Use Of Progestins Research Articles

Deciphering the divergent roles of progestogens in breast cancer.

Most breast cancers are driven by oestrogen receptor-α. Anti-oestrogenic drugs are the standard treatment for these breast cancers; however, treatment resistance is common, necessitating new therapeutic strategies. Recent preclinical and historical clinical studies support the use of progestogens to activate the progesterone receptor (PR) in breast cancers. However, widespread controversy exists regarding the role of progestogens in this disease, hindering the clinical implementation of PR-targeted therapies. Herein, we present and discuss data at the root of this controversy and clarify the confusion and misinterpretations that have consequently arisen. We then present our view on how progestogens may be safely and effectively used in treating breast cancer.

Introduction: Noncontraceptive use of steroid sex hormones in reproductive medicine.

The use of estrogens and progestins in reproductive medicine is widespread and has spanned decades. Often the effect is therapeutic, but sometimes its use has unintended consequences. In this Views and Reviews, old and new indications for the use of ovarian sex steroids are examined with attention to updating knowledge, breaking bad habits, and providing evidence for use (or nonuse).

Progesterone from maternal circulation binds to progestin receptors in fetal brain.

Steroid hormones activate nuclear receptors which, as transcription factors, can regulate critical aspects of neural development. Many regions of the rat forebrain, midbrain and hindbrain express progestin receptors (PR) during perinatal life, suggesting that progesterone may play an important role in the development of the brain. An immunohistochemical approach using two antibodies with differential recognition of ligand-bound PR was used to examine whether fetuses are exposed to maternal progesterone during pregnancy and whether progesterone from maternal circulation can bind to PR within the fetal brain. Findings demonstrate that maternal and fetal serum progesterone levels are positively correlated at the end of gestation, suggesting a common source of progesterone in mothers and fetuses (e.g., the maternal ovary). Additional findings suggest that administration of exogenous progesterone to mothers not only increases fetal serum progesterone levels within 2 h, but appears to increase ligand-bound PR in fetal brain. These findings suggest that progesterone of maternal origin may play a previously overlooked role in neural development. In addition, there are implications for the ongoing prophylactic use of synthetic progestins in pregnant women for the prevention of premature birth. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 767-774, 2017.

The use of Hormone Therapy after Surgery for Endometriosis: An Analysis

Introduction Estrogen dependence is considered central to the development and progression of endometriosis, which is often viewed as a disease of the premenopausal years, normally regressing after menopause. However, there have been several reports of postmenopausal endometriosis occurring with and without the use of hormone therapy (HT). Objective This review aimed to answer the question of whether it is prudent to offer HT for women with a past history of surgical endometriosis. What are the risks? What type of HT should be given? Methods A review of the medical literature available in Pubmed, EMBASE, Google scholar, Lilacs, Medline and Cochrane Library databases was performed by selecting articles published in the last ten years, written in any language. The keywords used were endometriosis, menopause, and hormone therapy. In all, 36 articles were found from 2006 to 2016, and their potential relevance to this review was examined. We found 20 literature reviews, 2 retrospective studies, 2 randomized controlled trials and 12 case reports. Results There is some risk of endometriosis recurrence after the menopause in patients who receive HT; particularly with estrogen-only therapy. Conclusions The existing literature is inadequate to firmly answer our questions. However it is clear that some risk of recurrence exists. Nevertheless, it is suggested that it is reasonable to prescribe HT to women with a history of surgical endometriosis. Recurrences may occur even in the absence of using HT. It is suggested that in women with severe disease the use of estrogen plus progestogen is safer than estrogen alone. Malignant transformation may occur 1% of the time and may be of greater concern with using estrogen alone, warranting close surveillance in all women.

A randomized double-blind controlled trial of the use of dydrogesterone in women with threatened miscarriage in the first trimester: study protocol for a randomized controlled trial.

