-
Scientific Reports Jan 2023To identify biomarkers of hormonal contraceptive (HC) use in urine and saliva, we conducted a pilot study with 30 women initiating levonorgestrel (LNG) containing...
To identify biomarkers of hormonal contraceptive (HC) use in urine and saliva, we conducted a pilot study with 30 women initiating levonorgestrel (LNG) containing combined oral contraceptives (COCs) or depot medroxyprogesterone acetate (DMPA) (15/group). Based on established COC pharmacokinetics, we collected serum and urine samples before COC ingestion and during Days one and three of use, or before DMPA injection and on Days 21 and 60 post-injection. We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to measure serum/urine LNG and MPA. LNG was undetectable at baseline (specificity 100%); post ingestion, most urine samples had detectable LNG levels (sensitivity: 80% 6 h post Dose one, 93% 6 h post Dose three). We used a DetectX LNG immunoassay kit and showed 100% sensitivity measuring urine LNG. Urine MPA levels were undetectable in 14/15 women at baseline (specificity 91%); post-injection all urine samples had detectable MPA levels (sensitivity: 100% days 21 and 60). Results suggest urine sampling can be used to identify a biomarker of LNG and MPA use. Based on evidence from other steroidal hormonal studies showing changes affecting the transcriptome profile of saliva at 24 h, we used the same (COC, DMPA) timepoints to collect saliva. We performed transcriptome analysis and detected several differentially expressed genes in DMPA users' saliva on Days 21 and 60 compared to baseline; none among COC users. We plan further research of differential gene expression in saliva as a HC biomarker of DMPA use, and will explore longer periods of COC use and saliva collection times, and application of microRNA sequencing to support using saliva as a COC biomarker.
Topics: Female; Humans; Chromatography, Liquid; Pilot Projects; Tandem Mass Spectrometry; Levonorgestrel; Medroxyprogesterone Acetate; Contraceptives, Oral, Combined
PubMed: 36604469
DOI: 10.1038/s41598-022-24215-4 -
Obstetrics and Gynecology Mar 2016To examine the effect of hormonal contraception on sexual desire.
OBJECTIVE
To examine the effect of hormonal contraception on sexual desire.
MATERIALS AND METHODS
We performed a cross-sectional analysis of 1,938 of the 9,256 participants enrolled in the Contraceptive CHOICE Project. This subset included participants enrolled between April and September 2011 who completed a baseline and 6-month telephone survey. Multivariable logistic regression was used to assess the association between contraceptive method and report of lacking interest in sex controlling for potential confounding variables.
RESULTS
More than 1 in 5 participants (23.9%) reported lacking interest in sex at 6 months after initiating a new contraceptive method. Of 262 copper intrauterine device (IUD) users (referent group), 18.3% reported lacking interest in sex. Our primary outcome was more prevalent in women who were young (younger than 18 years: adjusted odds ratio [OR] 2.04), black (adjusted OR 1.78), and married or living with a partner (adjusted OR 1.82). Compared with copper IUD users, participants using depot medroxyprogesterone (adjusted OR 2.61, 95% confidence interval [CI] 1.47-4.61), the vaginal ring (adjusted OR 2.53, 95% CI 1.37-4.69), and the implant (adjusted OR 1.60, 95% CI 1.03-2.49) more commonly reported lack of interest in sex. We found no association between use of the hormonal IUD, oral contraceptive pill, and patch and lack of interest in sex.
CONCLUSION
CHOICE participants using depot medroxyprogesterone acetate, the contraceptive ring, and implant were more likely to report a lack of interest in sex compared with copper IUD users. Future research should confirm these findings and their possible physiologic basis. Clinicians should be reassured that most women do not experience a reduced sex drive with the use of most contraceptive methods.
