[Additional non-contraceptive effects of contraception: CNGOF Contraception Guidelines]. / Bénéfices non contraceptifs des contraceptions. RPC Contraception CNGOF.

Hormonal and intrauterine contraceptive methods provide women with highly efficient protection against undesired pregnancy. Additional non-contraceptive effects are now well documented. Combined hormonal contraceptives use, either through the oral transdermal and vaginal route, allow a reduction in menorrhagia, dysmenorrhea, functional ovarian cysts, benign breast and uterine disease, endometriosis-related pain and recurrence. A reduction in ovarian cancer risks, including in women with BRCA syndrome, endometrial and colon cancer is documented. This effect is prolonged for years after contraception discontinuation. Non-contraceptive benefits of progestin-only contraceptives are less documented. Use of the levonorgestrel IUD is associated with a reduction in menorrhagia, dysmenorrhea including in case of endometriosis. Copper IUD use is associated with a decrease in cervix and endometrial cancer risk.

Oral hormonal contraception in special circumstances.

BACKGROUND: Despite the general consensus that long-acting reversible contraceptives (LARCs) are the most appropriate choice of contraception for most women, there are special circumstances when the contraceptive and non-contraceptive needs of the patient are met by oral methods. OBJECTIVE: By using case histories, we seek to demonstrate the medical and practical complexities in managing contraceptive needs that may result in oral contraception being the most appropriate choice. The cases also illustrate the resources available to enable evidence-based management. DISCUSSION: Concurrent medical conditions and non-contraceptive benefits of oral contraceptive methods will see the continued use of these medications for a significant minority of women. A comprehensive knowledge of the rapidly developing evidence regarding medical eligibility and indications for usage is required. Reference to the already highly developed and easily accessible evidence bases ensures best practice for the women and families who seek advice.

Impact and mechanistic role of oral contraceptive pills on the number and epithelial type of ovarian cortical inclusion cysts; a clinicopathology and immunohistochemical study.

BACKGROUND: Ovarian epithelial cancers are among the most lethal women's cancers. There is no doubt about the preventive role of oral contraceptive pills (OCPs) in development of ovarian cancers. But, there are limited numbers of studies to address the effect of these agents on the number of cortical inclusion cysts (CICs), their epithelial type and suppression of the metaplastic phenomenon by these pills. The aim of this study was to clarify the role of these agents in the prevention of these cyst formation and tubal metaplasia and also examine the mesenchymal-epithelial transition theory in this context by immunohistochemical methods. METHODS: The representative section(s) of ovarian cortex from a total number of 201 consecutive total abdominal hysterectomy with bilateral or unilateral salpingo-oophorectomy specimens were examined for mean number of CICs and their epithelial type between two groups of the patients. Group A included the patients who were on oral contraceptive pills for more than 5 years. All of the subjects with other contraceptive methods or a history of less than 5 years contraceptive pills usage were stratified in group B. Sections from 20 cases in which more than five inclusion cysts were found, were selected for IHC staining with calretinine and PAX8 as markers for mesothelium and mullerian epithelium respectively. RESULTS: The mean age of the patients was 51.67 years with no significant differences between two groups. The mean number of cysts were 1.27 and 3.23 in group A and B respectively (P =0.0001). Similarly the mean number of CICs, lined by tubal epithelium, was significantly different between two groups (0.65 vs 2.65, P =0.0001). In IHC staining 123 out of 150 CICs (82 %) were PAX+ while only 7 CICs (4.8 %) showed positive reaction for calretinin irrespective of type of epithelium. CONCLUSION: Our findings showed that the use of OCP for more than five years in women, significantly prevents development of cortical inclusion cysts in the ovaries which lined by tubal (PAX8 positive) type epithelium. These findings may explain the alternative mechanism of oral contraceptive pills or long time use of progesterone in suppression of tubal type overgrowth and subsequently prevention of ovarian epithelial cancers.

Steroids pretreatment in assisted reproduction cycles.