BackgroundMiscarriage is a common complication of pregnancy occurring in 15–20 % of all clinically recognized pregnancies. Currently, there is still no good scientific evidence to support the routine use of progestogens for the treatment of threatened miscarriage because the existing studies were not large enough to show a significant difference and some of them were not randomized or double-blind.MethodsThis is a double-blind, randomized controlled trial. A total of 400 patients presenting with first-trimester threatened miscarriage will be enrolled. They will be randomized to take dydrogesterone 40 mg per os, followed by 10 mg per os three times a day or placebo until twelve completed weeks of gestation or 1 week after the bleeding has stopped, whichever is longer. The primary outcome is the percentage of miscarriage before 20 weeks of gestation.DiscussionWe postulate that the dydrogesterone therapy will significantly reduce the risk of miscarriage in women with threatened miscarriage.Trial registrationThis study is registered at ClinicalTrials.gov, NCT02128685. Registered on 29 April 2014.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1509-8) contains supplementary material, which is available to authorized users.

The other side of progestins: effects in the brain.

Progestins are a broad class of progestational agents widely differing in their chemical structures and pharmacological properties. Despite emerging data suggest that progestins, besides their action as endometrial protection, can also have multiple nonreproductive functions, much remains to be discovered regarding the actions exerted by these molecules in the nervous system. Here, we report the role exerted by different progestins, currently used for contraception or in postmenopausal hormone replacement therapies, in regulating cognitive functions as well as social behavior and mood. We provide evidence that the effects and mechanisms underlying their actions are still confusing due to the use of different estrogens and progestins as well as different doses, duration of exposure, route of administration, baseline hormonal status and age of treated women. We also discuss the emerging issue concerning the relevant increase of these substances in the environment, able to deeply affect aquatic wildlife as well as to exert a possible influence in humans, which may be exposed to these compounds via contaminated drinking water and seafood. Finally, we report literature data showing the neurobiological action of progestins and in particular their importance during neurodegenerative events. This is extremely interesting, since some of the progestins currently used in clinical practice exert neuroprotective and anti-inflammatory effects in the nervous system, opening new promising opportunities for the use of these molecules as therapeutic agents for trauma and neurodegenerative disorders.

Adolescent endometriosis

Endometriosis is a common finding in adolescents who have a history of chronic pelvic pain or dysmenorrhoea resistant to medical treatment, however the exact prevalence is unknown. Both early/superficial and advanced forms of endometriosis are found in adolescents, including ovarian endometriomas and deep endometriotic lesions. Whilst spontaneous resolution is possible, recent reports suggest that adolescent endometriosis can be a progressive condition, at least in a significant proportion of cases. It is also claimed that deep endometriosis has its roots in adolescence. Optimum treatment is far from clear and long term recurrence is still a significant problem. The most frequently reported treatment approach in the published literature is a combination of surgery and postoperative hormonal treatment with the combined oral contraceptives, progestins, levonorgestrel intrauterine system or gonadotrophin releasing hormone analogues. Use of gonadotrophin releasing hormone analogues and long term progestins should be carefully considered due to concerns over continuing bone formation in this age group. There is currently no consensus as to whether surgery should be avoided as much as possible to prevent multiple operations in the long term, or surgical treatment should be considered at an early stage before more severe lesions develop. Further research is required to determine which approach would offer a better long term outcome.

Bazedoxifene and Conjugated Equine Estrogen: A Combination Product for the Management of Vasomotor Symptoms and Osteoporosis Prevention Associated with Menopause.

Bazedoxifene (BZA), a third-generation selective estrogen receptor modulator (SERM), has been combined with conjugated equine estrogen (CE) to create a tissue selective estrogen complex (TSEC) for the management of vasomotor symptoms (VMS) and the prevention of osteoporosis (OP) associated with menopause. Both of these outcomes of menopause contribute to significant negative effects on quality of life and increases in utilization of health care resources and dollars. Current treatment modalities for VMS and OP include estrogen therapy that requires the use of progestin in women who have a uterus to reduce the risk of endometrial hyperplasia and resultant cancer. However, progestin use results in nuisance bleeding as well as a further increased risk of breast cancer when combined with estrogen. And while SERMs can be used to prevent OP, their use alone has been shown to increase hot flashes. The combination of BZA and CE does not require progestin treatment with CE as the BZA component acts as an antagonist on endometrial tissue. The U.S. Food and Drug Administration approval of BZA/CE in 2013 was based on a series of five phase 3 studies known as the Selective estrogens, Menopause And Response to Therapy (SMART) trials. These trials, in their entirety, evaluated the impact of BZA/CE on VMS frequency and severity, bone mineral density, bone turnover markers, vaginal symptoms, lipid profiles, sleep, quality of life, breast density, and endometrial safety. The approved dose of BZA/CE is 20 mg BZA and 0.45 mg CE. Although this TSEC manages VMS while opposing breast and endometrial proliferation, preventing bone resorption, and improving lipid profiles, long-term experience with BZA/CE is currently lacking.

