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Human Reproduction Update May 2024The establishment and maintenance of pregnancy depend on endometrial competence. Asherman syndrome (AS) and intrauterine adhesions (IUA), or endometrial atrophy (EA) and...
BACKGROUND
The establishment and maintenance of pregnancy depend on endometrial competence. Asherman syndrome (AS) and intrauterine adhesions (IUA), or endometrial atrophy (EA) and thin endometrium (TE), can either originate autonomously or arise as a result from conditions (i.e. endometritis or congenital hypoplasia), or medical interventions (e.g. surgeries, hormonal therapies, uterine curettage or radiotherapy). Affected patients may present an altered or inadequate endometrial lining that hinders embryo implantation and increases the risk of poor pregnancy outcomes and miscarriage. In humans, AS/IUA and EA/TE are mainly treated with surgeries or pharmacotherapy, however the reported efficacy of these therapeutic approaches remains unclear. Thus, novel regenerative techniques utilizing stem cells, growth factors, or tissue engineering have emerged to improve reproductive outcomes.
OBJECTIVE AND RATIONALE
This review comprehensively summarizes the methodologies and outcomes of emerging biotechnologies (cellular, acellular, and bioengineering approaches) to treat human endometrial pathologies. Regenerative therapies derived from human tissues or blood which were studied in preclinical models (in vitro and in vivo) and clinical trials are discussed.
SEARCH METHODS
A systematic search of full-text articles available in PubMed and Embase was conducted to identify original peer-reviewed studies published in English between January 2000 and September 2023. The search terms included: human, uterus, endometrium, Asherman syndrome, intrauterine adhesions, endometrial atrophy, thin endometrium, endometritis, congenital hypoplasia, curettage, radiotherapy, regenerative therapy, bioengineering, stem cells, vesicles, platelet-rich plasma, biomaterials, microfluidic, bioprinting, organoids, hydrogel, scaffold, sheet, miRNA, sildenafil, nitroglycerine, aspirin, growth hormone, progesterone, and estrogen. Preclinical and clinical studies on cellular, acellular, and bioengineering strategies to repair or regenerate the human endometrium were included. Additional studies were identified through manual searches.
OUTCOMES
From a total of 4366 records identified, 164 studies (3.8%) were included for systematic review. Due to heterogeneity in the study design and measured outcome parameters in both preclinical and clinical studies, the findings were evaluated qualitatively and quantitatively without meta-analysis. Groups using stem cell-based treatments for endometrial pathologies commonly employed mesenchymal stem cells (MSCs) derived from the human bone marrow or umbilical cord. Alternatively, acellular therapies based on platelet-rich plasma (PRP) or extracellular vesicles are gaining popularity. These are accompanied by the emergence of bioengineering strategies based on extracellular matrix (ECM)-derived hydrogels or synthetic biosimilars that sustain local delivery of cells and growth factors, reporting promising results. Combined therapies that target multiple aspects of tissue repair and regeneration remain in preclinical testing but have shown translational value. This review highlights the myriad of therapeutic material sources, administration methods, and carriers that have been tested.
WIDER IMPLICATIONS
Therapies that promote endometrial proliferation, vascular development, and tissue repair may help restore endometrial function and, ultimately, fertility. Based on the existing evidence, cost, accessibility, and availability of the therapies, we propose the development of triple-hit regenerative strategies, potentially combining high-yield MSCs (e.g. from bone marrow or umbilical cord) with acellular treatments (PRP), possibly integrated in ECM hydrogels. Advances in biotechnologies together with insights from preclinical models will pave the way for developing personalized treatment regimens for patients with infertility-causing endometrial disorders such as AS/IUA, EA/TE, and endometritis.
REGISTRATION NUMBER
https://osf.io/th8yf/.
PubMed: 38796750
DOI: 10.1093/humupd/dmae013 -
Archives of Gynecology and Obstetrics Jan 2024The immune system is influenced by many factors, including female sex hormones. The extent of this influence, however, is not completely understood so far. This... (Review)
Review
PURPOSE
The immune system is influenced by many factors, including female sex hormones. The extent of this influence, however, is not completely understood so far. This systematic literature review aims at giving an overview of the existing concepts on how endogenous progesterone influences the female immune system along the menstrual cycle.