Topics: Adolescent; Adult; Contraception; Contraceptive Agents, Female; Cross-Sectional Studies; Female; Humans; Intrauterine Devices, Copper; Medroxyprogesterone Acetate; Sexual Dysfunctions, Psychological; Young Adult
PubMed: 26855094
DOI: 10.1097/AOG.0000000000001286 -
Fertility and Sterility Apr 2021To evaluate the pharmacokinetics and pharmacodynamics of medroxyprogesterone acetate after a single subcutaneous injection in the abdomen of 150 or 300 mg Depo-Provera... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To evaluate the pharmacokinetics and pharmacodynamics of medroxyprogesterone acetate after a single subcutaneous injection in the abdomen of 150 or 300 mg Depo-Provera and compare results to two injections of Depo-SubQ Provera 104 given 3 months apart.
DESIGN
Partially randomized, multicenter, parallel-group study.
SETTING
Research unit.
PATIENT(S)
Forty-two women of reproductive age with confirmed ovulatory cycle and body mass index of 18-35 kg/m.
INTERVENTION(S)
Women received a single subcutaneous injection of 150 mg (n = 24) or 300 mg (n = 9) of Depo-Provera or two injections of Depo-SubQ Provera 104 (n = 9).
MAIN OUTCOME MEASURE(S)
Suppression of ovulation as measured by progesterone, serum medroxyprogesterone acetate concentrations, and estimated pharmacokinetics parameters.
RESULT(S)
No ovulations were observed during 7 months after a single injection of 150 or 300 mg Depo-Provera. The 150 mg group had a similar C as observed over two injection cycles of Depo-SubQ Provera 104 and a similar 6-month trough concentration as the 3-month trough of Depo-SubQ Provera 104.
CONCLUSION(S)
Our pharmacodynamics and pharmacokinetics data provide proof of concept that Depo-Provera (150 mg) may be an effective contraceptive method when injected subcutaneously every 6 months, with up to a 4-week grace period for reinjections.
CLINICAL TRIAL REGISTRATION NUMBER
NCT02456584.
Topics: Adult; Contraceptive Agents, Female; Female; Humans; Injections, Subcutaneous; Medroxyprogesterone Acetate; Ovulation
PubMed: 33485608
DOI: 10.1016/j.fertnstert.2020.11.002 -
Steroids Jun 2022The glucocorticoid receptor (GR) regulates transcription of genes involved in multiple processes. Medroxyprogesterone acetate (MPA), widely used in the injectable...
The glucocorticoid receptor (GR) regulates transcription of genes involved in multiple processes. Medroxyprogesterone acetate (MPA), widely used in the injectable contraceptive Depo-MPA (DMPA), has off-target effects via the GR, which may result in side-effects in endocrine therapy. However, very little is known about the GR activity of other progestins used in endocrine therapy. This study compared GR activities for several progestins, using whole cell binding, dose-response, and GR phosphorylation assays, in both a cell line model and peripheral blood mononuclear cells (PBMCs). MPA, etonogestrel (ETG) and nestorone (NES) exhibit greater relative binding affinities for the GR than levonorgestrel (LNG) and norethisterone/norethindrone (NET) and are partial GR agonists for transactivation but agonists for transrepression on synthetic promoters in COS-1 cells. MPA is a potent agonist for endogenous GR-regulated GILZ and IL6 genes in PBMCs. While ETG and NES also display agonist activity on IL6, they have little effect on GILZ. In contrast, LNG and NET exhibit little to no activity in transactivation models, while both exhibit some transrepressive activity but are generally less potent and/or efficacious than MPA. Antagonist and phosphorylation assays confirmed that MPA and NES act via the GR on endogenous genes in PBMCs. Our results suggest GR-mediated dose-dependent and gene-specific transcriptional side-effects are likely to occur at physiologically relevant concentrations in vivo for MPA, may possibly occur selectively for ETG and NES, but are unlikely to occur for LNG and NET. This suggests that these progestins will exhibit differential side-effects in endocrine therapy via the GR.