Sex hormones and the risk of keratinocyte cancers among women in the United States: A population-based case-control study.

Men are at a higher risk of developing both squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) than women, but there is emerging evidence that women may be experiencing greater increases in the incidence rates of these malignancies than men. One possible explanation is the expanding use of sex steroids among women, although only a few studies have examined this hypothesis. As part of a population-based, case-control study of women in New Hampshire, USA, we sought to evaluate the risk of SCC, BCC, and early-onset BCC in relation to exogenous and endogenous sex hormones. We found that oral contraceptive (OC) use was associated with an increased risk of SCC (OR = 1.4, 95% CI = 1.1-1.8) and BCC (OR = 1.4, 95% CI = 1.0-1.8), particularly high estrogen dose (>50 mg) OC use. Hormone replacement therapy (HRT) use also related to SCC, with an elevated OR largely for progestin use (OR = 1.4, 95% CI = 1.1-1.8). Additionally, both OC use and combination HRT use were associated with more aggressive BCC subtypes. In contrast, menstrual and reproductive history did not appear to influence keratinocyte cancer risk in our data. Our findings provide evidence that use of sex steroids may enhance risk of keratinocyte cancer.

Prevalencia de prescripción conjunta incorrecta de fármacos anticonvulsivantes y anticonceptivos hormonales Colombia, 2014

<p><strong>Objetivo:</strong> determinar la prevalencia de prescripción conjunta de fármacos antiepilépticos para identificar formulación incorrecta que podría afectar la efectividad de los anticonceptivos hormonales en un grupo de mujeres afiliadas al Sistema General de Seguridad Social en Salud de Colombia.</p><p><strong>Materiales y métodos:</strong> estudio de corte transversal, en el que se seleccionaron registros de mujeres de 15 a 45 años que recibían al menos un fármaco antiepiléptico, entre el 1 y el 31 de marzo de 2014, en una base de datos poblacional de dispensación de medicamentos de un operador logístico en Colombia, para población perteneciente al régimen contributivo y subsidiado en el Sistema General de Seguridad Social en Salud de Colombia. Se evaluaron el tipo de anticonceptivo hormonal y de fármaco antiepiléptico. Se utilizó estadística descriptiva.</p><p><strong>Resultados:</strong> de un total de 2092 pacientes usuarias de fármacos antiepilépticos, se identificaron 89 (4,3 %) casos que tenían por lo menos un antiepiléptico y un anticonceptivo simultáneamente. En 48 mujeres (54 %) se encontró formulación incorrecta de métodos de planificación, como el uso de fármacos antiepilépticos inductores enzimáticos e inyectables combinados (20 casos), el uso de anticonceptivos orales combinados de bajas dosis de estrógenos (16 casos), de progestinas orales (10 casos), y el uso de antiepilépticos no inductores enzimáticos y anticonceptivos orales combinados y dosis altas de estrógenos (2 casos).</p><p><strong>Conclusiones:</strong> un importante número de mujeres usuarias de medicamentos antiepilépticos utiliza métodos hormonales de anticoncepción, y cerca de la mitad de ellas tenían una prescripción anticonceptiva incorrecta, lo que podría resultar en embarazos no deseados o incremento del riesgo de enfermedad tromboembólica.</p>

Efficiency of different hormonal treatments for estrus synchronization in tropical Santa Inês sheep.

