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Contraception Apr 2024To evaluate ovulation risk among women enrolling in an emergency contraception (EC) study by measuring contraceptive steroids and ovarian hormones.
Use of serum evaluation of contraceptive and ovarian hormones to assess reduced risk of pregnancy among women presenting for emergency contraception in a multicenter clinical trial.
OBJECTIVES
To evaluate ovulation risk among women enrolling in an emergency contraception (EC) study by measuring contraceptive steroids and ovarian hormones.
STUDY DESIGN
We used standard chemiluminescent assays to evaluate endogenous hormones (estradiol, progesterone, follicle stimulating hormone, luteinizing hormone) and liquid chromatography-tandem triple quadrupole mass spectrometry to simultaneously analyze concentrations of ethinylestradiol, dienogest, norelgestromin (NGMN), norethindrone (NET), gestodene, levonorgestrel (LNG), etonogestrel (ENG), segesterone acetate, medroxyprogesterone acetate (MPA), and drospirenone in serum samples obtained at the time of enrollment in a recent study comparing oral ulipristal acetate and LNG EC in women with weight ≥80 kg reporting no recent use of hormonal contraception.
RESULTS
We enrolled 532 and obtained a valid baseline blood sample from 520 women. Of these, 117 (22.5%) had detectable concentrations of progestin (MPA [n = 58, 11.2%], LNG [50, 9.6%], ENG [11, 2.1%], NET [5, 0.96%], NGMN [3, 0.06%], or drospirenone [1, 0.02%]). LNG was co-detected in all three participants with samples containing NGMN. Multiple progestins were detected in eight other women: ENG/MPA (1), ENG/LNG (2), and MPA/LNG (5). Samples from 55 (10.6%) had concentrations of one or more progestin considered above the minimum level for contraceptive (MPA ≥ 0.1 ng/mL, n = 19; NGMN/LNG ≥ 0.2 ng/mL, n = 31; ENG ≥ 0.09 ng/mL, n = 8; NET ≥ 0.35 ng/mL, n = 4). We detected concentrations of serum progesterone ≥ 3 ng/mL, indicative of luteal phase (postovulation) status, in an additional 194 (37.3%) samples.
CONCLUSIONS
More than one-third of enrolled in our clinical trial of oral EC had evidence of prior ovulation at the time of enrollment. Additionally, about 23% had evidence of recent use of hormonal contraception. These results would have decreased the expected risk of pregnancy in the study.
IMPLICATIONS
Many participants in a recent clinical trial of oral emergency contraception did not appear to be at risk for pregnancy or would not have benefited from intervention due to cycle timing. Investigators should consider the effects of these findings on expected pregnancy rates when determining sample size in future EC clinical trials, particularly when using noninferiority designs or historical controls.
PubMed: 38670302
DOI: 10.1016/j.contraception.2024.110475 -
Steroids Jun 2024Depo-medroxyprogesterone acetate (DMPA) functions as a contraceptive method by inhibiting the secretion of gonadotropins, which prevents follicular maturation and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Depo-medroxyprogesterone acetate (DMPA) functions as a contraceptive method by inhibiting the secretion of gonadotropins, which prevents follicular maturation and ovulation, as well as thinning of the endometrium leading to unscheduled vaginal bleeding and subsequent discontinuation of DMPA. Our study aimed to evaluate the efficacy and safety of clomiphene citrate (CC) in stopping bleeding among DMPA users.
MATERIALS AND METHODS
We randomly assigned 200 DMPA users using a computer-generated random numbers table in a 1:1 ratio to one of two groups; the study group, which received CC at a dose of 50 mg twice daily for five days (n = 100), and the control group, which received a placebo for five days (n = 100). Our primary outcome measure was the onset and duration of bleeding cessation. Secondary outcomes included endometrial thickness, recurrence of vaginal bleeding, and any reported side effects associated with CC use.
