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Journal of the Formosan Medical... Jun 2024Few studies have compared the effects of tibolone versus hormone replacement therapy (HRT) on lower urinary tract symptoms and female sexual function. The current study... (Comparative Study)
Comparative Study
BACKGROUND
Few studies have compared the effects of tibolone versus hormone replacement therapy (HRT) on lower urinary tract symptoms and female sexual function. The current study aimed to compare these treatments.
METHODS
Women with climacteric symptoms were recruited consecutively and allocated to receive tibolone (2.5 mg) or estradiol valerate (1 mg) and medroxyprogesterone acetate (2.5 mg). Patients were followed up at 4 weeks and 12 weeks after treatment.
RESULTS
Overall, there were no significance of improvement in the International Prostate Symptoms Score (IPSS) scores in the HRT group. However, nocturia and the IPSS storage score improved after tibolone treatment. In addition, orgasm, satisfaction and pain improved after HRT. However, desire, lubrication, and Female Sexual Function Index (FSFI) total scores improved after tibolone treatment. There was a between-group difference in the change from baseline in the nocturia score after 4 weeks of treatment (0.1 ± 0.9 for HRT vs. -0.4 ± 1.2 for tibolone, p = 0.02). Nonetheless, there were no significant differences of the changes from baseline in the other IPSS and FSFI domains between the tibolone and HRT groups.
CONCLUSION
Despite the limited effect, tibolone seems to have more benefit in nocturia than HRT. In addition, tibolone seems to have benefits on overall low urinary tract storage symptoms; and both tibolone and HRT seem to have beneficial effects on female sexual function, despite there were no significant differences between tibolone and HRT.
Topics: Humans; Norpregnenes; Female; Middle Aged; Lower Urinary Tract Symptoms; Medroxyprogesterone Acetate; Estradiol; Estrogen Replacement Therapy; Adult; Nocturia; Treatment Outcome; Taiwan; Sexual Dysfunction, Physiological; Estrogen Receptor Modulators
PubMed: 38092655
DOI: 10.1016/j.jfma.2023.12.007 -
International Journal of Women's Health 2023To demonstrate the long-term outcome of a symptom-solving treatment model (SSTM).
Vagino-Laparoscopic Conservative Strategy of Hysterectomy in Indicated Cases of Severe Pelvic Endometriosis Followed by 24 Months of Depot-Medroxyprogesterone Acetate Therapy- A Symptom-Solving Treatment Model to Ease Surgical Challenges.
PURPOSE
To demonstrate the long-term outcome of a symptom-solving treatment model (SSTM).
PATIENTS AND METHODS
An observational study was carried out between June 2016 and December 2022 in our private setup on consecutive candidates of hysterectomy for severe pelvic endometriosis. Candidates were treated by the SSTM, which constitutes a systematic vagino-laparoscopic conservative strategy of hysterectomy with preservation of the ovary or ovaries followed by 24 months of postoperative depot-medroxyprogesterone acetate (DMPA) therapy. Cases were followed up to December 2022, 2.5 years beyond the last hysterectomy in May 2020.
MAIN OUTCOME MEASURES
Relief of endometriosis-associated symptoms and prevention of recurrence in the long term.
RESULTS
Symptomatic relief of endometriosis-related pain, such as cyclical dysmenorrhoea, pelvic pain, dyschezia, and vaginal pain, occurred in all 68 (100%) cases from the next expected date of menstruation. None of the cases showed a recurrence of endometriosis-related pelvic pain; overall, 37 (54.41%) cases crossed 4-6 years, and 31 (45.58%) cases crossed 2.5-4.0 years following the hysterectomy operation. Four (5.88%) cases had non-endometriotic pelvic pain. None of the cases required repeat surgery or had any major side effects or complications due to DMPA. No major perioperative complications were observed. The results were achieved without the requirement of challenging extensive retroperitoneal laparoscopic dissection, ureterolysis, and rectum surgeries.
CONCLUSION
This SSTM can be an option in indicated cases of severe pelvic endometriosis to provide symptom relief and prevent the recurrence of endometriosis-associated pelvic pain in the long term.
PubMed: 38077233
DOI: 10.2147/IJWH.S437362 -
Heliyon Dec 2023Canine Pyometra, also known as cystic endometrial hyperplasia complex, is a common reproductive issue in bitches. This study aimed to identify associated risk factors,...