The objective is to present an overview of trials and appreciate the relevant data on the effect of steroids pretreatment (oral contraceptives, 17ß-estradiol and estradiol valerate) in assisted reproduction cycles. The subject of the study is to evaluate the clinical characteristics during steroids pretreatment cycles focused on the prevention of ovarian cysts, the positive contraceptive effect on the onset of regular period during long gonadotropin releasing hormone agonist protocol. In gonadotropin releasing hormone antagonist protocol the review is interested in supporting ovarian stimulation in low responders, the idea of cycle scheduling and improving treatment outcomes. The method is a review from MEDLINE/Pubmed database between 1994 and July 2012. We identified 15 randomised controlled trials (n=3069 patients). One trail (n=83 patients) assessed GnRH agonist protocol with or without steroids pretreatment, 8 trials (n=1884 patients) assessed GnRH antagonist protocols with or without steroids pretreatment and 6 trials (n=1102 patients) assessed GnRH antagonist protocols versus agonist ones with steroid pretreatment. Data demonstrates that oral contraceptives offer the effective prevention of functional ovarian cysts, the predictable onset of period during desensitisation. Existing data suggest that pretreatment with oral contraceptive pills or estradiol valerate give no advantage concerning number of oocytes or pregnancy rate. Pretreatment with oral contraceptive pills aiming to avoid weekend oocytes retrievals has to be more elucidated. In low responders oral contraceptive pill pretreatment may be beneficial in improving ovarian responses by reducing the amount of gonadotropins and the number of days required for ovarian stimulation. Current research indicates that also 17ß-estradiol may be encouraging pretreatment in low responders and in cycle scheduling. This article is part of a Special Issue entitled 'Pregnancy and Steroids'.

The BRG1 chromatin remodeler protects against ovarian cysts, uterine tumors, and mammary tumors in a lineage-specific manner.

The BRG1 catalytic subunit of SWI/SNF-related complexes is required for mammalian development as exemplified by the early embryonic lethality of Brg1 null homozygous mice. BRG1 is also a tumor suppressor and, in mice, 10% of heterozygous (Brg1(null/+)) females develop mammary tumors. We now demonstrate that BRG1 mRNA and protein are expressed in both the luminal and basal cells of the mammary gland, raising the question of which lineage requires BRG1 to promote mammary homeostasis and prevent oncogenic transformation. To investigate this question, we utilized Wap-Cre to mutate both Brg1 floxed alleles in the luminal cells of the mammary epithelium of pregnant mice where WAP is exclusively expressed within the mammary gland. Interestingly, we found that Brg1(Wap-Cre) conditional homozygotes lactated normally and did not develop mammary tumors even when they were maintained on a Brm-deficient background. However, Brg1(Wap-Cre) mutants did develop ovarian cysts and uterine tumors. Analysis of these latter tissues showed that both, like the mammary gland, contain cells that normally express Brg1 and Wap. Thus, tumor formation in Brg1 mutant mice appears to be confined to particular cell types that require BRG1 and also express Wap. Our results now show that such cells exist both in the ovary and the uterus but not in either the luminal or the basal compartments of the mammary gland. Taken together, these findings indicate that SWI/SNF-related complexes are dispensable in the luminal cells of the mammary gland and therefore argue against the notion that SWI/SNF-related complexes are essential for cell survival. These findings also suggest that the tumor-suppressor activity of BRG1 is restricted to the basal cells of the mammary gland and demonstrate that this function extends to other female reproductive organs, consistent with recent observations of recurrent ARID1A/BAF250a mutations in human ovarian and endometrial tumors.

The state of hormonal contraception today: established and emerging noncontraceptive health benefits.

In the 50 years since the advent of combined oral contraceptives the amount of estrogen in oral contraceptives dropped from over 100 mcg to less than 30 mcg. Many noncontraceptive health benefits have emerged that decrease mortality and improve quality of life. Some of the immediate benefits include improvement of menorrhagia and dysmenorrhea, reduction in premenstrual dysphoric disorder symptoms, and decreased acne. As an effective birth control method oral contraceptives also decrease pregnancy-related deaths by preventing pregnancy. After the reproductive years, previous use of oral contraceptives continues to be beneficial, reducing the risk of death from ovarian and endometrial cancer. All these benefits have held up over time whereas cardiovascular risks have lessened because of the decrease in oral contraceptive pill dosage. Decreased ovarian cyst formation is an example of benefit with higher-dose oral contraceptive formulations that no longer holds true with low-dose pills.

A randomized controlled trial of NuvaRing versus combined oral contraceptive pills for pretreatment in in vitro fertilization cycles.

