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Contraception Mar 2023To synthesize published literature on POP effectiveness and efficacy. (Review)
Review
OBJECTIVES
To synthesize published literature on POP effectiveness and efficacy.
STUDY DESIGN
We searched PubMed Central, PubMed, and the Cochrane library through March 07, 2022. We included articles written in English reporting a Pearl Index or life table rate for pregnancy. We excluded articles only assessing formulations that: were never marketed globally, are only sold in combination with estrogen, are currently sold only for noncontraceptive purposes, or were not given to participants continuously. Four researchers independently extracted data and two analyzed data using Excel and R.
RESULTS
We included 54 studies. Among studies at low or moderate risk of bias, the median Pearl Index rate (the failure rate during typical use) was 1.63 (range 0.00-14.20, IQR 4.03) and the median method failure Pearl Index rate (the failure rate during perfect use) was 0.97 (range 0.40-6.50, IQR 0.68). Excluding the newer formulations, Desogestrel and Drospirenone, which are closer to combined oral contraceptives in that they prevent pregnancy by inhibiting ovulation, the median Pearl Index rate is 2.00 (range 0.00-14.12, IQR 2.5) and the median method failure Pearl Index rate is 1.05 (range 0.00-10.90, IQR 1.38).
CONCLUSIONS
Among studies at low or moderate risk of bias, the median Pearl Index rate during typical POP use was much lower than currently estimated (7.00), while the median perfect use rate was similar to current estimates.
IMPLICATIONS
Future research should investigate the possibility that POPs may be much more effective during typical use than currently believed.
Topics: Pregnancy; Female; Humans; Desogestrel; Progestins; Contraceptives, Oral, Combined; Estrogens; Ovulation
PubMed: 36535414
DOI: 10.1016/j.contraception.2022.109925 -
Expert Review of Clinical Pharmacology Oct 2020The contraceptive activity of synthetic progestins is mediated through three basic mechanisms: (a) An anti-gonadotrophic action leading to the inhibition of ovulation;... (Review)
Review
INTRODUCTION
The contraceptive activity of synthetic progestins is mediated through three basic mechanisms: (a) An anti-gonadotrophic action leading to the inhibition of ovulation; (b) Changes in cervical mucus characteristics that inhibit sperm penetration and (c) desynchronization of the endometrial picture necessary for implantation.
AREAS COVERED
Mechanisms involved in the progestin-induced endometrium desynchronization are individually reviewed for each of the routes of administration and, whenever possible, by individual members of the various families of synthetic progestin derivatives.
EXPERT OPINION
For contraceptive purposes, progestins are today administered through several routes: orally, as injections, subdermally and via the vagina or the uterine cavity. Given this variety of modalities, their effects may differ, depending on the route of administration, concentration reached at the level of the endometrium and the duration of use. These are characterized by inactivation of the endometrium. Progestin-only contraception provides a safe and effective control of fertility regulation, although, they are associated with the problem of endometrial break through bleeding that may lead to discontinuation. Unfortunately, in spite of a major research effort over two decades, there is not, as yet, an established long-term intervention available to manage bleeding irregularities, making mandatory a deeper understanding of the mechanisms involved is required.
Topics: Animals; Contraceptive Agents, Female; Contraceptives, Oral, Hormonal; Endometrium; Female; Humans; Metrorrhagia; Progestins
PubMed: 32903118
DOI: 10.1080/17512433.2020.1821649 -
Obstetrics and Gynecology May 2023To estimate trends in use and outcomes of progestin therapy for premenopausal patients with endometrial intraepithelial neoplasia.
OBJECTIVE
To estimate trends in use and outcomes of progestin therapy for premenopausal patients with endometrial intraepithelial neoplasia.
METHODS
The MarketScan Database was used to identify patients aged 18-50 years with endometrial intraepithelial neoplasia from 2008 to 2020. Primary treatment was classified as hysterectomy or progestin-based therapy. Within the progestin group, treatment was classified as systemic therapy or progestin-releasing intrauterine device (IUD). The trends in use of progestins and the pattern of progestin use were examined. A multivariable logistic regression model was fit to examine the association between baseline characteristics and the use of progestins. The cumulative incidence of hysterectomy, uterine cancer, and pregnancy since initiation of progestin therapy was analyzed.