Canine Pyometra, also known as cystic endometrial hyperplasia complex, is a common reproductive issue in bitches. This study aimed to identify associated risk factors, hematological variation, bacteria involved, and the most potent anti-bacterial against bacterial isolates of canine pyometra. Forty-five bitches of different habitats, breeds, and ages infected with pyometra were included in the study. The samples were cultured to isolate bacteria associated with the pyometra and antibiotic sensitivity was done for each bacterial isolates to get antibiogram. The study findings showed that potential risk factors such as age group, medroxyprogesterone acetate administration, and changes in the white blood cells parameters were significantly associated (P < 0.05) with the type of pyometra. Closed cervix pyometra in dogs showed significantly higher prevalence of clinical signs including depression, vomiting, abdominal enlargement, and fever compared to the open cervix pyometra. Low levels of red blood cells, pack cell volume, and hemoglobin indicated that the pyometra-infected dogs were more likely to have normocytic, normochromic, and non-regenerative anemia. Pyometra was attributed to an increase in AST (Aspertate aminotransferase), ALT (Alanine transaminase), ALP (Alkaline phosphatase), BUN (Blood Urea Nitrogen), and Creatinine while a decrease in serum albumin. Of the all bacterial isolates, (35.55%) was the most common pathogen isolated from canine pyometra, followed by spp. (26.66%). and spp. were susceptible to Imipenem, Amikacin, and Gentamicin while highly resistant to Ampicillin and Erythromycin. Imipenem, Amikacin, and Gentamicin were the most sensitive antibiotics, while Ampicillin and Erythromycin were the most resistant antibiotics for the bacterial strain isolated from canine pyometra. Multidrug resistant was observed in 26 of the isolated bacteria, indicating acquired resistance due to improper and uncontrolled use. Hence early diagnosis and close monitoring of antimicrobial susceptibility before therapeutic intervention is indispensable in preventing the global threat of antimicrobial resistance.
PubMed: 38076069
DOI: 10.1016/j.heliyon.2023.e22368 -
The Journal of Steroid Biochemistry and... Mar 2024Progestins used in hormonal contraceptives and menopausal hormone therapy (MHT) have been linked to increased breast cancer risk. Whether the association holds for all...
Progestins used in hormonal contraceptives and menopausal hormone therapy (MHT) have been linked to increased breast cancer risk. Whether the association holds for all progestins is unclear and the underlying mechanisms remain poorly understood. We directly compared the effects of four progestins (medroxyprogesterone acetate (MPA), norethisterone acetate (NET-A), levonorgestrel (LNG) and drospirenone (DRSP)) to each other and the natural progestogen progesterone (P) on selected cancer hallmarks. To provide mechanistic insight into these effects, we assessed the role of the progesterone receptor (PR), and the extracellular signal-related kinase (ERK1/2) and c-Jun N terminal (JNK) signaling pathways. We showed that the increased proliferation of the luminal T47D breast cancer cell line by P and all progestins, albeit to different extents, was inhibited by PR knockdown and inhibition of both the ERK1/2 and JNK pathways. While knockdown of the PR also blocked the upregulation of MKI67 and CCND1 mRNA expression by selected progestogens, only a role for the ERK1/2 pathway could be established in these effects. Similarly, only a role for the ERK1/2 pathway could be confirmed for progestogen-induced colony formation, whereas both the ERK1/2 and JNK pathways were required for cell migration in response to the three older progestins implicated in the etiology of breast cancer, MPA, NET-A and LNG. Together our results show that all the progestins elicit their effects on cell proliferation via a mechanism requiring the PR, ERK1/2 and JNK pathways. While the ERK1/2 and JNK pathways are also required for increased cell migration by the older progestins, only a role for the ERK1/2 pathway could be established in their effects on colony formation. Notably, the cytoplasmic PR was not needed for activation of the ERK1/2 pathway by the progestogens. Given that DRSP showed significantly lower proliferation than MPA and NET-A, and that it had no effect on breast cancer cell migration and colony formation, hormonal formulations containing the newer generation progestin DRSP may provide a better benefit/risk profile towards breast cancer than those containing the older generation progestins.
