Counseling on hormone replacement therapy: the real risks and benefits.

PURPOSE OF REVIEW: The menopause transition can be a time of great upheaval and suffering for some patients. Hormone replacement therapy (HRT) can relieve symptoms and improve quality of life but the perceived risks of HRT have decreased use over the past two decades. Understanding the real risks and benefits will ease physician and other healthcare professionals discomfort with counseling and prescribing this potentially life changing therapy in appropriate patients. RECENT FINDINGS: Menopausal symptoms may persist several years beyond the final menstrual period. Previously stated risks of HRT overestimated the concern with menopausal therapy. New data indicates there are medical benefits to HRT beyond quality of life measures. SUMMARY: In appropriate patients, the benefits of hormone replacement therapy outweigh the risks. Extended use of hormone replacement therapy is reasonable in patients with persistent symptoms.

Oestrogen component of COCs: have we finally found a replacement for ethinyl estradiol?

PURPOSE OF REVIEW: Combined oral contraceptive pills are among the most widely used contraceptive methods globally. Despite their popularity, the potential risks and side effects can lead to both high discontinuation rates and adverse outcomes including thromboembolic events. The quest for a safer alternative to the traditional ethinyl estradiol/progestin combination has led to the use of newer oestrogens. Ethinyl oestradiol alternatives will be reviewed including the newest option, estetrol, as it enters clinical use. RECENT FINDINGS: Oestradiol, when combined with a progestin with strong endometrial activity, is a viable alternative to ethinyl estradiol in the form of oestradiol valerate and estradiol, which have been available since 2008 and 2011, respectively. Estetrol is the newest oestrogen available and is found naturally in the foetal liver. Estetrol was approved for use in 2021. All three of these alternatives have high contraceptive efficacy, similar if not improved cycle control and decreased impact on haemostatic factors as compared to ethinyl estradiol. SUMMARY: Alternatives to ethinyl oestradiol, including the newest option of estetrol, show promise in providing comparable contraceptive efficacy with potentially lower risk of side effects and thromboembolic events.

Testosterone Therapy in Women: A Clinical Challenge.

The physiology of testosterone as a normal female hormone in reproductive years and beyond is poorly taught and understood. This has led to unregulated and dangerous prescribing practices by physicians and other health care professionals. There are data for safe use, and as women's health care practitioners, we owe it to our patients to follow these guidelines and practices, as well as advocate for more research and safer, regulated products to prescribe.

Menopause: A Global Perspective and Clinical Guide for Practice.

Perimenopause and menopause are a time of great transition for women-physically, mentally, and emotionally. Symptoms of the menopause transition and beyond impact women worldwide. Unfortunately, physician knowledge and comfort with addressing menopausal concerns vary greatly, limiting the support physicians provide to women in need. This review aims to increase physician understanding of the epidemiology, physiology, symptomology, and treatment options available for perimenopausal and menopausal women. Our goal is to empower physicians to educate and treat their patients to reduce the negative impact of perimenopausal changes and enhance overall well-being for women.

Perimenopausal contraception.

PURPOSE OF REVIEW: Perimenopause is a time of reduced fertility, and yet unintended pregnancies can occur making comprehensive contraceptive counseling essential for these women. Concern over potential contraceptive risks has unnecessarily limited access and use of certain hormonal methods in this population. This review summarizes the available data on the use and effectiveness of contraceptive options during perimenopause. RECENT FINDINGS: All contraceptive options may be appropriate during perimenopause and no method is contraindicated based on age alone. Combined hormonal contraception has the added benefit of relieving perimenopausal symptoms including controlling menstrual irregularities. Progestin-only methods have the advantage of being taken either alone or in combination with estrogen replacement therapy to address both perimenopausal symptoms and contraceptive needs. Nonhormonal options exist for those wishing to avoid hormonal methods. SUMMARY: Extensive contraceptive options are available for perimenopausal women as they transition into menopause. Consideration of patient preference, medical co-morbidities, and perimenopausal symptoms will allow women to use the option that best serves her needs.