RESULTS
A total of 3,947 patients were identified. Hysterectomy was performed in 2,149 (54.4%); progestins were used in 1,798 (45.6%). Use of progestins increased from 44.2% in 2008 to 63.4% in 2020 ( P =.002). Among the progestin users, 1,530 (85.1%) were treated with systemic progestin, and 268 (14.9%) were treated with progestin-releasing IUD. Among progestin users, use of IUD increased from 7.7% in 2008 to 35.6% in 2020 ( P <.001). Hysterectomy was ultimately performed in 36.0% (95% CI 32.8-39.3%) of those who received systemic progestins compared with 22.9% (95% CI 16.5-30.0%) of those treated with progestin-releasing IUD ( P <.001). Subsequent uterine cancer was documented in 10.5% (95% CI 7.6-13.8%) of those who received systemic progestins compared with 8.2% (95% CI 3.1-16.6%) of those treated with progestin-releasing IUD ( P =.24). Venous thromboembolic complications occurred in 27 (1.5%) of those treated with progestins; the venous thromboembolism (VTE) rate was similar for oral progestins and progestin-releasing IUD.
CONCLUSION
The rate of conservative treatment with progestins in premenopausal individuals with endometrial intraepithelial neoplasia has increased over time, and among progestin users, progestin-releasing IUD use is increasing. Progestin-releasing IUD use may be associated with a lower rate of hysterectomy and a similar rate of VTE compared with oral progestin therapy.
Topics: Pregnancy; Female; Humans; Progestins; Levonorgestrel; Venous Thromboembolism; Intrauterine Devices; Endometrial Hyperplasia; Uterine Neoplasms; Intrauterine Devices, Medicated
PubMed: 37023446
DOI: 10.1097/AOG.0000000000005124 -
Endocrine Practice : Official Journal... Dec 2022Transgender women take gender-affirming hormone therapy (GAHT) to affirm their gender identity and improve quality of life and well-being. Usually, GAHT in transgender... (Review)
Review
OBJECTIVE
Transgender women take gender-affirming hormone therapy (GAHT) to affirm their gender identity and improve quality of life and well-being. Usually, GAHT in transgender women consists of estrogen plus a testosterone-lowering medication. The use of progestogens in GAHT for transgender women has been a controversial topic due to lack of evidence for benefit and potential for increased harm.
METHODS
A systematic review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using 4 databases (PubMed/MEDLINE, Ovid, and Cochrane). Manuscripts were reviewed from January 2000 to March 2022 to identify effects of progestogens in transgender women over the age of 16 years on breast development, cardiovascular disease, bone density, quality of life, and stroke incidence.
RESULTS
Ten articles were deemed eligible based on specific inclusion and exclusion criteria. Studies analyzing users of cyproterone acetate were also included if there was a comparator group. No relevant studies were found assessing stroke incidence in the transgender population using a progestogen compound.
CONCLUSION
Overall, findings were significant for a decreased high-density lipoprotein level and increased thromboembolism risk in transgender women using progestogens. No conclusive evidence was found regarding improved quality of life or breast development. Further research needs to be conducted assessing the effects of progestogens in transgender women.
Topics: Male; Female; Humans; Adolescent; Gender Identity; Progestins; Quality of Life
PubMed: 36007714
DOI: 10.1016/j.eprac.2022.08.012 -
The Cochrane Database of Systematic... Jun 2023Premenstrual syndrome (PMS) is a common problem. Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome. Combined oral contraceptives (COC),... (Review)
Review
BACKGROUND
Premenstrual syndrome (PMS) is a common problem. Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome. Combined oral contraceptives (COC), which provide both progestin and oestrogen, have been examined for their ability to relieve premenstrual symptoms. A combined oral contraceptive containing drospirenone and a low oestrogen dose has been approved for treating PMDD in women who choose combined oral contraceptives for contraception.