Topics: Animals; COS Cells; Chlorocebus aethiops; Glucocorticoids; Interleukin-6; Leukocytes, Mononuclear; Levonorgestrel; Medroxyprogesterone Acetate; Norethindrone; Progestins; Receptors, Glucocorticoid
PubMed: 35271867
DOI: 10.1016/j.steroids.2022.108998 -
Frontiers in Global Women's Health 2022Hormonal contraception affects endogenous sex steroid levels. Robust evidence from randomized trials of the relative effects of different contraceptive methods is...
Effects of Depot Medroxyprogesterone Acetate Intramuscular Injection, Copper Intrauterine Device and Levonorgestrel Implant Contraception on Estradiol Levels: An Ancillary Study of the ECHO Randomized Trial.
INTRODUCTION
Hormonal contraception affects endogenous sex steroid levels. Robust evidence from randomized trials of the relative effects of different contraceptive methods is scarce. We compared the effects of three contraceptive methods on serum estradiol levels using data from women (18-35 years) requesting contraception in the Evidence for Contraceptive Options and HIV Outcomes (ECHO) randomized trial.
METHODS
Women were randomly allocated to the depot medroxyprogesterone acetate intramuscular (DMPA-IM) injection, copper intrauterine device (IUD) or levonorgestrel (LNG) implant. In this sub-study, stored baseline and 6-month serum samples were analyzed in 401 participants from East London, South Africa (DMPA-IM: 131, IUD: 135 and LNG: 135).
RESULTS
Baseline median (interquartile range, IQR) estradiol levels were similar between the three groups [DMPA-IM 229 (152-455), IUD 235 (168-426) and LNG 216 (153-419 pmol/L)]. At 6-months, median estradiol in the IUD group was unchanged (298 (163-467) pmol/L), whilst levels in the DMPA-IM and implant groups were significantly reduced from baseline. The median estradiol level in the DMPA-IM group [139 (97-193) pmol/L] was significantly lower than in both IUD ( < 0.0001) and implant ( = 0.005) groups; and level in the implant group [156 (112-250) pmol/L] was significantly lower than in the IUD group ( = 0.004).
CONCLUSIONS
At 6-months (DMPA-IM nadir), median estradiol with DMPA-IM was 53% lower and with the LNG implant, 48% lower than with the IUD. The greater reduction in estradiol levels with the DMPA-IM injection compared to the LNG implant and IUD has implications for the relative psychological, sexual as well as physiological side-effects of these contraceptive methods.
ECHO STUDY REGISTRATION
ClinicalTrials.gov, identifier: NCT02550067.
PubMed: 35669313
DOI: 10.3389/fgwh.2022.887541 -
Journal of Human Reproductive Sciences 2022Progesterone-primed ovarian stimulation (PPOS) protocol is based on the principle of preventing pre-mature luteinising hormone surge during ovarian stimulation using...
BACKGROUND
Progesterone-primed ovarian stimulation (PPOS) protocol is based on the principle of preventing pre-mature luteinising hormone surge during ovarian stimulation using progesterone.
AIMS
In this study, we aimed to compare the cost-effectiveness of PPOS over GnRH antagonist cycles in oocyte donor cycles where freeze all is a norm.
SETTINGS AND DESIGN
It is a prospective cohort study with 130 participants.
MATERIALS AND METHODS
We included all women undergoing oocyte donation using PPOS protocol and antagonist protocol at our centre. Fifty-seven belonged to the PPOS group and were given medroxyprogesterone acetate (MPA) and 73 belonged to the GnRH antagonist group who received cetrorelix. The primary outcome was the number of mature oocyte retrieved at OPU and the cost involved per stimulation cycle.
STATISTICAL ANALYSIS USED
For normally distributed observations, we used -test, and for the variables of non-normal distribution, Mann-Whitney -test was used. The significance was accepted for < 0.05.