RESULTS
Clomiphene citrate significantly resulted in early cessation of vaginal bleeding in 83 % of the patients, which continued for three months of follow-up. In addition, the recurrence of vaginal bleeding was significantly reduced in the CC group compared to the control group (11 % vs. 67 %; p < 0.001). Endometrial thickness was significantly greater in the CC group than in the control group (p < 0.001). Breast tenderness was more frequently reported in the study group, with no difference in dyspareunia between the two groups.
CONCLUSIONS
Clomiphene citrate is effective in controlling bleeding among DMPA users. Further studies are encouraged to confirm our findings.
Topics: Humans; Female; Clomiphene; Medroxyprogesterone Acetate; Adult; Uterine Hemorrhage; Young Adult
PubMed: 38636732
DOI: 10.1016/j.steroids.2024.109425 -
Scientific Reports Apr 2024Decidualization can be induced by culturing human endometrial stromal cells (ESCs) with several decidualization stimuli, such as cAMP, medroxyprogesterone acetate (MPA)...
Decidualization can be induced by culturing human endometrial stromal cells (ESCs) with several decidualization stimuli, such as cAMP, medroxyprogesterone acetate (MPA) or Estradiol (E). However, it has been unclear how decidualized cells induced by different stimuli are different. We compared transcriptomes and cellular functions of decidualized ESCs induced by different stimuli (MPA, E + MPA, cAMP, and cAMP + MPA). We also investigated which decidualization stimulus induces a closer in vivo decidualization. Differentially expressed genes (DEGs) and altered cellular functions by each decidualization stimuli were identified by RNA-sequence and gene-ontology analysis. DEGs was about two times higher for stimuli that use cAMP (cAMP and cAMP + MPA) than for stimuli that did not use cAMP (MPA and E + MPA). cAMP-using stimuli altered the cellular functions including angiogenesis, inflammation, immune system, and embryo implantation whereas MPA-using stimuli (MPA, E + MPA, and cAMP + MPA) altered the cellular functions associated with insulin signaling. A public single-cell RNA-sequence data of the human endometrium was utilized to analyze in vivo decidualization. The altered cellular functions by in vivo decidualization were close to those observed by cAMP + MPA-induced decidualization. In conclusion, decidualized cells induced by different stimuli have different transcriptome and cellular functions. cAMP + MPA may induce a decidualization most closely to in vivo decidualization.
Topics: Female; Humans; Cells, Cultured; Endometrium; Medroxyprogesterone Acetate; Stromal Cells; Gene Expression; RNA; Decidua
PubMed: 38565619
DOI: 10.1038/s41598-024-58065-z -
Annals of Allergy, Asthma & Immunology... Mar 2024Immediate IgE-mediated hypersensitivity reactions to polyethylene glycol (PEG) are rare. Our understanding of PEG hypersensitivity is limited.
BACKGROUND
Immediate IgE-mediated hypersensitivity reactions to polyethylene glycol (PEG) are rare. Our understanding of PEG hypersensitivity is limited.
OBJECTIVE
To evaluate the clinical characteristics and investigation outcomes of the largest cohort of patients with PEG allergy reported.
METHODS
A total of 44 patients investigated for suspected PEG allergy across 4 United Kingdom tertiary allergy centers between October 2013 and December 2020 were studied. Clinical characteristics, index reaction, and approaches to and outcomes of allergy investigations were analyzed.
RESULTS
PEG hypersensitivity was confirmed in 42 of 44 cases. Macrogol laxatives were the most common index drugs reported (23%), followed by depo-medroxyprogesterone (19%), oral penicillin V (10%), and depo-methylprednisolone (10%). In general, 61% experienced grade III anaphylaxis. Intradermal testing (IDT) increased the diagnostic sensitivity from 51% to 85%. Five patients experienced systemic reactions during IDT. Of the 5 patients, 2 were skin prick test positive to a high molecular weight PEG. Three patients with negative skin test results had positive drug provocation test results. Seven patients with PEG allergy reported tolerance to H-antihistamines containing PEG. Administration of messenger RNA COVID-19 or Oxford/AstraZeneca COVID-19 vaccines was tolerated in all 16 patients to whom they were administered.