OBJECTIVES
To evaluate the effectiveness and safety of COCs containing drospirenone in women with PMS.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility Group trial register, CENTRAL (now containing output from two trials registers and CINAHL), MEDLINE, Embase, PsycINFO, LILACS, Google Scholar, and Epistemonikos on 29 June 2022. We checked included studies' reference lists and contacted study authors and experts in the field to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCT) that compared COCs containing drospirenone with placebo or with another COC for treatment of women with PMS.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures recommended by Cochrane. The primary review outcomes were effects on premenstrual symptoms that were prospectively recorded, and withdrawal due to adverse events. Secondary outcomes included effects on mood, adverse events, and response rate to study medications.
MAIN RESULTS
We included five RCTs (858 women analysed, most diagnosed with PMDD). The evidence was very low to moderate quality; the main limitations were serious risk of bias due to poor reporting of study methods, and serious inconsistency and imprecision. COCs containing drospirenone and ethinylestradiol (EE) versus placebo COCs containing drospirenone and EE may improve overall premenstrual symptoms (standardised mean difference (SMD) -0.41, 95% confidence interval (CI) -0.59 to -0.24; 2 RCTs, N = 514; I = 64%; low-quality evidence); and functional impairment due to premenstrual symptoms in terms of productivity (mean difference (MD) -0.31, 95% CI -0.55 to -0.08; 2 RCTs, N = 432; I = 47%; low-quality evidence), social activities (MD -0.29, 95% CI -0.54 to -0.04; 2 RCTs, N = 432; I = 53%; low-quality evidence), and relationships (MD -0.30, 95% CI -0.54 to -0.06; 2 RCTs, N = 432; I = 45%; low-quality evidence). The effects from COCs containing drospirenone may be small to moderate. COCs containing drospirenone and EE may increase withdrawal from trials due to adverse effects (odds ratio (OR) 3.41, 95% CI 2.01 to 5.78; 4 RCT, N = 776; I = 0%; low-quality evidence). This suggests that if you assume the risk of withdrawal due to adverse effects from placebo is 3%, the risk from drospirenone plus EE will be between 6% and 16%. We are uncertain of the effect of drospirenone plus EE on premenstrual mood symptoms, when measured by validated tools that were not developed to assess premenstrual symptoms. COCs containing drospirenone may lead to more adverse effects in total (OR 2.31, 95% CI 1.71 to 3.11; 3 RCT, N = 739; I = 0%; low-quality evidence). This suggests that if you assume the risk of having adverse effects from placebo is 28%, the risk from drospirenone plus EE will be between 40% and 54%. It probably leads to more breast pain, and may lead to more nausea, intermenstrual bleeding, and menstrual disorder. Its effect on nervousness, headache, asthenia, and pain is uncertain. There was no report of any rare but serious adverse effects, such as venous thromboembolism in any of the included studies. COCs containing drospirenone may improve response rate (OR 1.65, 95% CI 1.13 to 2.40; 1 RCT, N = 449; I not applicable; low-quality evidence). This suggests that if you assume the response rate from placebo is 36%, the risk from drospirenone plus EE will be between 39% and 58%. We did not identify any studies that compared COCs containing drospirenone with other COCs.
AUTHORS' CONCLUSIONS
COCs containing drospirenone and EE may improve premenstrual symptoms that result in functional impairments in women with PMDD. The placebo also had a significant effect. COCs containing drospirenone and EE may lead to more adverse effects compared to placebo. We do not know whether it works after three cycles, helps women with less severe symptoms, or is better than other combined oral contraceptives that contain a different progestogen.
Topics: Female; Humans; Contraceptives, Oral, Combined; Drug-Related Side Effects and Adverse Reactions; Estrogens; Premenstrual Dysphoric Disorder; Premenstrual Syndrome; Progestins
PubMed: 37365881
DOI: 10.1002/14651858.CD006586.pub5 -
The Medical Letter on Drugs and... Aug 2020
Review
Topics: Animals; Cimicifuga; Dehydroepiandrosterone; Estrogens; Female; Flax; Hot Flashes; Humans; Menopause; Progestins; Tamoxifen
PubMed: 32960867
DOI: No ID Found -
BJOG : An International Journal of... Jan 2023Fifteen percent of patients with endometrial cancer (EC) have advanced stage disease or develop a recurrence. Progestins have been applied as systemic treatment for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fifteen percent of patients with endometrial cancer (EC) have advanced stage disease or develop a recurrence. Progestins have been applied as systemic treatment for decades, but there is limited evidence on response prediction with biomarkers and toxicity.