The aim of this study was to evaluate the effect of (i) the duration of hormone treatment with progestogen sponges during the seasonal anestrus and (ii) the administration of two doses of prostaglandin at 7days apart during the breeding season on reproductive parameters of Santa Inês ewes. In experiment 1, 32 ewes received intravaginal MAP sponges for 6 (G6 days), 9 (G9 days), or 12 (G12days) days and 75μg D-cloprostenol i.m. and 300IU eCG i.m. 1day before sponge removal. In experiment 2, 23 ewes received two doses of 0.48-mg sodium cloprostenol i.m. 7days apart. Ovarian follicular dynamic was assessed through transrectal ultrasonography. Blood samples were collected daily to determine progesterone concentrations. In experiment 1, estrus and ovulation rates did not differ (P > 0.05) among protocols and between cyclic and acyclic ewes at the beginning of the experiment. The G9 days treatment showed a lower dispersion of ovulations in relation to onset of estrus when compared to G6 days and G12 days. In experiment 2, all ewes exhibit estrus and ovulated after the second dose of prostaglandin, although ewes that were in diestrus at D0 showed subluteal concentrations of progesterone during the follicle development stage of the treatment. In conclusion, the use of progestogen device during 9days promotes lower dispersion of ovulation when compared to its use for 6 or 12days, and the protocol of two doses of prostaglandin 7days apart synchronizes estrus efficiently but results in follicular development under low progesterone concentrations.

Progestin and breast cancer risk: a systematic review.

This systematic review summarizes research on the use of progestin and breast cancer risk. Although mainly used for contraception, progestin can help treat menstrual disorders, and benign breast, uterine, and ovarian diseases. Breast cancer is the leading site of new, non-skin, cancers in females in the United States, and possible factors that may modulate breast cancer risk need to be identified. ProQuest (Ann Arbor, MI) and PubMed-Medline (US National Library of Medicine, Bethesda MD, USA) databases were used to search for epidemiologic studies from 2000 to 2015 that examined the association between progestin and breast cancer. Search terms included epidemiologic studies + progesterone or progestin or progestogen or contraceptive or contraceptive agents + breast cancer or breast neoplasms. A total of six studies were included in the review. Five of the six studies reported no association between progestin-only formulations (including norethindrone oral contraceptives, depot medroxyprogesterone acetate, injectable, levonorgestrel system users, implantable and intrauterine devices) and breast cancer risk. Duration of use was examined in a few studies with heterogeneous results. Unlike studies of other oral contraceptives, studies indicate that progestin-only formulations do not increase the risk of breast cancer, although the literature is hampered by small sample sizes. Future research is needed to corroborate these findings, as further understanding of synthetic progesterone may initiate new prescription practices or guidelines for women's health.

Continuous Joint Use of Estrogen and Progestin Decreases Risk of EC in Postmenopausal Women

Continuous Joint Use of Estrogen and Progestin Decreases Risk of EC in Postmenopausal Women

Estrogen Plus Progestin and Lung Cancer: Follow-up of the Women's Health Initiative Randomized Trial

IntroductionIn the Women's Health Initiative (WHI) estrogen plus progestin trial, after 5.6 years' intervention and 8 years' median follow-up, more women died from lung cancer in the hormone therapy group (hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.16-2.52; P = .01). Now after 14 years' median follow-up, we reexamined combined hormone therapy effects on lung cancer mortality. Patients and MethodsIn the WHI placebo-controlled trial, 16,608 postmenopausal women aged 50 to 79 years and with an intact uterus were randomly assigned to once-daily 0.625 mg conjugated equine estrogen plus 2.5 mg medroxyprogesterone acetate (n = 8506) or placebo (n = 8102). Incidence and mortality rates for lung cancer were assessed from multivariant proportional hazard models. ResultsAfter 14 years' cumulative follow-up, there were 219 lung cancers (0.19% per year) in the estrogen plus progestin group and 184 (0.17%) in the placebo group (HR, 1.12; 95% CI, 0.92-1.37; P = .24). While there were more deaths from lung cancer with combined hormone therapy (153 [0.13%] vs. 132 [0.12%], respectively), the difference was not statistically significant (HR, 1.09; 95% CI, 0.87-1.38; P = .45). The statistically significant increase in deaths from lung cancer observed during intervention in women assigned to estrogen plus progestin was attenuated after discontinuation of study pills (linear trend over time, P = .042). ConclusionThe increased risk of death from lung cancer observed during estrogen plus progestin use was attenuated after discontinuation of combined hormone therapy.