CONCLUSION
PEG hypersensitivity is an uncommon cause of drug-induced anaphylaxis. Four index drugs accounted for two-thirds of the cases, and reactions to these drugs should prompt PEG hypersensitivity investigations. PEG IDT increases diagnostic yield. The role of skin prick test with higher molecular weight PEGs requires further attention. Further studies are required to understand PEG thresholds and PEG equivalent doses of various administration routes. COVID-19 vaccines were tolerated by all exposed.
PubMed: 38561050
DOI: 10.1016/j.anai.2024.03.022 -
BMJ (Clinical Research Ed.) Mar 2024To assess the risk of intracranial meningioma associated with the use of selected progestogens.
OBJECTIVE
To assess the risk of intracranial meningioma associated with the use of selected progestogens.
DESIGN
National case-control study.
SETTING
French National Health Data System (ie, ).
PARTICIPANTS
Of 108 366 women overall, 18 061 women living in France who had intracranial surgery for meningioma between 1 January 2009 and 31 December 2018 (restricted inclusion periods for intrauterine systems) were deemed to be in the case group. Each case was matched to five controls for year of birth and area of residence (90 305 controls).
MAIN OUTCOME MEASURES
Selected progestogens were used: progesterone, hydroxyprogesterone, dydrogesterone, medrogestone, medroxyprogesterone acetate, promegestone, dienogest, and intrauterine levonorgestrel. For each progestogen, use was defined by at least one dispensation within the year before the index date (within three years for 13.5 mg levonorgestrel intrauterine systems and five years for 52 mg). Conditional logistic regression was used to calculate odds ratio for each progestogen meningioma association.
RESULTS
Mean age was 57.6 years (standard deviation 12.8). Analyses showed excess risk of meningioma with use of medrogestone (42 exposed cases/18 061 cases (0.2%) 79 exposed controls/90 305 controls (0.1%), odds ratio 3.49 (95% confidence interval 2.38 to 5.10)), medroxyprogesterone acetate (injectable, 9/18 061 (0.05%) 11/90 305 (0.01%), 5.55 (2.27 to 13.56)), and promegestone (83/18 061 (0.5%) 225/90 305 (0.2 %), 2.39 (1.85 to 3.09)). This excess risk was driven by prolonged use (≥one year). Results showed no excess risk of intracranial meningioma for progesterone, dydrogesterone, or levonorgestrel intrauterine systems. No conclusions could be drawn concerning dienogest or hydroxyprogesterone because of the small number of individuals who received these drugs. A highly increased risk of meningioma was observed for cyproterone acetate (891/18 061 (4.9%) 256/90 305 (0.3%), odds ratio 19.21 (95% confidence interval 16.61 to 22.22)), nomegestrol acetate (925/18 061 (5.1%) 1121/90 305 (1.2%), 4.93 (4.50 to 5.41)), and chlormadinone acetate (628/18 061 (3.5%) 946/90 305 (1.0%), 3.87 (3.48 to 4.30)), which were used as positive controls for use.
CONCLUSIONS
Prolonged use of medrogestone, medroxyprogesterone acetate, and promegestone was found to increase the risk of intracranial meningioma. The increased risk associated with the use of injectable medroxyprogesterone acetate, a widely used contraceptive, and the safety of levonorgestrel intrauterine systems are important new findings.
Topics: Female; Humans; Middle Aged; Progestins; Progesterone; Levonorgestrel; Meningioma; Medroxyprogesterone Acetate; Dydrogesterone; Medrogestone; Promegestone; Case-Control Studies; Meningeal Neoplasms
PubMed: 38537944
DOI: 10.1136/bmj-2023-078078 -
PloS One 2024Observational data suggest lower HIV risk with norethisterone enanthate (NET-EN) than with depo-medroxyprogesterone acetate intramuscular (DMPA-IM) injectable... (Randomized Controlled Trial)
Randomized Controlled Trial
Effects of injectable contraception with depot medroxyprogesterone acetate or norethisterone enanthate on estradiol levels and menstrual, psychological and behavioral measures relevant to HIV risk: The WHICH randomized trial.