METHODS
The inclusion criteria were healthy female subjects in their reproductive age with a regular menstrual cycle. The exclusion criteria were exogenous progesterone, animal models, nonhealthy study populations and pregnancy. This led to 18 papers covered in this review. The search was performed using the databases EMBASE, Ovid MEDLINE and Epub, and the last search was conducted on September 18, 2020. Our findings were analyzed in four categories: cellular immune defense, humoral immune defense, objective and subjective clinical parameters.
RESULTS
We demonstrated that progesterone acts in an immunosuppressive way, favoring a Th-2-like cytokine profile. Further, we showed that progesterone inhibits mast cell degranulation and relaxes smooth muscle cells. Furthermore, we found supporting evidence for a so-called window of vulnerability after ovulation, where immune functions are lowered and mediated through progesterone.
CONCLUSION
The clinical relevance of these findings is not completely understood yet. As the sample sizes of included studies were rather small and the content of them was broad, further investigations are needed to define to which extent the described changes actually clinically meaningful, whether they are capable of influencing the female health and how these findings can be used to increase well-being.
Topics: Female; Humans; Immune System; Menstrual Cycle; Ovulation; Progesterone; Reproduction
PubMed: 36933040
DOI: 10.1007/s00404-023-06996-9 -
Journal of Obstetrics and Gynaecology :... Dec 2024The number of patients desiring fertility-preserving treatment for endometrial cancer rather than standard surgical management continues to increase. (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The number of patients desiring fertility-preserving treatment for endometrial cancer rather than standard surgical management continues to increase.
OBJECTIVE
We aimed to evaluate the efficacies of fertility-preserving treatments on the live birth rate, remission and relapse rates for women with stage 1a grade 1 endometrial carcinoma to support patient counselling.
METHODS
We performed a meta-analysis for our primary outcomes of overall remission and relapse rate, and for secondary analysis, we divided papers into treatment type: systemic progestins, intrauterine progestins or hysteroscopic resection and adjuvant hormonal treatment.
RESULTS
Thirty-five observational studies met inclusion criteria, with a total of 624 patients. Overall, conservative treatment of endometrial cancer showed a remission rate of 77% (95% CI: 70-84%), a relapse rate of 20% (95% CI: 13-27%) and a live birth rate of 20% (95% CI: 15-25%) with more favourable outcomes for the hysteroscopic resection group.
CONCLUSIONS
Hysteroscopic resection and adjuvant hormonal treatment had the most favourable fertility and oncological outcomes. Further high-quality prospective multi-centre trials are warranted to determine the optimal treatment regimen and dosage and risk stratification for these patients.
Topics: Humans; Female; Progestins; Prospective Studies; Fertility Preservation; Antineoplastic Agents, Hormonal; Neoplasm Recurrence, Local; Endometrial Neoplasms; Fertility; Recurrence; Endometrial Hyperplasia
PubMed: 38126736
DOI: 10.1080/01443615.2023.2294329 -
Human Reproduction (Oxford, England) Jul 2023Does a personalized embryo transfer (pET) guided by tests for endometrial receptivity (TER) increase the effectiveness of ART procedures? (Meta-Analysis)
Meta-Analysis
STUDY QUESTION
Does a personalized embryo transfer (pET) guided by tests for endometrial receptivity (TER) increase the effectiveness of ART procedures?
SUMMARY ANSWER
The use of TER-guided pET is not supported by current published evidence in women without repeated implantation failure (RIF), while in women with RIF more research is needed to assess a potential benefit.
WHAT IS KNOWN ALREADY
Implantation rates are still far from ideal, especially in some patients that have RIF with good-quality embryos. As a potential solution, a wide range of diverse TER use different sets of genes to identify displacements of the window of implantation to adjust the individual length of progesterone exposure in a pET.
STUDY DESIGN, SIZE, DURATION
A systematic review with meta-analysis was performed. Search terms included endometrial receptivity analysis, ERA, personalized embryo transfer. CENTRAL, PubMed, Embase, reference lists, clinical trials registers, and conference proceedings (search date October 2022) were searched, with no language restrictions.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Randomized controlled trials (RCTs) and cohort studies comparing a pET guided by TER vs standard embryo transfer (sET) in different subgroups that undergo ART were identified. We also investigated pET in non-receptive-TER vs sET in receptive-TER, and pET in a specific population vs sET in a general population. Risk of bias (RoB) was assessed with the Cochrane tool and ROBINS-I. Only those with low/moderate RoB underwent meta-analysis. The GRADE approach was used to evaluate the certainty of evidence (CoE).