OBJECTIVES
To review the response and toxicity of progestin therapy and stratify response to progesterone receptor (PR) expression and tumour grade.
SEARCH STRATEGY
We used the search terms 'Endometrial cancer', 'Progestins', 'Disease progression', 'Recurrence' and related terms in Pubmed, Embase and Cochrane databases.
SELECTION CRITERIA
Studies on patients with advanced stage or recurrent EC treated with progestin monotherapy were included. Studies on adjuvant therapy, with fewer than ten cases and with sarcoma histology were excluded.
DATA COLLECTION AND ANALYSIS
Evaluation for bias was performed with the Revised Cochrane RoB2 tool for randomised studies and the ROBINS-I tool for non-randomised studies. A random effects meta-analysis was performed with the overall response rate (ORR), clinical benefit rate and toxicity as primary outcome measures.
MAIN RESULTS
Twenty-six studies (1639 patients) were included. The ORR of progestin therapy was 30% (95% CI 25-36), the clinical benefit rate was 52% (95% CI 42-61). In PR-positive EC, the ORR was 55%, compared with 12% in PR-negative disease (risk difference 43%, 95% CI 15-71). Severe toxicity occurred in 6.5%.
CONCLUSIONS
Progestin therapy is a viable treatment option in patients with advanced stage and recurrent EC with low toxicity and high ORR in PR-positive disease. The role of PR expression in relation to progression-free survival and overall survival is unclear.
Topics: Female; Humans; Progestins; Neoplasm Recurrence, Local; Endometrial Neoplasms
PubMed: 36264251
DOI: 10.1111/1471-0528.17331 -
The European Journal of Contraception &... Dec 2023abnormal uterine bleeding is a very frequent reason for referral to gynaecologists and can deeply influence the quality of life. Once organic causes requiring surgical... (Review)
Review
BACKGROUND
abnormal uterine bleeding is a very frequent reason for referral to gynaecologists and can deeply influence the quality of life. Once organic causes requiring surgical treatment are ruled out, clinicians should be able to manage these patients conservatively in the most effective way.
MATERIALS AND METHODS
a search in PubMed/MEDLINE database was conducted in order to find relevant and recent meaningful sources for this narrative review.
RESULTS
LNG-IUS 52 mg is the first-line treatment for non-organic causes. Nevertheless, it could be contraindicated or declined by the patient. Combined oral contraceptives (COC) and progestin-only pills inhibit the hypothalamic-pituitary-ovarian axis, preventing ovulation, and induce endometrial atrophy. Consequently, they are effective in treating AUB. Moreover, brand new pills containing a combination of oestrogens, progestins and GnRH antagonists are now available for the management of AUB related to uterine fibroids.
CONCLUSIONS
In daily clinical practice, oral hormonal therapies are convenient and reversible tools to manage AUB when LNG-IUS 52 mg is contraindicated or turn down by the patient. Many oral hormonal therapies are prescribed to treat AUB, but only a few have been approved with this specific indication, therefore further large well-designed studies are necessary in order to compare the efficacy of different pills for treating AUB.
Topics: Female; Humans; Quality of Life; Progestins; Menorrhagia; Contraceptives, Oral, Combined; Leiomyoma; Uterine Hemorrhage; Levonorgestrel
PubMed: 37955241
DOI: 10.1080/13625187.2023.2270098 -
Minerva Obstetrics and Gynecology Dec 2021Short-term and long-term steroid contraceptive systems are widely employed in adolescents and premenopausal women; they could induce variation in bone metabolism, but...
INTRODUCTION
Short-term and long-term steroid contraceptive systems are widely employed in adolescents and premenopausal women; they could induce variation in bone metabolism, but whether these changes increase the overall fracture risk is not yet clear.
EVIDENCE ACQUISITION
A systematic search of scientific publications about "hormonal contraceptives" and "bone metabolism" in reproductive age women was conducted.
