Seminars in reproductive medicine最新文献

Progestogens (norethisterone acetate, medroxyprogesterone acetate, dydrogesterone, micronized progesterone, levonorgestrel, drospirenone, and trimegestone) added to estrogen for endometrial protection are reviewed. They can be given orally or vaginally, norethisterone acetate can also be given transdermally, and levonorgestrel can be given through the intrauterine route. Sequential use of progestogens protects the endometrium if exposure lasts for at least 12 days/month; longer intervals are not safe. Continuous use of progestogens, whether oral, transdermal, or intrauterine, provides the most effective protection. Progestogen addition is accompanied with significant elevations in breast cancer risk, the largest drawback of progestogen use, and dydrogesterone, micronized progesterone, and a levonorgestrel intrauterine device may be safest in this regard. Progestogens also double deep vein thrombosis risk and diminish the positive effect of estrogen on colorectal cancer and vascular health. Recent data imply a neutral effect of progestogens in combination with estrogen on Alzheimer's disease risk, but the risk of vascular dementia is decreased. In conclusion, progestogens are a double-edged sword, effectively protecting the endometrium but causing several side effects and reducing many estrogen-induced benefits. With modern endometrial diagnostic tools, the safety of low-dose unopposed estrogen regimens should be assessed in a prospective controlled trial in women with an intact uterus.

Although the average age of menopause in western women is 50 years, 10% of women experience menopause between the age of 40 and 44 (early menopause) and 2 to 3% before the age of 40 (premature ovarian insufficiency). Although the etiology of early-onset menopause varies, it remains unknown in most cases. The most common reasons are genetic factors or chromosomal abnormalities, cancer treatment, bilateral oophorectomy, and autoimmune diseases. Early or premature menopause can negatively impact a woman's long-term health. There is strong evidence that these conditions increase the risk of osteoporosis, cardiovascular disease (CVD) morbidity, and premature mortality. There is comparatively little evidence, however, on other associated health risks or on their potential for mitigation by hormone replacement therapy (HRT). In this review, we examine the literature on the long-term health of women with early-onset menopause, particularly its effects on morbidity, mortality, and quality of life. At-risk women and their physicians should be aware of the age-related risks of menopause to avoid or mitigate negative outcomes.

Menopause represents a cardio-metabolic transition, but cardiovascular (CV) health in women is highly influenced by other reproductive milestones and conditions, which delineate a cardio-reproductive lifeline. Reproductive history represents an opportunity to identify women at elevated risk of CV events after menopause, going beyond traditional CV risk factors. This review aims to summarize the impact of reproductive milestones, gynecological conditions, and pregnancy-related factors on cardio-metabolic health at midlife. The main physio-pathological mechanisms likely implicated in linking reproductive events and CV disease risk are described, as well as the impact of specific conditions (early/late menarche and menstrual dysfunction [functional hypothalamic amenorrhea, polycystic ovary syndrome, benign gynecological conditions (endometriosis, adenomyosis, and fibroids), infertility, adverse pregnancy outcomes, and premature/early natural or surgical menopause]). Data indicate that a reproductive checklist in midlife women is warranted for primary prevention and intervention.

Estrogens, including estradiol and estrone, and androgens, including testosterone, are locally produced in adipose tissue throughout a woman's lifespan. Already in fertile-aged women, subcutaneous and visceral adipose tissue produce notable amounts of estrogens despite ongoing ovarian estrogen synthesis. After menopause, adipose tissue becomes the most important producer of estrogens. A decrease in circulating estrogen concentrations coincides with a relative increase in the amount of visceral adipose tissue and an increased risk for metabolic disorders. Furthermore, local adipose tissue biosynthesis of sex steroids may regulate the distribution of adipose tissue between the subcutaneous and visceral depots. Further studies are needed to characterize the relation of local adipose tissue sex steroid milieu to local and circulating markers of adipose tissue and metabolic dysfunction. This can shed more light on the increasing adiposity and metabolic burden associated with menopause. Here, we discuss the roles estrogens and androgens play in adipose tissue distribution and function before and after menopause, and highlight the role of local sex steroid biosynthesis, or intracrinology, in determining local tissue sex steroid environments.