BACKGROUND
Observational data suggest lower HIV risk with norethisterone enanthate (NET-EN) than with depo-medroxyprogesterone acetate intramuscular (DMPA-IM) injectable contraceptives. If confirmed, a switch between these similar injectable methods would be programmatically feasible and could impact the trajectory of the HIV epidemic. We aimed in this paper to investigate the effects of DMPA-IM and NET-EN on estradiol levels, measures of depression and sexual activity and menstrual effects, relevant to HIV risk; and to ascertain whether these measures are associated with estradiol levels.
METHODS
This open-label trial conducted at two sites in South Africa from 5 November 2018 to 30 November 2019, randomized HIV-negative women aged 18-40 to DMPA-IM 150 mg intramuscular 12-weekly (n = 262) or NET-EN 200 mg intramuscular 8-weekly (n = 259). Data were collected on hormonal, behavioral and menstrual effects at baseline and at 25 weeks (25W).
RESULTS
At 25W, median 17β estradiol levels were substantially lower than at baseline (p<0.001) for both methods: 76.5 pmol/L (interquartile range (IQR) 54.1 to 104.2) in the DMPA-IM group (n = 222), and 69.8 pmol/L (IQR: 55.1 to 89.3) in the NET-EN group (n = 225), with no statistical difference between the two methods (p = 0.450). Compared with DMPA-IM, NET-EN users reported significantly less amenorrhoea, fewer sexual acts, fewer users reporting at least one act of unprotected sex, more condom use with steady partner, more days with urge for sexual intercourse, more days feeling partner does not love her, and more days feeling sad for no reason. We did not find a clear association between estradiol levels and sexual behavior, depression and menstrual effects. Behavioral outcomes suggest less sexual exposure with NET-EN than DMPA-IM. The strength of this evidence is high due to the randomized study design and the consistency of results across the outcomes measured.
CONCLUSIONS
Estradiol levels were reduced to postmenopausal levels by both methods. Secondary outcomes suggesting less sexual exposure with NET-EN are consistent with reported observational evidence of less HIV risk with NET-EN. A randomized trial powered for HIV acquisition is feasible and needed to answer this important question.
TRIAL REGISTRATION
PACTR 202009758229976.
Topics: Humans; Female; Medroxyprogesterone Acetate; Norethindrone; Contraception; Contraceptive Agents, Female; HIV Infections; Estradiol
PubMed: 38530848
DOI: 10.1371/journal.pone.0295764 -
Journal of Public Health in Africa Nov 2023Depot-medroxyprogesterone acetate (DMPA) is a highly effective long acting reversible contraceptive. Alterations in lipid profile have been associated with use of DMPA,...
Depot-medroxyprogesterone acetate (DMPA) is a highly effective long acting reversible contraceptive. Alterations in lipid profile have been associated with use of DMPA, however there is considerable debate about how profound these effects are. Hence the aim of this study is to determine the effect of DMPA on lipid profile and the associated cardiovascular risks. This was a prospective longitudinal study conducted at the family planning clinic of Olabisi Onabanjo University Teaching Hospital Sagamu, Ogun State. Sixty eight new acceptors of DMPA who had their blood samples collected for lipid profile assays at initiation of DMPA, and then at 3 months and 6 months. Data were analyzed using SPSS version 24. After 3 months of DMPA use, there was statistically significant increase in serum Total Cholesterol (TC) concentration (P=0.022), serum Low Density Lipoprotein (LDL) concentration (P=0.033), non significant increase in serum Triglyceride (TG) concentration (P=0.150) and non-significant decrease in serum Higher Density Lipoprotein (HDL) concentration (P=0.076). However, after 6 months of DMPA use, there was statistically significant increase in serum TC concentration (P=0.002), serum LDL concentration (P=0.003), serum TG concentration (P=0.001) and significant decrease in serum HDL concentration (P=0.001). DMPA use is associated with increased serum TC, TG, LDL, and reduction in HDL after 6 months of use. These changes in lipid profile may increase the risk of cardiovascular diseases.