EVIDENCE SYNTHESIS
In adolescent girl, combined oral contraceptives could have a deleterious effect on bone health when their onset is within three years after menarche and when they contain ethinyl estradiol at the dose of 20 mcg. In perimenopausal women, steroid contraceptives seem not influence bone health nor increase osteoporotic fractures risk in menopause. The oral progestogens intake is not related to negative effects on skeletal health. Depot medroxyprogesterone acetate (DMPA) induce a prolonged hypoestrogenism with secondary detrimental effect on healthy bone; the higher bone loss was observed at the DMPA dose of 150 mg intramuscular such as after long-term DMPA-users. Progestin-based implants and intrauterine devices have not negative effect on bone health.
CONCLUSIONS
Since sex-steroid drugs induce variations in hormonal circulating concentrations, they may negatively affect bone metabolism. Contraceptive choice should be tailored evaluating any possible effect on bone health. Clinicians should always perform a precontraceptive counselling to identify any coexisting condition that may affect bone health. Further randomized studies are needed to confirm these results.
Topics: Adolescent; Bone Density; Bone and Bones; Female; Hormonal Contraception; Humans; Medroxyprogesterone Acetate; Progestins
PubMed: 34905875
DOI: 10.23736/S2724-606X.20.04688-2 -
The Cochrane Database of Systematic... Feb 2023The copper intrauterine device (Cu-IUD) is a highly effective method of contraception that can also be used for emergency contraception (EC). It is the most effective...
BACKGROUND
The copper intrauterine device (Cu-IUD) is a highly effective method of contraception that can also be used for emergency contraception (EC). It is the most effective form of EC, and is more effective than other existing oral regimens also used for EC. The Cu-IUD provides the unique benefit of providing ongoing contraception after it is inserted for EC; however, uptake of this intervention has been limited. Progestin IUDs are a popular method of long-acting, reversible contraception. If these devices were also found to be effective for EC, they would provide a critical additional option for women. These IUDs could not only provide EC and ongoing contraception, but additional non-contraceptive benefits, including a reduction in menstrual bleeding, cancer prevention, and pain management.
OBJECTIVES
To examine the safety and effectiveness of progestin-containing IUDs for emergency contraception, compared with copper-containing IUDs, or compared with dedicated oral hormonal methods.
SEARCH METHODS
We considered all randomized controlled trials and non-randomized studies of interventions that compared outcomes for individuals seeking a levonorgestrel IUD (LNG-IUD) for EC to a Cu-IUD or dedicated oral EC method. We considered full-text studies, conference abstracts, and unpublished data. We considered studies irrespective of their publication status and language of publication.
SELECTION CRITERIA
We included studies comparing progestin IUDs with copper-containing IUDs, or oral EC methods for emergency contraception.
DATA COLLECTION AND ANALYSIS
We systematically searched nine medical databases, two trials registries, and one gray literature site. We downloaded all titles and abstracts retrieved by electronic searching to a reference management database, and removed duplicates. Three review authors independently screened titles, abstracts, and full-text reports to determine studies eligible for inclusion. We followed standard Cochrane methodology to assess risk of bias, and analyze and interpret the data. We used GRADE methodology to assess the certainty of the evidence.
MAIN RESULTS
We included only one relevant study (711 women); a randomized, controlled, non-inferiority trial comparing LNG-IUDs to Cu-IUDs for EC, with a one-month follow-up. With one study, the evidence was very uncertain for the difference in pregnancy rates, failed insertion rates, expulsion rates, removal rates and the difference in the acceptability of the IUDs. There was also uncertain evidence suggesting the Cu-IUD may slightly increase rates of cramping and the LNG-IUD may slightly increase bleeding and spotting days. AUTHORS' CONCLUSIONS: This review is limited in its ability to provide definitive evidence regarding the LNG-IUD's equivalence, superiority, or inferiority to the Cu-IUD for EC. Only one study was identified in the review, which had possible risks of bias related to randomization and rare outcomes. Additional studies are needed to provide definitive evidence related to the effectiveness of the LNG-IUD for EC.
Topics: Female; Humans; Pregnancy; Contraception, Postcoital; Copper; Intrauterine Devices; Intrauterine Devices, Copper; Progestins; Randomized Controlled Trials as Topic; Steroids
PubMed: 36847591
DOI: 10.1002/14651858.CD013744.pub2