OBJECTIVE: To determine whether use of the NuvaRing (Merck) for pretreatment in IVF cycles would result in better cycle control and patient satisfaction versus a 30-µg oral contraceptive (OC) pill. DESIGN: A prospective randomized, controlled study. SETTING: An academic, hospital-based fertility clinic in Toronto, Canada. PATIENT(S): Patients 18-37 years old, undergoing their first IVF or IVF/intracytoplasmic sperm injection (ICSI) cycle. INTERVENTION(S): OC versus NuvaRing for IVF pre-treatment. MAIN OUTCOME MEASURE(S): Patient satisfaction, ovarian suppression, and IVF cycle outcomes. RESULT(S): Demographic data were similar in both groups. There were no significant differences in side effects between the NuvaRing and OC pill group with the exception of more breast discomfort in the OC pill group. There were no differences in the protocols, days of stimulation, and number of oocytes between the groups. Patients in the OC pill group had more embryos on day 3 and more patients had excess embryos for freezing. The number of embryos transferred and clinical pregnancy rates (PR) were similar between the two groups, although more patients in the NuvaRing group had cycles cancelled for poor stimulation. CONCLUSION(S): There was no significant benefit in patient tolerability or side effects with the NuvaRing versus the OC pill for IVF pretreatment; however, side effects overall were low in both groups. Clinical PRs were similar; however, the NuvaRing group had more cancelled cycles and fewer excess embryos for freezing. CLINICAL TRIAL REGISTRATION: #NCT01298128.

Gynecologic conditions in participants in the NSABP breast cancer prevention study of tamoxifen and raloxifene (STAR).

OBJECTIVE: This study reports the gynecologic conditions in postmenopausal women (intact uterus on enrollment) in the National Surgical Adjuvant Breast and Bowel Project (NSABP) study of tamoxifen and raloxifene (STAR)/P-2 trial. STUDY DESIGN: This study, with a median follow-up period of 81 months, evaluated the incidence rates/risks of gynecologic conditions among women who were treated with tamoxifen and raloxifene. RESULTS: Compared with women who received tamoxifen therapy, women who received raloxifene therapy had a lower incidence of uterine cancer (relative risk, 0.55)/endometrial hyperplasia (relative risk, 0.19), leiomyomas (relative risk, 0.55), ovarian cysts (relative risk, 0.60), and endometrial polyps (relative risk, 0.30) and had fewer procedures performed. Women receiving tamoxifen therapy had more hot flashes (P < .0001), vaginal discharge (P < .0001), and vaginal bleeding (P < .0001). CONCLUSION: Our results suggest that tamoxifen has more of an estrogenic effect on the gynecologic reproductive organs. These effects should be considered in counseling women on options for breast cancer prevention.

Non-contraceptive benefits of hormonal contraceptives.

Besides the contraceptive effect of the various hormonal contraceptives, it is intended to demonstrate the non-contraceptive health benefits for treatment and prevention of bleeding problems, menstruation-related pain and other disorders, such as premenstrual syndrome and signs of androgenization. The effectiveness can be improved by choosing the proper progestogen with antiandrogenic action. Treatment but also prevention can be achieved with hormonal contraceptives in benign proliferative diseases of women, such as ovarian cysts, endometriosis, adenomyosis, endometrial hyperplasia, myoma and benign breast disease. Furthermore, hormonal contraceptives such as estrogen/progestogen combinations reduce pelvic inflammatory disease, rheumatoid arthritis, asthma symptoms and preserve bone density. In addition, a major impact in oncological prevention seems to be possible for ovarian, endometrial and colon cancer and these positive preventive effects seem to persist also after discontinuation of hormonal contraceptives. In addition, practical concepts for hormonal contraceptive selection will be outlined.

[Preventive and therapeutic effect of E-leng capsule on post-operation recurrence of ovarian endometriotic cysts and its influence on expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in eutopic and ectopic endometrium].