RESULTS
The baseline clinical characteristics of the donors were comparable with a mean age of 25.42 ± 2.90 years, body mass index of 24.00 ± 4.00 kg/m and antral follicle count of 18.63 ± 5.23. The duration of stimulation was similar in both the groups as well as the total gonadotropin dose required was not significantly different. The number of mature oocytes retrieved was same in both the groups (10.41 ± 4.04 with antagonist and 10.25 ± 3.23 with PPOS, = 0.964). There were no reported cases of severe ovarian hyperstimulation syndrome (OHSS) in any of the groups. The incidence of mild-to-moderate OHSS in the antagonist group was 5.4% and in the PPOS group was 3.6%, and the difference was not significant ( = 0.69). The cost per mature oocyte (M2) was significantly higher in the antagonist protocol in comparison to the PPOS protocol (INR 9485.69 ± 5751.11 vs. Rs. 5945.86 ± 2848.59, respectively, < 0.001).
CONCLUSION
Our study identifies PPOS protocol using MPA to be more cost-effective and patient-friendly than conventional GnRH antagonist protocol in oocyte donor cycles.
PubMed: 36341015
DOI: 10.4103/jhrs.jhrs_85_22 -
Archives of Gynecology and Obstetrics Nov 2023Although many patients with endometrial cancer (EC) or atypical endometrial hyperplasia (AEH) achieve complete remission (CR) after high-dose medroxyprogesterone acetate...
PURPOSE
Although many patients with endometrial cancer (EC) or atypical endometrial hyperplasia (AEH) achieve complete remission (CR) after high-dose medroxyprogesterone acetate (MPA) treatment, no consensus has been reached on management after CR. Currently, patients receive estrogen-progestin maintenance therapy, but no recommendations exist regarding the duration of maintenance therapy or whether hysterectomy should be considered. This study aimed to provide insights into the management of EC/AEH after achieving CR.
METHODS
We retrospectively investigated the prognosis of 50 patients with EC or AEH who achieved CR after MPA therapy. We assessed the association between disease recurrence and clinicopathological features and the pre- and post-operative histological diagnoses of patients who underwent hysterectomy.
RESULTS
The median follow-up duration was 34 months (range: 1-179 months). Recurrence was observed in 17 patients. Among the clinical characteristics investigated, only the primary disease was significantly associated with disease recurrence; patients with EC had a higher risk of recurrence than those with AEH (p = 0.037). During the observation period, 27 patients attempted pregnancy, and 14 pregnancies resulted in delivery. Patients who gave birth had significantly longer relapse-free survivals than those who did not (p = 0.031). Further, 16 patients underwent hysterectomies, and AEH was detected postoperatively in 4 of 11 patients (36.4%) with no preoperative abnormalities.
CONCLUSIONS
We identified several clinical features of patients with EC and AEH after CR. Given the high probability of endometrial abnormalities detected postoperatively, hysterectomy may be considered for patients who no longer want children.
Topics: Pregnancy; Female; Child; Humans; Endometrial Hyperplasia; Retrospective Studies; Fertility Preservation; Treatment Outcome; Neoplasm Recurrence, Local; Endometrial Neoplasms; Medroxyprogesterone Acetate; Prognosis
PubMed: 37310452
DOI: 10.1007/s00404-023-07077-7 -
Medicina (Kaunas, Lithuania) Oct 2022Background and objectives: Abnormal uterine bleeding is a significant clinical and gynaecological concern that necessitates its safe and effective treatment. The present... (Randomized Controlled Trial)
Randomized Controlled Trial
Evaluation of the Safety and Efficacy of Ormeloxifene, a Selective Estrogen Receptor Modulator and Medroxyprogesterone Acetate in Women with Non-Structural Abnormal Uterine Bleeding: A Randomized Clinical Trial.