Topics: Humans; Female; Progestins; Breast Neoplasms; MAP Kinase Signaling System; Progesterone; Medroxyprogesterone Acetate; Levonorgestrel; Receptors, Progesterone; Receptors, Estrogen
PubMed: 38048919
DOI: 10.1016/j.jsbmb.2023.106440 -
Journal of Human Reproductive Sciences 2023Poor responders may benefit from recruiting a 'second wave' of antral follicles within the same cycle. This concept forms the basis of double stimulation which has been...
BACKGROUND
Poor responders may benefit from recruiting a 'second wave' of antral follicles within the same cycle. This concept forms the basis of double stimulation which has been named as 'DuoStim'. This protocol involves ovarian stimulation in both follicular and luteal phases with egg retrieval in each phase, respectively, to increase the number of oocytes and embryos in one menstrual cycle. This can be considered a potentially valuable option for women with poor ovarian reserve/response to maximise the number of oocytes retrieved in a single ovarian cycle in the shortest possible time.
AIMS
The aim of this study was to evaluate the efficacy of the DuoStim protocol in women classified as POSEIDON poor responders undergoing fertilization by comparing the embryological outcomes between the follicular and luteal phase stimulations in the same menstrual cycle.
SETTINGS AND DESIGN
This was a retrospective cohort study of 131 patients who enrolled to undergo DuoStim cycles from January 2021 to Sept. 2022, at a IVF center in a tertiary care hospital.
MATERIALS AND METHODS
The follicular phase stimulation used a standard antagonist protocol for the first oocyte retrieval. Thereafter, the luteal phase stimulation was started 3 days after the first retrieval, with the same dose of gonadotropin along with a daily 10 mg medroxyprogesterone acetate tablet, followed by a second oocyte retrieval. Blastocysts produced in both the phases were subsequently vitrified.
STATISTICAL ANALYSIS USED
The paired -test was used for comparing means and 95% confidence intervals (CIs) for different parameters. McNemar's test was used to compare paired proportions. The analysis was conducted using R statistical environment 4.2.
RESULTS
The mean number of oocytes retrieved and the mean number of utilizable blastocysts frozen per stimulation cycle were found to be significantly higher in the luteal phase as compared to the follicular phase (5.71 ± 3.95 vs. 4.87 ± 2.79, = 0.02, and 1.43 ± 1.22 vs. 0.95 ± 1, = 0.001, respectively). However, the mean fertilization rate and the mean blastocyst utilization rate were found to be similar between both the phases. The length of stimulation was found to be approximately 3 days longer in the luteal phase (12.63 ± 2.43 vs. 9.75 ± 1.85, = 0.001). Overall, the odds of obtaining a usable blastocyst in the luteal phase was found to be significantly higher than in the paired follicular phase (73.9% vs. 57.7%, = 0.012, odds ratio: 2.286 [95% CI: 1.186-4.636]). Also importantly, the luteal phase stimulation was able to rescue 68% (32/47) of patients where no blastocysts were formed in the follicular phase.
CONCLUSION
Our data demonstrate that in women with poor reserve, the addition of luteal stimulation could increase the chances of achieving a pregnancy by significantly increasing the number of eggs and transferable embryos per menstrual cycle compared to follicular stimulation alone. Furthermore, luteal phase stimulation in the same cycle proved to be an effective strategy to rescue POSEIDON poor responders with no embryos after the first stimulation.
PubMed: 38045502
DOI: 10.4103/jhrs.jhrs_76_23 -
PLOS Global Public Health 2023Since the introduction of subcutaneous depot medroxyprogesterone acetate (DMPA-SC) in 2018, Malawi has achieved national coverage of trained providers in the public...