A systematic review and meta-analysis of progestogen use for maintenance tocolysis after preterm labor in women with intact membranes.

The use of progestogens for maintenance tocolysis remains controversial, with randomized controlled trials having conflicting results on their efficacy. To evaluate the use of progestational agents for maintenance tocolysis after preterm labor in a systematic review of randomized controlled trials. Electronic databases were searched for reports published before December 2014. Keywords included "tocolysis," "progesterone," "preterm labor," "17-alpha-hydroxyprogesterone," and "vaginal progesterone." Only randomized controlled trials involving progestational agents for maintenance tocolysis were included. Outcomes were analyzed on an intent-to-treat basis and meta-analysis was performed where appropriate. Relative risks and mean differences with 95% confidence intervals were calculated. Four studies (362 women) were included. There were no significant differences between progestational agents and placebo/no treatment in terms of delivery before 34weeks or before 37weeks of pregnancy, time from randomization to delivery, and respiratory distress syndrome. Progestogens were associated with an increase in the neonatal birth weight (mean difference 203.32g, 95% confidence interval 110.85-295.80; P=0.032). The current evidence does not support the routine use of progestational agents for maintenance tocolysis after an episode of preterm labor.

Progestins Upregulate FKBP51 Expression in Human Endometrial Stromal Cells to Induce Functional Progesterone and Glucocorticoid Withdrawal: Implications for Contraceptive- Associated Abnormal Uterine Bleeding.

Use of long-acting progestin only contraceptives (LAPCs) offers a discrete and highly effective family planning method. Abnormal uterine bleeding (AUB) is the major side effect of, and cause for, discontinuation of LAPCs. The endometria of LAPC-treated women display abnormally enlarged, fragile blood vessels, decreased endometrial blood flow and oxidative stress. To understanding to mechanisms underlying AUB, we propose to identify LAPC-modulated unique gene cluster(s) in human endometrial stromal cells (HESCs). Protein and RNA isolated from cultured HESCs treated 7 days with estradiol (E2) or E2+ medroxyprogesterone acetate (MPA) or E2+ etonogestrel (ETO) or E2+ progesterone (P4) were analyzed by quantitative Real-time (q)-PCR and immunoblotting. HSCORES were determined for immunostained-paired endometria of pre-and 3 months post-Depot MPA (DMPA) treated women and ovariectomized guinea pigs (GPs) treated with placebo or E2 or MPA or E2+MPA for 21 days. In HESCs, whole genome analysis identified a 67 gene group regulated by all three progestins, whereas a 235 gene group was regulated by E2+ETO and E2+MPA, but not E2+P4. Ingenuity pathway analysis identified glucocorticoid receptor (GR) activation as one of upstream regulators of the 235 MPA and ETO-specific genes. Among these, microarray results demonstrated significant enhancement of FKBP51, a repressor of PR/GR transcriptional activity, by both MPA and ETO. q-PCR and immunoblot analysis confirmed the microarray results. In endometria of post-DMPA versus pre-DMPA administered women, FKBP51 expression was significantly increased in endometrial stromal and glandular cells. In GPs, E2+MPA or MPA significantly increased FKBP51 immunoreactivity in endometrial stromal and glandular cells versus placebo- and E2-administered groups. MPA or ETO administration activates GR signaling and increases endometrial FKBP51 expression, which could be one of the mechanisms causing AUB by inhibiting PR and GR-mediated transcription. The resultant PR and/or GR-mediated functional withdrawal may contribute to associated endometrial inflammation, aberrant angiogenesis, and bleeding.