MAIN RESULTS AND THE ROLE OF CHANCE
We screened 2136 studies and included 35 (85% used ERA and 15% used other TER). Two studies were RCTs comparing endometrial receptivity analysis (ERA)-guided pET vs sET in women with no history of RIF. In women without RIF, no important differences (moderate-CoE) were found in live birth rates and clinical pregnancy rates (CPR). We also performed a meta-analysis of four cohort studies that were adjusted for confounding. In agreement with the RCTs, no benefits were found in women without RIF. However, in women with RIF, low CoE suggests that pET might improve the CPR (OR 2.50, 95% CI 1.42-4.40).
LIMITATIONS, REASONS FOR CAUTION
We found few studies with low RoB. Only two RCTs in women without RIF were published, and none in women with RIF. Furthermore, the heterogeneity observed in populations, interventions, co-interventions, outcomes, comparisons, and procedures limited the pooling of many of the included studies.
WIDER IMPLICATIONS OF THE FINDINGS
In the population of women without RIF, in agreement with previously published reviews, pET did not prove to be more effective than sET and, therefore, it precludes the routine use of this strategy in this population until more evidence is available. However, more research is advisable in women with RIF as low-certainty evidence from observational studies adjusted for confounders suggests that the CPR might be higher with pET guided by TER in this population. Although this review presents the best available evidence, it is still insufficient to change current policies.
STUDY FUNDING/COMPETING INTEREST(S)
No specific funding was obtained for this study. There are no conflicts of interest to declare.
REGISTRATION NUMBER
PROSPERO CRD42022299827.
Topics: Pregnancy; Female; Humans; Pregnancy Rate; Embryo Transfer; Embryo Implantation; Endometrium; Progesterone; Live Birth
PubMed: 37203432
DOI: 10.1093/humrep/dead098 -
BJOG : An International Journal of... Jun 2024There is no consensus on tests required to either diagnose unexplained infertility or use for research inclusion criteria. This leads to heterogeneity and bias affecting...
BACKGROUND
There is no consensus on tests required to either diagnose unexplained infertility or use for research inclusion criteria. This leads to heterogeneity and bias affecting meta-analysis and best practice advice.
OBJECTIVES
This systematic review analyses the variability of inclusion criteria applied to couples with unexplained infertility. We propose standardised criteria for use both in future research studies and clinical diagnosis.
SEARCH STRATEGY
CINAHL and MEDLINE online databases were searched up to November 2022 for all published studies recruiting couples with unexplained infertility, available in full text in the English language.
DATA COLLECTION AND ANALYSIS
Data were collected in an Excel spreadsheet. Results were analysed per category and methodology or reference range.
MAIN RESULTS
Of 375 relevant studies, only 258 defined their inclusion criteria. The most commonly applied inclusion criteria were semen analysis, tubal patency and assessment of ovulation in 220 (85%), 232 (90%), 205 (79.5%) respectively. Only 87/220 (39.5%) studies reporting semen analysis used the World Health Organization (WHO) limits. Tubal patency was accepted if bilateral in 145/232 (62.5%) and if unilateral in 24/232 (10.3%). Ovulation was assessed using mid-luteal serum progesterone in 115/205 (56.1%) and by a history of regular cycles in 87/205 (42.4%). Other criteria, including uterine cavity assessment and hormone profile, were applied in less than 50% of included studies.
CONCLUSIONS
This review highlights the heterogeneity among studied populations with unexplained infertility. Development and application of internationally accepted criteria will improve the quality of research and future clinical care.
Topics: Female; Humans; Male; Infertility; Infertility, Female; Ovulation Detection; Semen Analysis
PubMed: 37957032
DOI: 10.1111/1471-0528.17697 -
The Journal of Maternal-fetal &... Dec 2023There is ongoing interest in glucocorticoid treatment during oocyte stimulation to treat infertility in women who have undergone Assisted Reproductive Technology (ART). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is ongoing interest in glucocorticoid treatment during oocyte stimulation to treat infertility in women who have undergone Assisted Reproductive Technology (ART).