Since the introduction of subcutaneous depot medroxyprogesterone acetate (DMPA-SC) in 2018, Malawi has achieved national coverage of trained providers in the public sector and steady increases in uptake of DMPA-SC. However, the rate of clients opting to self-inject DMPA-SC has remained lower than early acceptability studies suggested. Providers play an instrumental role in building client confidence to self-inject through counselling/training. This cross-sectional qualitative study explored the perspectives of providers and injectable clients on the integration of self-injection into contraceptive counselling, to identify best practices and potential gaps. The study was conducted at public sector sites in three districts (Nkhotakota, Mzimba South, Zomba) in Malawi. In-depth interviews were conducted with provider-administered injectable clients, self-injecting clients, and DMPA-SC trained providers. All providers interviewed reported successfully integrating self-injection into their approach. During group health education sessions, some providers reported focusing on benefits of self-injection to spark interest in the method, and then follow that up with more in-depth information during individual counselling. Due to time pressures, a minority of providers reported replacing individual counselling with small-group counselling and limited use of elements such as visualizations and demonstrations. Most providers skipped client practice on inanimate objects, feeling this was either not necessary or inappropriate given stock constraints. Self-injection clients tended to credit their decision to take up SI to receiving lengthy, comprehensive counselling/training, often inclusive of reassuring messages, visualizations, demonstrations and sometimes repeated trainings over time. Provider-administered clients tended to credit their lack of uptake of self-injection to fear and lack of confidence, often blaming themselves instead of the quality of their counselling/training-even while many felt their counselling/training had been rushed or incomplete. Providers should be supported to overcome time- and resource-pressures to invest in counselling/training best practices, to ensure sufficient support is provided to clients interested in self-injection.
PubMed: 38032864
DOI: 10.1371/journal.pgph.0002057 -
Frontiers in Endocrinology 2023The delayed-start gonadotropin-releasing hormone antagonist protocol seems effective for patients who are poor ovarian responders, but there are insufficient data on...
Original delayed-start ovarian stimulation protocol with a gonadotropin-releasing hormone antagonist, medroxyprogesterone acetate, and high-dose gonadotropin for poor responders and patients with poor-quality embryos.
INTRODUCTION
The delayed-start gonadotropin-releasing hormone antagonist protocol seems effective for patients who are poor ovarian responders, but there are insufficient data on whether it is also effective for patients with poor-quality embryos and low rates of good blastocyst formation. Specifically, the effectiveness of delayed-start gonadotropin-releasing hormone antagonists with progesterone has not been adequately investigated. Therefore, we compared the efficacy of the original delayed-start gonadotropin-releasing hormone antagonist protocol using medroxyprogesterone acetate (MPA) and high-dose gonadotropin in patients with poor ovarian response.
METHODS
Overall, 156 patients with recurrent assisted reproductive technology failure who underwent the original protocol were included. They received cetrorelix acetate (3 mg) and MPA (10 mg) on cycle day 3, and high-dose gonadotropin was initiated on day 11. When the leading follicle reached 14 mm, ganirelix acetate (0.25 mg) was administered until the trigger day. The number of oocytes retrieved, metaphase II (MII) oocytes, two pronuclear (2PN) zygotes, and good blastocysts and live birth rates were compared between the previous (Cycle A) and original (Cycle B) cycles in three groups (Group A, all patients; Group B, poor responders; and Group C, patients with poor-quality embryos).
RESULTS
In Group A (n=156), the number of MII oocytes (3.6 ± 3.3 versus 4.5 ± 3.6), 2PN zygotes (2.8 ± 2.9 versus 3.8 ± 3.1), good blastocysts (0.5 ± 0.9 versus 1.2 ± 1.6), and live birth rates (0.6 versus 24.4) significantly increased in Cycle B. Similar results were obtained in Group B (n=83; 2PN zygotes [1.7 ± 1.7 versus 2.3 ± 1.8], good blastocysts [0.4 ± 0.7 versus 0.9 ± 1.3], live birth rates [0 versus 18.1]) and Group C (n=73; MII oocytes [5.1 ± 3.8 versus 6.6 ± 4.0], 2PN zygotes [4.0 ± 3.4 versus 5.4 ± 3.4], good blastocysts [0.7 ± 1.1 versus 1.6 ± 1.9], and live birth rates [1.4 versus 31.5]).
CONCLUSION
This original protocol increased the number of MII oocytes retrieved, 2PN zygotes, good blastocysts, and live birth rates in both poor responders and in patients with poor-quality embryos.
Topics: Pregnancy; Female; Humans; Medroxyprogesterone Acetate; Pregnancy Rate; Gonadotropins; Gonadotropin-Releasing Hormone; Ovulation Induction; Hormone Antagonists
PubMed: 38027155
DOI: 10.3389/fendo.2023.1277873 -
Cancer Reports (Hoboken, N.J.) Jan 2024Progesterone therapy is a relatively inexpensive treatment option for endometrial and breast cancers, with few side effects. Two signaling pathways usually mediate the...