PubMed: 38525248
DOI: 10.4081/jphia.2023.1664 -
Ghana Medical Journal Jun 2023Endometriosis-associated massive haemorrhagic ascites is rare and poses a diagnostic challenge to the gynaecologist due to its resemblance to malignancies, especially...
UNLABELLED
Endometriosis-associated massive haemorrhagic ascites is rare and poses a diagnostic challenge to the gynaecologist due to its resemblance to malignancies, especially ovarian malignancy. We report a 31-year-old nulligravida with progressive abdominal swelling, worsening dysmenorrhea, weight loss and a family history of ovarian tumour. Pelvic ultrasonography and Computed Tomography scans suggested an ovarian mass suspected to be an ovarian malignancy. Exploratory laparotomy revealed massive haemorrhagic ascites (8.6 litre) and multiple nodular masses on the anterior abdominal wall, omentum, bowel and pelvic organs, which were biopsied and confirmed on histopathology to be endometriosis. She had drainage of ascites and hormonal suppression using progestogen (Medroxyprogesterone acetate) with no recurrence in 15 months. Endometriosis should be considered in young, nulligravid women with dysmenorrhea, weight loss and ascites.
FUNDING
None declared.
Topics: Female; Humans; Adult; Ascites; Endometriosis; Dysmenorrhea; Ovarian Neoplasms; Weight Loss
PubMed: 38504753
DOI: 10.4314/gmj.v57i2.12 -
Human Reproduction (Oxford, England) May 2024Is there any difference in ovarian response and embryo ploidy following progesterone-primed ovarian stimulation (PPOS) using micronized progesterone or GnRH antagonist...
Ovarian response and embryo ploidy following oral micronized progesterone-primed ovarian stimulation versus GnRH antagonist protocol. A prospective study with repeated ovarian stimulation cycles.
STUDY QUESTION
Is there any difference in ovarian response and embryo ploidy following progesterone-primed ovarian stimulation (PPOS) using micronized progesterone or GnRH antagonist protocol?
SUMMARY ANSWER
Pituitary downregulation with micronized progesterone as PPOS results in higher number of oocytes retrieved and a comparable number of euploid blastocysts to a GnRH antagonist protocol.
WHAT IS KNOWN ALREADY
Although the GnRH antagonist is considered by most the gold standard protocol for controlling the LH surge during ovarian stimulation (OS) for IVF/ICSI, PPOS protocols are being increasingly used in freeze-all protocols. Still, despite the promising results of PPOS protocols, an early randomized trial reported potentially lower live births in recipients of oocytes resulting following downregulation with medroxyprogesterone acetate as compared with a GnRH antagonist protocol. The scope of the current prospective study was to investigate whether PPOS with micronized progesterone results in an equivalent yield of euploid blastocysts to a GnRH antagonist protocol.
STUDY DESIGN, SIZE, DURATION
In this prospective study, performed between September 2019 to January 2022, 44 women underwent two consecutive OS protocols within a period of 6 months in a GnRH antagonist protocol or in a PPOS protocol with oral micronized progesterone.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Overall, 44 women underwent two OS cycles with an identical fixed dose of rFSH (225 or 300 IU) in both cycles. Downregulation in the first cycles was performed with the use of a flexible GnRH antagonist protocol (0.25 mg per day as soon as one follicle of 14 mm) and consecutively, after a washout period of 1 month, control of LH surge was performed with 200 mg of oral micronized progesterone from stimulation Day 1. After the completion of both cycles, all generated blastocysts underwent genetic analysis for aneuploidy screening (preimplantation genetic testing for aneuplody, PGT-A).