OBJECTIVE
This meta-analysis was performed to evaluate the efficiency and safety of adjuvant glucocorticoid therapy on pregnancy outcomes in infertile women undergoing ART cycles.
STUDY DESIGN
A literature search was performed in PubMed, EMBASE, Web of Science, and the Cochrane Library up to December 2022. To assess the efficacy and safety of additional glucocorticoid treatment during ovulation induction in women who underwent IVF or ICSI treatment, only randomized controlled trials were included.
RESULTS
Overall, glucocorticoid therapy during ovulation showed a nonsignificant effect of prednisolone improving the live birth rate (OR = 1.03, 95% CI [.75, 1.43], I = .0%, = .84), abortion rate (OR = 1.14, 95% CI [.62, 2.08], I = 31%, = .68), and implantation rate (OR = 1.1, 95% CI [.82, 1.5], I = 8%, = .52) of infertile women compared to the control group. The present meta-analysis revealed that the clinical pregnancy rate per cycle tended to increase after glucocorticoid treatment (OR = 1.29, 95% CI [1.02, 1.63], I = 8%, = .52).
CONCLUSIONS
The present meta-analysis suggested that ovarian stimulation prednisolone therapy does not significantly improve clinical outcomes in women undergoing IVF/ICSI. Although the results indicated that adjuvant glucocorticoid therapy during ovarian stimulation may increase the clinical pregnancy rate, subgroup analysis showed that it was affected by infertility factors, dose schedules, and length of treatment. Therefore, these results should be interpreted with caution.
Topics: Female; Pregnancy; Humans; Glucocorticoids; Infertility, Female; Ovulation Induction; Prednisolone; Adjuvants, Pharmaceutic; Dietary Supplements
PubMed: 37385781
DOI: 10.1080/14767058.2023.2227310 -
NPJ Microgravity Jan 2024With increasing possibilities of multi-year missions in deep space, colonizing other planets, and space tourism, it is important to investigate the effects of space... (Review)
Review
With increasing possibilities of multi-year missions in deep space, colonizing other planets, and space tourism, it is important to investigate the effects of space travel on human reproduction. This study aimed to systematically review and summarize the results of available literature on space travel, microgravity, and space radiation, or Earth-based spaceflight analogues impact on female and male reproductive functions in humans. This systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and Space Biomedicine Systematic Review methods. The search was performed using three databases: PubMed, Web of Science, and Medline Complete. During the database search, 364 studies were identified. After the study selection process, 16 studies were included in the review. Five studies included female participants, and the findings show an increased risk of thromboembolism in combined oral contraceptive users, decreased decidualization, functional insufficiency of corpus luteum, and decreased progesterone and LH levels related to space travel or its simulation. Male participants were included in 13 studies. In males, reproductive health considerations focused on the decrease in testosterone and sex hormone-binding globulin levels, the ratio of male offspring, sperm motility, sperm vitality, and the increase in sperm DNA fragmentation related to space travel or its simulation. Results of this systematic review highlight the need to focus more on the astronaut's reproductive health in future research, as only 16 studies were found during the literature search, and many more research questions related to reproductive health in astronauts still need to be answered.
PubMed: 38238348
DOI: 10.1038/s41526-024-00351-1 -
The Cochrane Database of Systematic... Nov 2023Currently, gonadotrophin releasing hormone (GnRH) analogues are used to prevent premature ovulation in ART cycles. However, their costs remain high, the route of... (Review)
Review
Progestogens for prevention of luteinising hormone (LH) surge in women undergoing controlled ovarian hyperstimulation as part of an assisted reproductive technology (ART) cycle.
BACKGROUND
Currently, gonadotrophin releasing hormone (GnRH) analogues are used to prevent premature ovulation in ART cycles. However, their costs remain high, the route of administration is invasive and has some adverse effects. Oral progestogens could be cheaper and effective to prevent a premature LH surge.
OBJECTIVES
To evaluate the effectiveness and safety of using progestogens to avoid spontaneous ovulation in women undergoing controlled ovarian hyperstimulation (COH).
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility Group trials register, CENTRAL, MEDLINE, Embase and PsycINFO in Dec 2021. We contacted study authors and experts to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that included progestogens for ovulation inhibition in women undergoing controlled ovarian hyperstimulation (COH).
