with the prophylactic use of levonorgestrel-releasing intrauterine system in women with breast cancer treated with tamoxifen.

This was a randomized contro-lled trial of 129 Chinese women who attended a university hospital in Hong Kong and required adjuvant tamoxifen for breast cancer after the completion of postoperative radiotherapy and chemotherapy. Women were randomized to treatment (prophylactic levonorgestrel-releasing intrauterine system insertion before the commencement of tamoxifen) or control group. The uterine cavity was examined by hysteroscopy and endometrial sampling before the commencement of tamoxifen and at 12, 24, 45, and 60 months afterward. Any endometrial polyps or submucosal fibroids were resected through hysteroscopy at each assessment and specimens were sent for histologic confirmation.

A total of 94 women completed 5-year follow-up. There was no significant difference in the occurrence of submucosal fibroids (1 [1.8%] compared with 2 [3.4%]) and endometrial hyperplasia (both 0) in the treatment and control groups, respectively. Levonorgestrel-releasing intrauterine system significantly reduced de novo endometrial polyps (hazard ratio 0.19, 95% confidence interval 0.07-0.48) over the course of 5 years on an intention-to-treat basis. There was no statistically significant increase in breast cancer recurrence rate (10 [17.2%] compared with 6 [10.0%]) or cancer-related deaths (6 [10.3%] compared with 5 [8.3%]) in the treatment group, but the study was underpowered in this regard.

Prophylactic levonorgestrel-releasing intrauterine system prevents de novo endometrial polyps in women using tamoxifen. However, its role in the prevention of endometrial hyperplasia and adenocarcinoma as well as its effect on risk of breast cancer recurrence remain uncertain.

Chinese Clinical Trial Registry, http://www.chictr.org/en/, ChiCTR-TRC-09000625.

I.

Norgestrel, a synthetic progestin chemically derived from 19-nortestosterone, is six times more potent than progesterone, with variable binding affinity to various steroid receptors. The levonorgestrel-releasing intrauterine system (LNG IUS) provides a long-acting, highly effective, and reversible form of contraception, with a pearl index of 0.18 per 100 women-years. The locally released hormone leads to endometrial concentrations that are 200-800 times those found after daily oral use and a plasma level that is lower than that with other forms of levonorgestrel-containing contraception. The contraceptive effect of the LNG IUS is achieved mainly through its local suppressive effect on the endometrium, leading to endometrial thinning, glandular atrophy, and stromal decidualization without affecting ovulation. The LNG IUS is generally well tolerated. The main side effects are related to its androgenic activity, which is usually mild and transient, resolving after the first few months. Menstrual abnormalities are also common but well tolerated, and even become desirable (eg, amenorrhea, hypomenorrhea, and oligomenorrhea) with proper counseling of the patient during the choice of the method of contraception. The satisfaction rates after 3 years of insertion are high, reaching between 77% and 94%. The local effect of the LNG IUS on the endometrium and low rates of systemic adverse effects have led to its use in other conditions rather than contraception, as for the treatment of endometrial hyperplasia, benign menorrhagia, endometriosis, adenomyosis, and uterine fibroids.

More women are diagnosed and treated for breast cancer today than at any time in the past. New technologies in the treatment of breast cancer and breast reconstruction are changing morbidity and mortality realities for women diagnosed with breast cancer. Primary care providers in women's health care can provide valuable support, education, and advocacy for their clients who are dealing with breast cancer. This article reviews current breast cancer treatment guidelines, information on breast reconstruction after cancer, and primary care recommendations for post-breast cancer care.

In recent years, intrauterine contraception has experienced a revival, explainable as much by the broadening of its indications as by the ever increasing demand, expressed by women, for a contraceptive method that is both reliable and not binding. In this review, we establish an up-to-date and comprehensive state of intrauterine contraception in 2010, by responding to key-questions, which arise from everyday practice in gynaecology.

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.

To give an overview about current treatment recommendations and special problems concerning the management of women <35 years with early breast cancer.

We performed a selective systematic literature review. We discussed with reference to key studies and meta-analyses, current standards of care, and controversies regarding patient management.

Breast cancer in patients younger than 35 years is rare but associated with an unsatisfactory prognosis. Local treatment should not differ from general guidelines, but awareness of the high risk of local recurrence must be maintained. Adjuvant polychemotherapy is almost always indicated, standard endocrine therapy is tamoxifen. Before the start of systemic therapy, the patient must be offered different types of fertility preservation. Pregnancy related breast cancer is not associated with a worse prognosis, but with delayed diagnosis. Therefore, every suspicious lesion in the breast or axilla must be imaged and biopsied. The optimal time to delay pregnancy following the diagnosis is unknown. Hormonal contraceptives are contraindicated after breast cancer. Every woman <35 years diagnosed with breast cancer should be offered genetic counseling.