Combined hormonal contraception and migraine: are we being too strict?

PURPOSE OF REVIEW: Combined hormonal contraception has been contraindicated in migraines, especially in migraines with aura, because of ischemic stroke risk. Newer formulations are now available and physicians may unnecessarily be limiting access to contraceptive and medical therapeutic options for patients with migraines. This review summarizes the available data regarding ischemic stroke risk of modern combined hormonal contraception in the setting of migraines. RECENT FINDINGS: Limited data exists on current formulations of combined hormonal contraception and outcomes in migraine patients. Studies indicate ischemic stroke risk may be estrogen dose related with high dose formulations having the highest risk. Absolute risk of ischemic stroke with combined hormonal contraception and migraines is low. SUMMARY: Ischemic stroke risk in combined hormonal contraception users in the setting of migraines is low and an individual approach may be more appropriate than current guidelines.

Postpartum intrauterine devices: clinical and programmatic review.

The immediate postpartum period is a critical moment for contraceptive access and an opportunity to initiate long-acting reversible contraception, which includes the insertion of an intrauterine device. The use of the intrauterine device in the postpartum period is a safe practice with few contraindications and many benefits. Although an intrauterine device placed during the postpartum period is more likely to expel compared with one placed at the postpartum visit, women who initiate intrauterine devices at the time of delivery are also more likely to continue to use an intrauterine device compared with women who plan to follow up for an interval intrauterine device insertion. This review will focus on the most recent clinical and programmatic updates on postpartum intrauterine device practice. We discuss postpartum intrauterine device expulsion and continuation, eligibility criteria and contraindications, safety in regards to breastfeeding, and barriers to access. Our aim is to summarize evidence related to postpartum intrauterine devices and encourage those involved in the healthcare system to remove barriers to this worthwhile practice.

Difficult implant removals.

PURPOSE OF REVIEW: Subdermal contraceptive implant insertions have rapidly increased worldwide. These devices are usually removed 3-5 years after insertion. Although removals are generally straightforward, difficult removals can occur. This review discusses the overall approach to potentially problematic removals and the appropriate steps to avoid complications and safely remove implants. RECENT FINDINGS: Given the rapid uptake of contraceptive implants and subsequent need for removals, an Implants Removal Task Force was formed to create standard protocols for difficult implant removals worldwide. These protocols detail how to identify a nonpalpable implant and the subsequent steps needed for safe removals that avoid vascular or neurological complications. SUMMARY: Rapid uptake of subdermal implants has created a need for a comprehensive approach in the unlikely setting of a difficult implant removal. Standard protocols now exist to aid clinicians in the safe removal of these implants.

Long-term culture of human liver tissue with advanced hepatic functions.

A major challenge for studying authentic liver cell function and cell replacement therapies is that primary human hepatocytes rapidly lose their advanced function in conventional, 2-dimensional culture platforms. Here, we describe the fabrication of 3-dimensional hexagonally arrayed lobular human liver tissues inspired by the liver's natural architecture. The engineered liver tissues exhibit key features of advanced differentiation, such as human-specific cytochrome P450-mediated drug metabolism and the ability to support efficient infection with patient-derived inoculums of hepatitis C virus. The tissues permit the assessment of antiviral agents and maintain their advanced functions for over 5 months in culture. This extended functionality enabled the prediction of a fatal human-specific hepatotoxicity caused by fialuridine (FIAU), which had escaped detection by preclinical models and short-term clinical studies. The results obtained with the engineered human liver tissue in this study provide proof-of-concept determination of human-specific drug metabolism, demonstrate the ability to support infection with human hepatitis virus derived from an infected patient and subsequent antiviral drug testing against said infection, and facilitate detection of human-specific drug hepatotoxicity associated with late-onset liver failure. Looking forward, the scalability and biocompatibility of the scaffold are also ideal for future cell replacement therapeutic strategies.