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures recommended by Cochrane, including the risk of bias (RoB) assessment. The primary review outcomes were live birth rate (LBR) and oocyte pick-up cancellation rate (OPCR). Secondary outcomes were clinical pregnancy rate (CPR), cumulative pregnancy, miscarriage rate (MR), multiple pregnancies, LH surge, total and MII oocytes, days of stimulation, dose of gonadotropins, and moderate/severe ovarian hyperstimulation syndrome (OHSS) rate. The primary analyses were restricted to studies at overall low and some concerns RoB, and sensitivity analysis included all studies. We used the GRADE approach to assess the certainty of evidence.
MAIN RESULTS
We included 14 RCTs (2643 subfertile women undergoing ART, 47 women used oocyte freezing for fertility preservation and 534 oocyte donors). Progestogens versus GnRH antagonists We are very uncertain of the effect of medroxyprogesterone acetate (MPA) 10 mg compared with cetrorelix on the LBR in poor responders (odds ratio (OR) 1.25, 95% confidence interval (CI) 0.73 to 2.13, one RCT, N = 340, very-low-certainty evidence), suggesting that if the chance of live birth following GnRH antagonists is assumed to be 18%, the chance following MPA would be 14% to 32%. There may be little or no difference in OPCR between progestogens and GnRH antagonists, but due to wide Cs (CIs), we are uncertain (OR 0.92, 95%CI 0.42 to 2.01, 3 RCTs, N = 648, I² = 0%, low-certainty evidence), changing the chance of OPCR from 4% with progestogens to 2% to 8%. Given the imprecision found, no conclusions can be retrieved on CPR and MR. Low-quality evidence suggested that using micronised progesterone in normo-responders may increase by 2 to 6 the MII oocytes in comparison to GnRH antagonists. There may be little or no differences in gonadotropin doses. Progestogens versus GnRH agonists Results were uncertain for all outcomes comparing progestogens with GnRH agonists. One progestogen versus another progestogen The analyses comparing one progestogen versus another progestogen for LBR did not meet our criteria for primary analyses. The OPCR was probably lower in the MPA 10 mg in comparison to MPA 4 mg (OR 2.27, 95%CI 0.90 to 5.74, one RCT, N = 300, moderate-certainty evidence), and MPA 4 mg may be lower than micronised progesterone 100 mg, but due to wide CI, we are uncertain of the effect (OR 0.81, 95%CI 0.43 to 1.53, one RCT, N = 300, low-certainty evidence), changing the chance of OPCR from 5% with MPA 4 mg to 5% to22%, and from 17% with micronised progesterone 100 mg to 8% to 24%. When comparing dydrogesterone 20 mg to MPA, the OPCR is probably lower in the dydrogesterone group in comparison to MPA 10 mg (OR 1.49, 95%CI 0.80 to 2.80, one RCT, N = 520, moderate-certainty evidence), and it may be lower in dydrogesterone group in comparison to MPA 4 mg but due to wide confidence interval, we are uncertain of the effect (OR 1.19, 95%CI 0.61 to 2.34, one RCT, N = 300, low-certainty evidence), changing the chance of OPCR from 7% with dydrogesterone 20 to 6-17%, and in MPA 4 mg from 12% to 8% to 24%. When comparing dydrogesterone 20 mg to micronised progesterone 100 mg, the OPCR is probably lower in the dydrogesterone group (OR 1.54, 95%CI 0.94 to 2.52, two RCTs, N=550, I² = 0%, moderate-certainty evidence), changing OPCR from 11% with dydrogesterone to 10% to 24%. We are very uncertain of the effect in normo-responders of micronised progesterone 100 mg compared with micronised progesterone 200 mg on the OPCR (OR 0.35, 95%CI 0.09 to 1.37, one RCT, N = 150, very-low-certainty evidence). There is probably little or no difference in CPR and MR between MPA 10 mg and dydrogesterone 20 mg. There may be little or no differences in MII oocytes and gonadotropins doses. No cases of moderate/severe OHSS were reported in most of the groups in any of the comparisons.