Abstract PR10: Menopausal female hormone use in relation to risk of estrogen receptor positive and estrogen receptor negative breast cancer in African American women: Findings from the AMBER consortium

Abstract Background: Previous studies, mostly of white women, have found that female hormone supplements, particularly medications that combine estrogen with progestin, are associated with an increased risk of breast cancer. We examined the use of estrogen alone and estrogen combined with progestin in relation to risk of estrogen receptor-positive (ER+) and ER-negative (ER-) breast cancer in a large combined analysis of data from African American women. Methods: Questionnaire data from two cohort (Black Women's Health Study, Multiethnic Cohort Study) and two case-control (Carolina Breast Cancer Study, Women's Circle of Health Study) studies of breast cancer in African American women were harmonized as part of the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium. Female hormone use was examined among post-menopausal women age 40 and older. ER+ (n=1,486) and ER- (n=638) cases were compared with 8,425 controls. Odds ratios (OR) and 95% confidence intervals (CI) were estimated in polytomous logistic regression analysis with adjustment for study, age, year, geographic region, education, age at menopause, type of menopause, body mass index, oral contraceptive use, family history of breast cancer, parity, age at first birth, alcohol use, and smoking. Results: 37% of women had ever used estrogen alone and 17% had ever used estrogen plus progestin. Use of estrogen plus progestin, relative to never use, was associated with increased risk of ER+ breast cancer (OR=1.43, 95% CI 1.22-1.68). ORs were highest for long duration use (10+ years) and for recent use. The positive associations were also stronger in women with body mass index less than 25 and women age 60 and older. Length of time between menopause and initiation of hormone therapy did not modify the association. By contrast, use of estrogen alone was not associated with ER+ cancer (OR=1.02, 95% CI 0.88-1.17). There were no significant associations of estrogen alone or estrogen plus progestin with ER- breast cancer. Conclusions: Use of combination menopausal hormone supplements was associated with increased risk of ER+, but not ER-, breast cancer among African American women. These results are consistent with findings from studies of white women. This abstract was also presented as Poster B42. Citation Format: Emma Viscidi, Lynn Rosenberg, Chi-Chen Hong, Melissa A. Troester, Elisa V. Bandera, Christopher A. Haiman, Laurence N. Kolonel, Andrew F. Olshan, Christine B. Ambrosone, Julie R. Palmer. Menopausal female hormone use in relation to risk of estrogen receptor positive and estrogen receptor negative breast cancer in African American women: Findings from the AMBER consortium. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr PR10.

Progestin therapy in endometriosis.

Progestins are synthetic compounds that mimic the effects of progesteron. For over 50 years, oral progestins have been demonstrated to be effective in the treatment of endometriosis. They were reported to reduce or eliminate pain symptoms in approximately 90% of the patients. Progestins are available in many forms, including oral preparations, injections, subdermal implants and intrauterine systems. Continuous progestin use is an effective therapy for the treatment of painful symptoms associated with endometriosis but there had been no evidence of progestin use being superior to other types of treatment in endometriosis-related pain symptoms.

Cervical pessary placement for prevention of preterm birth in unselected twin pregnancies: a randomized controlled trial