Background and objectives: Abnormal uterine bleeding is a significant clinical and gynaecological concern that necessitates its safe and effective treatment. The present study aims to compare the cost-effectiveness, safety, efficacy, and health-related quality of life of ormeloxifene with medroxyprogesterone acetate in women with non-structural abnormal uterine bleeding. Materials and Methods: A prospective, randomized, single-blinded clinical trial of 367 patients was carried out at a tertiary care hospital for a period of one year from 5 January 2019 to 4 January 2020. Patients were randomized into two groups for administering ormeloxifene and medroxyprogesterone acetate for a 3-month treatment duration and were evaluated by laboratorial investigations like anaemic status, bleeding duration, endometrial thickness, pictorial blood loss assessment chart (PBLAC) score, and patient’s medical and medication history. Health-related quality of life was assessed using short form survey-36 (SF-36) questionnaire scale. Cost-effectiveness was determined on the basis of the three-month treatment regimen. Results: The mean duration of bleeding reduced from 16.88 ± 6.46 to 7.76 ± 1.55 in the ormeloxifene group and from 15.91 ± 5.04 to 8.7 ± 1.91 (p < 0.001) in the medroxyprogesterone acetate. Similarly, mean haemoglobin increased from 8.56 ± 0.77 to 10.1 ± 0.087 g/dL and from 8.60 ±0.97 to 9.551 ± 0.90 g/dL (p < 0.001), and endometrial thickness showed a reduction from 8.52 ± 1.61 mm to 6.92 ± 1.68 mm and from 8.40 ± 2.09 mm to 7.85 ± 2.0 mm (p < 0.001) in the ormeloxifene and medroxyprogesterone acetate groups, respectively. PBLAC score reduced from 289.92 ± 42.39 to 128.11 ± 33.10 and from 287.38 ± 40.94 to 123.5 ± 29.57 (p < 0.001) in these groups, respectively. Health-related quality of life improved in the ormeloxifene group more than the medroxyprogesterone group, which was evidenced by SF-36 scale parameters (physical function, energy/fatigue and pain) that changed from 24.39, 12.99, 6.25 to 28.95, 18, 9 and from 25.41, 13.6, 7.1 to 27.02, 16, 8.3 in the ormeloxifene and medroxyprogesterone acetate groups, respectively. Conclusions: The study concludes that both medroxyprogesterone acetate and ormeloxifene are safe and efficacious in controlling abnormal uterine bleeding, but ormeloxifene was the better of the two in terms of cost effectiveness, reduction in pictorial blood loss assessment score, endometrial thickness, bleeding duration (days), increase in haemoglobin concentration (g/dL) and improvement in the quality of life.
Topics: Humans; Female; Medroxyprogesterone Acetate; Selective Estrogen Receptor Modulators; Quality of Life; Prospective Studies; Uterine Hemorrhage
PubMed: 36363460
DOI: 10.3390/medicina58111503 -
Frontiers in Oncology 2021Medroxyprogesterone acetate (MPA) is the main conservative treatment for endometrial cancer (EC) patients desirable to preserve fertility and those who...
Medroxyprogesterone acetate (MPA) is the main conservative treatment for endometrial cancer (EC) patients desirable to preserve fertility and those who cannot suffer from surgery. Considering the high incidence of progestin resistance and recurrence of MPA treatment, we reproposed antipsychotics chlorpromazine (CPZ) as a new strategy for both progestin-sensitive and -resistant endometrial cancer. Cytobiology experiments indicated that CPZ could significantly suppress proliferation, migration/invasion and induce apoptosis in Ishikawa (ISK) and KLE EC cell lines. And xenograft mouse models were constructed to validate the antitumor effect and toxicity of CPZ . CPZ inhibited the growth at a low dose of 3mg/kg and the mice exhibited no signs of toxicity. Next, concomitant treatment and sequential treatment with CPZ and MPA were proceeded to analysis the synergistic effect in EC cells. Concomitant treatment only performed a limited synergistic effect on apoptosis in ISK and KLE cells. Nevertheless, sequential treatment showed favorable synergistic effects in progestin-resistant KLE cells. Finally, a stable MPA-resistant cell line shRNA was established to explore the mechanism of CPZ reversing progestin resistance. Immunoblot data showed that CPZ inhibited the activation of PI3K/AKT signal in ISK and KLE cells and upregulated PRB expression in progestin-resistant cells, by which CPZ overcame progestin resistance to MPA. Thus, CPZ might act as a candidate drug for conservative treatment and sequential treatment with CPZ and MPA could be a suitable therapeutic option for progestin resistant patients.