AUTHORS' CONCLUSIONS
Little or no differences in LBR may exist when comparing MPA 4 mg with GnRH agonists in normo-responders. OPCR may be slightly increased in the MPA 4 mg group, but MPA 4 mg reduces the doses of gonadotropins in comparison to GnRH agonists. Little or no differences in OPCR may exist between progestogens and GnRH antagonists in normo-responders and donors. However, micronised progesterone could improve by 2 to 6 MII oocytes. When comparing one progestogen to another, dydrogesterone suggested slightly lower OPCR than MPA and micronised progesterone, and MPA suggested slightly lower OPCR than the micronised progesterone 100 mg. Finally, MPA 10 mg suggests a lower OPCR than MPA 4 mg. There is uncertainty regarding the rest of the outcomes due to imprecision and no solid conclusions can be drawn.
Topics: Female; Humans; Pregnancy; Abortion, Spontaneous; Dydrogesterone; Gonadotropin-Releasing Hormone; Gonadotropins; Live Birth; Luteinizing Hormone; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy Rate; Progesterone; Progestins; Reproductive Techniques, Assisted
PubMed: 38032057
DOI: 10.1002/14651858.CD013827.pub2 -
European Journal of Neurology Sep 2023Hormonal replacement therapy (HRT) is used for symptomatic treatment of menopause. Some evidence suggests a proconvulsant effect of estrogen and an anticonvulsant role... (Review)
Review
BACKGROUND AND PURPOSE
Hormonal replacement therapy (HRT) is used for symptomatic treatment of menopause. Some evidence suggests a proconvulsant effect of estrogen and an anticonvulsant role of progesterone. Thus, the use of exogenous sex steroid hormones might influence the course of epilepsy in peri- and postmenopausal women with epilepsy (WWE). We conducted a systematic review on the impact of HRT on the frequency of seizures of WWE.
METHODS
PubMed and Scopus were searched for articles published from inception until August 2022. Abstracts from the past 5 years from the European Academy of Neurology and European Epilepsy Congresses were also reviewed. Article reference lists were screened, and relevant articles were retrieved for consultation. Interventional and observational studies on WWE and animal models of estrogen deficiency were included. Critical appraisal was performed using the revised Cochrane risk-of-bias tool for randomized trials and ROBINS-E tool.
RESULTS
Of 497 articles screened, 13 studies were included, including three human studies. One cross-sectional study showed a decrease in seizure frequency in WWE using combined HRT, a case-control study showed an increase in comparison with controls, and a randomized clinical trial found a dose-dependent increase in seizure frequency in women with focal epilepsy taking combined HRT. Ten studies addressing the impact of HRT in rat models were also included, which showed conflicting results.
CONCLUSIONS
There is scarce evidence of the impact of HRT in WWE. Further studies should evaluate the harmful potential, and prospective registries are needed for monitoring this population.
Topics: Female; Humans; Animals; Rats; Postmenopause; Case-Control Studies; Prospective Studies; Cross-Sectional Studies; Epilepsy; Seizures; Estrogens; Gonadal Steroid Hormones; Randomized Controlled Trials as Topic
PubMed: 37326003
DOI: 10.1111/ene.15916 -
Climacteric : the Journal of the... Apr 2024The genitourinary syndrome of menopause (GSM) affects up to 84% of postmenopausal women and may significantly reduce the quality of life in some. For symptom relief,...
The genitourinary syndrome of menopause (GSM) affects up to 84% of postmenopausal women and may significantly reduce the quality of life in some. For symptom relief, there are several non-hormonal and hormonal vaginal products available. In Europe, vaginal estriol (E3) is the most frequently chosen estrogen for GSM treatment. The aim of this systematic review was to assess the impact of vaginal E3 on serum sex hormone levels, an outcome that has been previously used to assess safety in similar products. In our review, we did not find any alterations in serum estrone, estradiol, testosterone, progesterone and sex hormone binding globulin levels after vaginal E3 application. In contrast, some studies showed a minimal and transient decrease in serum gonadotropin levels, which however remained within the postmenopausal range. Similarly, only a few studies reported a minimal and transient increase of serum E3 levels, with the rest reporting no changes. The lack of clinically relevant long-term changes in serum sex hormone levels supports the current literature providing evidence about the safety of vaginal E3 products.
Topics: Female; Humans; Estriol; Estrogens; Menopause; Quality of Life; Vagina
PubMed: 38164918
DOI: 10.1080/13697137.2023.2287624