BACKGROUND
Progesterone therapy is a relatively inexpensive treatment option for endometrial and breast cancers, with few side effects. Two signaling pathways usually mediate the physiological effects of progesterone, namely genomic and non-genomic actions. Genomic action occurs slowly via the nuclear progesterone receptor (PR), whereas the membrane progesterone receptor (mPR) induces rapid non-genomic action.
AIMS
We investigated the effects of progesterone and various PR agonists on ovarian cancer cells.
METHODS AND RESULTS
PR expression of six serous ovarian cancer cell lines was examined by western blotting, and mPR expression was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). PR-negative and mPR-positive ovarian cancer cells were exposed to progesterone and seven types of PR agonists (medroxyprogesterone acetate [MPA], dehydroepiandrosterone, dienogest, levonorgestrel, drospirenone, pregnenolone, and allopregnanolone) at 10-400 μM, and viable cell counts after exposure for 30 min were measured using the water-soluble tetrazolium (WST-1) assay. Ovarian cancer cell lines were exposed to 100 μM progesterone, and the expression of BAX, a pro-apoptotic protein, after 1-5 min was examined by western blotting. Western blotting detected no PR expression in the six serous ovarian cancer cell lines. In contrast, RT-qPCR detected mPR expression in all six serous ovarian cancer cell lines. Progesterone and MPA-induced cell death in all tested ovarian cancer cell lines in a concentration-dependent manner, whereas no effect was observed for other PR agonists. Western blotting revealed that pro-apoptotic protein BAX expression occurred 1 min after exposure to progesterone, suggesting that the cytocidal effects are mediated by rapid non-genomic action.
CONCLUSION
Progesterone and MPA exhibited a rapid cytocidal effect on PR-negative ovarian cancer cells through non-genomic action. Progesterone and MPA could be novel adjuvant therapies for ovarian cancer.
Topics: Female; Humans; Progesterone; Receptors, Progesterone; bcl-2-Associated X Protein; Progestins; Medroxyprogesterone Acetate; Ovarian Neoplasms; Genomics; Cell Death
PubMed: 38013666
DOI: 10.1002/cnr2.1934 -
Journal of Pediatric and Adolescent... Apr 2024To explore the role of progestins as potential contributing factors for the development of hepatocellular adenoma (HA) METHODS: We describe 3 cases of adolescents and... (Review)
Review
STUDY OBJECTIVE
To explore the role of progestins as potential contributing factors for the development of hepatocellular adenoma (HA) METHODS: We describe 3 cases of adolescents and young adults who developed HA while on norethindrone (NET), as well as their management. In addition, we provide a comprehensive literature review on the association between progestins and HA.
RESULTS
Since 1983, 16 cases of HA in patients on progestins have been reported. Ten patients were on NET and 5 on a prodrug of NET (4 on norethindrone acetate [NETA] and 1 on lynestrenol). One individual had a norgestrel implant. Eight subsequently ceased all hormones: 4 experienced a size reduction, and 3 had complete resolution of their HA. Among our patients, 1 ceased NET and instead had a levonorgestrel intrauterine device inserted, and another swapped from NET to oral medroxyprogesterone acetate. Both experienced complete resolution of their HA. The third ceased NET and underwent a hysterectomy, with size reduction of her HA.
CONCLUSION
These cases and the literature review suggest an association between progestin exposure, in particular NET and its prodrugs, and the development of HA. The pathophysiology is unknown but may include peripheral conversion of NET and NETA to ethinyl estradiol or a specific action of 19-nortestosterone derivatives on hepatocytes, especially those with higher systemic doses compared with the levonorgestrel intrauterine device. There are no case reports relating to other forms of progestins, such as 17-hydroxyprogesterone, which may be important when considering alternative therapeutic options in females requiring effective menstrual management who have comorbidities.
Topics: Adolescent; Female; Humans; Adenoma, Liver Cell; Carcinoma, Hepatocellular; Levonorgestrel; Liver Neoplasms; Norethindrone; Progestins
PubMed: 37977437
DOI: 10.1016/j.jpag.2023.11.003