PubMed: 33937078
DOI: 10.3389/fonc.2021.665832 -
BioMed Research International 2022Endometrial cancer (EC) is one of the most common gynecologic malignancy, mostly in postmenopausal women. The gold standard treatment for EC is surgery, but in the early... (Review)
Review
BACKGROUND
Endometrial cancer (EC) is one of the most common gynecologic malignancy, mostly in postmenopausal women. The gold standard treatment for EC is surgery, but in the early stages, it is possible to opt for conservative treatment. In the last decade, different clinical and pathological markers have been studied to identify women who respond to conservative treatment. A lot of immunohistochemical markers have been evaluated to predict response to progestin treatment, even if their usefulness is still unclear; the prognosis of this neoplasm depends on tumor stage, and a specific therapeutic protocol is set according to the stage of the disease.
OBJECTIVE
(1) To provide an overview of the conservative management of Stage 1A Grade (G) 2 endometrioid EC (FIGO) and the oncological and reproductive outcomes related; (2) to describe the molecular alterations before and after progestin therapy in patients undergoing conservative treatment.
MATERIALS AND METHODS
A systematic computerized search of the literature was performed in the main electronic databases (MEDLINE, Embase, Web of Science, PubMed, and Cochrane Library), from 2010 to September 2021, in order to evaluate the oncological and reproductive outcomes in patients with G2 stage IA EC who ask for fertility-sparing treatment. The expression of several immunohistochemical markers was evaluated in pretreatment phase and during the follow-up in relation to response to hormonal therapy. Only scientific publications in English were included. The risk of bias assessment was performed. Review authors' judgments were categorized as "low risk," "high risk," or "unclear risk" of bias.
RESULTS
Twelve articles were included in the study: 7 observational studies and 5 case series/reports. Eighty-four patients who took progestins (megestrol acetate, medroxyprogesterone acetate, and/or levonorgestrel-releasing intrauterine devices) were analyzed. The publication bias analysis turned out to be "low." 54/84 patients had a complete response, 23/84 patients underwent radical surgery, and 20/84 had a relapse after conservative treatment. Twenty-two patients had a pregnancy. The length of follow-up was variable, from 6 to 142 months according to the different studies analyzed. Several clinical and pathological markers have been studied to identify women who do not respond to conservative treatment: PR and ER were the most studied predictive markers, in particular PR appeared as the most promising; MMR, SPAG9, Ki67, and Nrf2-survivin pathway provided good results with a significant association with a good response to progestin therapy. However, no reliable predictive markers are currently available to be used in clinical practice.
CONCLUSIONS
The conservative treatment may be an option for patients with stage IA G2 EEC who desire to preserve their fertility. The immunohistochemical markers evaluation looks promising in predicting response to conservative treatment. Further large series and randomized clinical trials are needed to confirm these results.
Topics: Adaptor Proteins, Signal Transducing; Antineoplastic Agents, Hormonal; Carcinoma, Endometrioid; Endometrial Neoplasms; Female; Fertility Preservation; Humans; Ki-67 Antigen; Levonorgestrel; Medroxyprogesterone Acetate; Megestrol Acetate; NF-E2-Related Factor 2; Neoplasm Recurrence, Local; Pregnancy; Progestins; Survivin
PubMed: 36203482
DOI: 10.1155/2022/4070368