Perimenopausal women have specific needs when it comes to contraception. Although fertility rates generally decrease after age 40, pregnancy is still possible and may be associated with a higher risk of obstetric and fetal complications. Moreover, women may experience bothersome symptoms during perimenopause due to anovulatory cycles and fluctuating estrogen levels, such as abnormal uterine bleeding, vasomotor symptoms, migraines, and mood disorders. Additionally, age increases the risk of the most common side effects of well-known contraceptives, particularly those containing estrogen. For this reason, contraception counseling during perimenopause should be tailored to the woman's characteristics. It should include three steps: evaluating the woman's needs and symptoms; evaluating the potential benefits of the chosen method; evaluating risk factors that may contraindicate certain choices. No contraceptive method is contraindicated solely based on age. Among combined hormonal contraceptives, if no contraindication exists, natural estrogens should be preferred after 40 years old. On the other hand, progestin-only methods can also be safely used in the presence of cardiovascular risk factors. This review will address the main reasons why a woman may need an HC method and how to make a tailored and informed choice.

Given that menopause affects about half of the world's midlife population, it is crucial to understand its impact beyond traditional menopausal symptomology. For instance, many women, while transitioning through menopause, experience profound changes in body composition. These changes may contribute to postmenopausal reductions in metabolic health. This narrative review explores the influence of menopause on skeletal muscle and adipose tissue, highlighting the decline in muscle mass and strength and the gain and redistribution of adipose tissue, particularly the increase in visceral adiposity. Although menopausal changes in body composition are seemingly extensively studied, the longitudinal studies are not that common, and the precise mechanisms driving body composition changes remain unclear, with uncertainties surrounding the roles of hormonal shifts compared with regular aging, energy balance, and lifestyle factors. Notably, it remains debated whether menopause or estrogen meaningfully influences resting energy expenditure. The review also considers the potential mitigating effects of menopausal hormone therapy and regular exercise. Understanding these changes is essential for developing effective strategies to support women's health during and after menopause.

Menopausal symptoms, particularly vasomotor symptoms (VMS) and genitourinary syndrome of menopause (GSM), significantly affect women's quality of life (QoL). While menopausal hormone therapy (MHT) is the most effective treatment, contraindications such as estrogen-sensitive cancers and thromboembolic conditions limit its use for many women. This review explores alternative nonhormonal treatments, including pharmacological options like selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, gabapentin, clonidine, and neurokinin receptor antagonists (e.g., fezolinetant), alongside nonpharmacological approaches such as lifestyle modifications, cognitive-behavioral therapy, and acupuncture. These alternatives, though less effective than MHT, provide critical options for women unable to use hormonal therapies. Emerging treatments like fezolinetant demonstrate promise in reducing VMS by addressing the underlying pathophysiology, but safety concerns, such as hepatotoxicity, require ongoing monitoring. GSM management includes therapies such as vaginal estrogens, prasterone, and ospemifene, with tailored approaches necessary for cancer survivors. Emphasis is placed on individualized care, better patient education, and continued research into the safety and efficacy of these therapies to improve the QoL for postmenopausal women.

Young women diagnosed with endometrial cancer may have a fertility wish and may, under certain conditions, be offered fertility-sparing treatment. However, they may also have underlying infertility issues, as anovulation, obesity, polycystic ovary syndrome, and advanced maternal age are often found in women with endometrial cancer or atypical hyperplasia. These fertility issues may hinder pregnancy or prolong the time to pregnancy, in a situation where not much time is allowed to try for a pregnancy. Referral to a reproductive specialist is recommended as early as possible to detect any possible underlying infertility issues that might require assisted reproductive technology once a pregnancy is allowed or may even contradict fertility-sparing treatment. Ovarian reserve testing is a tool used to assess a woman's ovarian reserve, although it cannot, as such, be used to predict the chance of pregnancy. In case of obesity, weight loss is recommended as soon as possible.

With the rising incidence of endometrial cancer, including among young women, and the trend of increasing age among first-time mothers, the need for safe and effective fertility-sparing treatments for endometrial cancer and atypical endometrial hyperplasia has become crucial. Focusing on studies from the past decade, this review synthesizes findings on the safety and outcomes of fertility-sparing treatments for endometrial cancer and atypical endometrial hyperplasia and provides an overview of current treatment recommendations. Fertility-sparing treatment, including hysteroscopic tumor resection followed by hormonal therapy with oral progestins and/or the insertion of a levonorgestrel-releasing intrauterine device, can be offered to a selected group of women of reproductive age who wish to preserve their ability to become pregnant in the future. The safety of conservative treatment for women diagnosed with Stage 1A, Grade 1 endometrial cancer without myometrial invasion is high; however, current evidence on the safety of this treatment for women with Grade 1, Stage 2 endometrial cancer is limited. Even though the success rate in terms of pregnancies and deliveries is high, it is not as high as in the general population, and women should be informed of the potential need for assisted reproductive technology.