MAIN RESULTS AND THE ROLE OF CHANCE
Comparisons between protocols did not reveal differences between the duration of OS. The hormonal profile on the day of trigger revealed statistically significant differences between protocols in all the tested hormones except for FSH: with significantly higher serum E2 levels, more elevated LH levels and higher progesterone levels in PPOS cycles as compared with antagonist cycles, respectively. Compared with the GnRH antagonist protocol, the PPOS protocol resulted in a significantly higher number of oocytes (12.7 ± 8.09 versus 10.3 ± 5.84; difference between means [DBM] -2.4 [95% CI -4.1 to -0.73]), metaphase II (9.1 ± 6.12 versus 7.3 ± 4.15; DBM -1.8 [95% CI -3.1 to -0.43]), and 2 pronuclei (7.1 ± 4.99 versus 5.7 ± 3.35; DBM -1.5 [95% CI -2.6.1 to -0.32]), respectively. Nevertheless, no differences were observed regarding the mean number of blastocysts between the PPOS and GnRH antagonist protocols (2.9 ± 2.11 versus 2.8 ± 2.12; DBM -0.07 [95% CI -0.67 to 0.53]) and the mean number of biopsied blastocysts (2.9 ± 2.16 versus 2.9 ± 2.15; DBM -0.07 [95% CI -0.70 to 0.56]), respectively. Concerning the euploidy rates per biopsied embryo, a 29% [95% CI 21.8-38.1%] and a 35% [95% CI 26.6-43.9%] were noticed in the PPOS and antagonist groups, respectively. Finally, no difference was observed for the primary outcome, with a mean number of euploid embryos of 0.86 ± 0.90 versus 1.00 ± 1.12 for the comparison of PPOS versus GnRh antagonist.
LIMITATIONS, REASONS FOR CAUTION
The study was powered to detect differences in the mean number of euploid embryos and not in terms of pregnancy outcomes. Additionally, per protocol, there was no randomization, the first cycle was always a GnRH antagonist cycle and the second a PPOS with 1 month of washout period in between.
WIDER IMPLICATIONS OF THE FINDINGS
In case of a freeze-all protocol, clinicians may safely consider oral micronized progesterone to control the LH surge and patients could benefit from the advantages of a medication of oral administration, with a potentially higher number of oocytes retrieved at a lower cost, without any compromise in embryo ploidy rates.
STUDY FUNDING/COMPETING INTEREST(S)
This research was supported by an unrestricted grant from Theramex. N.P.P. has received Research grants from Merck Serono, Organon, Ferring Pharmaceutical, Roche, Theramex, IBSA, Gedeon Richter, and Besins Healthcare; honoraria for lectures from: Merck Serono, Organon, Ferring Pharmaceuticals, Besins International, Roche Diagnostics, IBSA, Theramex, and Gedeon Richter; consulting fees from Merck Serono, Organon, Besins Healthcare, and IBSA. M.d.M.V., F.M., and I.R. declared no conflicts of interest.
TRIAL REGISTRATION NUMBER
The study was registered at Clinical Trials Gov. (NCT04108039).
Topics: Female; Humans; Ovulation Induction; Progesterone; Gonadotropin-Releasing Hormone; Adult; Prospective Studies; Pregnancy; Ploidies; Hormone Antagonists; Blastocyst; Pregnancy Rate; Oocyte Retrieval; Embryo Transfer; Administration, Oral; Sperm Injections, Intracytoplasmic
PubMed: 38498835
DOI: 10.1093/humrep/deae047 -
FP Essentials Mar 2024Short-acting reversible contraceptives (SARCs) are prescribed routinely by primary care clinicians. SARCs are among the most commonly prescribed contraceptive methods...
Short-acting reversible contraceptives (SARCs) are prescribed routinely by primary care clinicians. SARCs are among the most commonly prescribed contraceptive methods and include combined hormonal oral contraceptive pills, the combined hormonal transdermal patch, the combined hormonal vaginal ring, progestin-only pills, and the 3-month depot medroxyprogesterone acetate injection. To ensure safe prescribing and reduce barriers to receiving SARC methods, family physicians should be familiar with two evidence-based national contraceptive guidelines, the (U.S. MEC) and the (U.S. SPR). SARCs have benefits in addition to pregnancy prevention; as such, these methods may be chosen for reasons other than contraception.
Topics: Pregnancy; Female; Humans; Contraceptive Agents; Contraception; Medroxyprogesterone Acetate; Eligibility Determination; Contraceptives, Oral, Hormonal
PubMed: 38498325
DOI: No ID Found