Preterm birth is the leading cause of neonatal death and handicap in survivors. Although twins are found in 1.5% of pregnancies they account for about 25% of preterm births. Randomized controlled trials in singleton pregnancies reported that the prophylactic use of progestogens, cervical cerclage and cervical pessary reduce significantly the rate of early preterm birth. In twin pregnancies, progestogens and cervical cerclage have been shown to be ineffective in reducing preterm birth. The objective of this study was to test the hypothesis that the insertion of a cervical pessary in twin pregnancies would reduce the rate of spontaneous early preterm birth. This was a multicenter, randomized controlled trial inunselected twin pregnancies of cervical pessary placement from 20(+0)-24(+6) weeks' gestation until elective removal or delivery vs. expectant management. Primary outcome was spontaneous birth <34 weeks. Secondary outcomes included perinatal death and a composite of adverse neonatal outcomes (intraventricular haemorrhage, respiratory distress syndrome, retinopathy of prematurity or necrotizing enterocolitis) or need for neonatal therapy (ventilation, phototherapy, treatment for proven or suspected sepsis, or blood transfusion). Analysis was by intention to treat. This trial is registered in the ISRCTN registry, number01096902. A total of 1,180 (56.0%) of the 2,107 eligible women agreed to take part in the trial; 590 received cervical pessary and 590 had expectant management. Two of the former and one of the latter were lost to follow up. There were no significant differences between the pessary and control groups in rates of spontaneous birth <34 weeks (13.6% vs. 12.9%; relative risk 1.054, 95% confidence interval [CI] 0.787-1.413; p=0.722), perinatal death (2.5% vs. 2.7%; relative risk 0.908, 95% CI 0.553-1.491; p=0.702), adverse neonatal outcome (10.0 vs. 9.2%; relative risk 1.094, 95% CI 0.851-1.407; p=0.524) or neonatal therapy (17.9% vs. 17.2%; relative risk 1.040, 95% CI 0.871-1.242; p=0.701). A post hoc subgroup analysis of 214 women with short cervix (≤25 mm) showed no benefit from the insertion of a cervical pessary. In women with twin pregnancy, routine treatment with cervical pessary does not reduce the rate of spontaneous early preterm birth.

Abstract 866: The proportion of breast and gynecological cancers in Australian women that can be attributed to the use of oral contraceptives and hormone replacement therapy

Abstract Introduction: In 2008 The International Agency for Research on Cancer concluded that combined oral contraceptives (OCs) are a cause of cancer of the breast and cervix but decrease the risk of ovarian and endometrial cancer. They also concluded that estrogen-only hormone replacement therapy (HRT) increases the risk of both endometrial and ovarian cancer, while use of estrogen plus progestogen (combined) HRT increases the risks of breast cancer. The level of risk associated with each cancer type varies by duration and recency of use of hormones. Our aim was to calculate the proportion of breast and gynecological cancers arising in Australian women (population attributable fractions - PAF) that could be attributed to these commonly used hormonal medications. Methods: We calculated PAFs using the standard formula, which requires an estimate of the relative risk for each exposure-cancer association and the prevalence of the causal factor in the population. Relative risks were obtained from published pooled or meta-analyses of the associations and prevalence estimates were derived from Australian National Health Survey estimates or other large national studies. For factors inversely associated with cancer we calculated the “prevented fraction” and estimated the number of cancers that were prevented due to exposure to the factor. Results: The estimated PAFs suggested that fewer than 5% of breast and gynecological cancers in Australia in 2010 could be attributed to oral contraceptive use and estimates were similar for HRT use. However, the calculated preventive fractions for oral contraceptives suggested that the numbers of endometrial and ovarian cancers may have been 46% and 24% higher respectively if no Australian women had used OCs. Given combined HRT increases breast cancer risk and breast cancer is much more common than endometrial or ovarian cancer we also assessed the likely effect if all women taking combined HRT instead took estrogen-only HRT. Under this scenario, we estimate the absolute numbers of ovarian and endometrial cancers would increase slightly but the number of breast cancers attributable to HRT use would decrease substantially. Conclusions: Our analyses suggest that the use of combined OCs confers more benefit than harm with respect to cancer incidence, with a small increase in breast/cervical cancer diagnoses weighed against a much larger decrease in numbers of endometrial and ovarian cancers. In contrast, our results indicate that there would be fewer cancers overall if women did not use HRT. When HRT is required, most guidelines recommend that women with a uterus take combined HRT to prevent endometrial cancer. However, our findings suggest that, in terms of total cancer burden, it might be safer for women to avoid progestogens and use estrogen-only HRT for symptom relief. Future studies should examine this possibility. Citation Format: Susan J. Jordan, Louise Wilson, David Whiteman, Penelope Webb, PAF Project Group. The proportion of breast and gynecological cancers in Australian women that can be attributed to the use of oral contraceptives and hormone replacement therapy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 866. doi:10.1158/1538-7445.AM2015-866