The management of breast cancer in very young women requires a multidisciplinary team to find the optimal treatment and to solve their specific problems.

Premenopausal women with a new diagnosis of breast cancer are faced with many challenges. Providing health care for issues such as gynecologic comorbidities, reproductive health concerns, and vasomotor symptom control can be complicated because of the risks of hormone treatments and the adverse effects of adjuvant therapies. It is paramount that health care professionals understand and be knowledgeable about hormonal and nonhormonal treatments and their pharmacological parameters so they can offer appropriate care to women who have breast cancer, with the goal of improving quality of life. Articles for this review were identified by searching the PubMed database with no date limitations. The following search terms were used: abnormal uterine bleeding, physiologic sex steroids, endometrial ablation, hysteroscopic sterilization, fertility preservation in endometrial cancer, tranexamic acid and breast cancer, menorrhagia treatment and breast cancer, abnormal uterine bleeding and premenopausal breast cancer, levonorgestrel IUD and breast cancer, tamoxifen and gynecologic abnormalities, tamoxifen metabolism, hormones and breast cancer risk, contraception and breast cancer, pregnancy and breast cancer, and breast cancer and infertility treatment.

Recent clinical trials show that combined oral dosing with estrogen and progestin increases the incidence of breast cancer in postmenopausal women. Similarly, in a rat model system of mammary carcinogenesis, the synthetic progestin medroxyprogesterone acetate (MPA) decreases latency and increases incidence of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors. The goal of this study was to compare the effects of four clinically relevant progestins, MPA, norgestrel (N-EL), norethindrone (N-ONE), and megestrol acetate (MGA), on DMBA-induced mammary carcinogenesis in the rat. The experimental protocol involved implantation of 60-day release progestin pellets four weeks after rats were treated with DMBA. In contrast to the effect of MPA, N-ONE, and N-EL, but not MGA, blocked DMBA-dependent carcinogenesis and a dose-dependent effect on tumor growth was shown for N-EL; MGA did not alter tumor growth. Histopathologic studies showed extensive hyperplastic lesions in mammary tissue of progestin-treated animals. Furthermore, following treatment with N-EL or N-ONE, immunohistochemical staining for vascular endothelial growth factor in hyperplastic mammary tissue was lower than in animals treated with DMBA plus MPA or DMBA alone. Expression of vascular endothelial growth factor receptor-1, estrogen receptor alpha, and progesterone receptor was also lower in hyperplastic mammary tissue in N-EL-, N-ONE-, and MGA-treated animals. Interestingly, N-EL stimulated progression of existing mammary tumors in DMBA/MPA-treated rats, suggesting stage-specific effects of N-EL in this model. Because N-EL and N-ONE prevent tumor growth in the early stages of DMBA-induced mammary carcinogenesis in rats, these progestins may have potential as chemopreventive agents in women with no history of breast disease or family history of breast cancer.

Approximately 12 million women worldwide use the levonorgestrel-releasing intrauterine system (IUS), with approximately 180,000 users of this IUS currently reported in Austria. A patient satisfaction study of 591 women in Austria revealed a high number of 'very satisfied' (79%) and 'satisfied' (19%) patients. Reliability, comfort, excellent compatibility and less severe, shorter and less painful monthly periods were the most frequently named advantages of the levonorgestrel-releasing IUS. Medication-induced cervical priming before insertion can be carried out on a routine or selective basis (for example in nullipara, in women who have undergone cervical conisation or in women who have previously experienced painful insertion). There is, at present, no evidence of an increased rate of breast cancer through use of the levonorgestrel-releasing IUS. A directly comparative study with oral contraceptives in young nullipara showed excellent results for the levonorgestrel-releasing IUS, with no perforations, inflammation or pregnancies.

Women who have survived cancer may need guidance in choosing a method of contraception. This paper reviews the evidence supporting the safety and efficacy of available methods of contraception for cancer survivors and concludes that the Copper T380A intrauterine device (IUD), a highly effective, reversible, long-acting, hormone-free method should be considered a first-line contraceptive option for women with a history of a hormonally mediated cancer. However, the levonorgestrel-containing IUD may be preferable for women being treated with tamoxifen and women who have survived non-hormonally mediated cancers. Women with IUDs can undergo all forms of imaging, including computed tomography and magnetic resonance imaging.