OBJECTIVE: To investigate the effect and mechanism of E-leng Capsule (ELC) in preventing and treating post-operation recurrence of ovarian endometriotic cysts (OEC). METHODS: A total of 60 patients enrolled were the inpatients, who underwent cystectomy of OEC in the Gynecological Department of Guangdong Provincial Hospital of Traditional Chinese Medicine from 2002 to 2004. They were randomly assigned to two groups, the treatment group and the control group. Patients in the treatment group were administered with ELC before operation and after operation (starting from the 7th day post-operation), each for 3 months, while patients in the control group were untreated before operation and administered with Danazol from the 7th day post-operation for 3 months. Specimens of eutopic and ectopic endometrium in all patients of both groups were taken during the operation for detecting expressions of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA by polymerase chain reaction (PCR), and the incidence of post-operation recurrence was observed 12 months later. RESULTS: The 12-month follow-up showed that recurrence presented in 1 patient in the treatment group (3.3%), and 6 in the control group (20.0%), showing significant difference between them (P<0.05). The expressions of TIMP-1 mRNA in eutopic and ectopic endometrium were 0.85 +/- 0.36 and 0.76 +/- 0.57 in the treatment group, and 0.71 +/- 0.33 and 0.56 +/- 0.39 in the control group, while the expressions of MMP-9 mRNA were 0.36 +/- 0.40 and 0.35 +/- 0.35 vs 0.36 +/- 0.33 and 0.72 +/- 0.59, respectively. The expression of endometrial TIMP-1 mRNA, either eutopic or ectopic, was significantly higher, and the expression of ectopic endometrial MMP-9 mRNA was lower in the treatment group than that in the control group (P<0.01). CONCLUSION: ELC can reduce the invasive ability of endometrium tissue probably by regulating the balance of MMP/TIMP, namely, increase the expression of eutopic and ectopic endometrial TIMP-1 and decrease the expression of ectopic endometrial MMP-9, and thus to achieve its preventive and therapeutic effect on recurrence of OEC.

The effect of oral contraceptives on assisted reproductive technology [corrected] cycles.

PURPOSE OF REVIEW: To summarize the available data regarding the value of oral contraceptive pill addition in ovarian stimulation schemes used for in-vitro fertilization. RECENT FINDINGS: In agonists cycles, a decreased incidence of ovarian cyst formation is expected in patients pretreated with the oral contraceptive pill after gonadotropin-releasing hormone agonist administration compared to those treated according to a long follicular protocol. In antagonist cycles, oral contraceptive pill pretreatment appears to be feasible and has been used for programming cycle initiation. Solid evidence regarding its effect on the probability of pregnancy is, however, currently lacking. SUMMARY: The optimal use of oral contraceptive pretreatment as well as its effect on in-vitro fertilization outcome have not yet been fully explored. The effect of oral contraceptive pill pretreatment is worth further investigation in properly designed trials.

Formation of follicular cysts in cattle and therapeutic effects of controlled internal drug release.

Follicular cysts in cattle result from excessive growth of the dominant follicle without ovulation and still constitute a major reproductive disorder in this species. One key hormonal characteristic of cows with follicular cysts is the lack of an LH surge, although they have increased plasma estradiol concentrations. Another is a relatively high level of pulsatile secretion of LH that promotes continued growth of the dominant follicle. These LH characteristics seem to result from a functional abnormality in the feedback regulation of LH secretion by estradiol. Treatment with controlled internal drug release devices that increase circulating progesterone levels is effective in resolving follicular cystic conditions by 1) lowering pulsatile LH secretion and 2) restoring the ability of the hypothalamo-pituitary axis to generate an LH surge in response to an increase in circulating estradiol.

Functional ovarian cysts in premenopausal and gynecologically healthy women.

The present study describes 29 women coincidentally found to have ovarian cysts while participating in a cross-sectional study. The prevalence of functional ovarian cysts is determined. In this study, 428 women, aged 14-45 years, were examined by transvaginal ultrasonography. The women were gynecologically healthy and were using either no contraception, intrauterine contraceptive devices, none of which were hormone releasing, or oral contraception (OC). Cysts were defined as cystic spaces larger than 30 mm. All women were asymptomatic and regularly menstruating.The prevalence of ovarian cysts was lower for women using OC than for women using no contraception or using intrauterine contraceptive devices. The relative risk (measured as the prevalence proportion ratio) of having an ovarian cyst when using OC was 0.22 (CI: 0.13-0.39), compared to women not using OC. No difference was found in the prevalence of ovarian cysts between women using intrauterine contraceptive devices and women using no contraception. The prevalence of ovarian cyst increased throughout the menstrual cycle in women not using OC. This relation was not found in the group of users of OC. The majority of the cysts resolved within the first few days of menstruation. Sixty-five percent of the cysts persisting after menstruation had resolved at the first control examination 3 months later, independently of use of OC. Low-dose monophasic contraceptive pills seem to have a protective effect against development of functional ovarian cysts, independent of the type of gestagen and the dose of ethinylestradiol used. Ovarian cysts resolved independently of treatment with OC. The use of intrauterine contraceptive device had no influence on the occurrence of functional ovarian cysts.

Noncontraceptive benefits and therapeutic uses of the oral contraceptive pill.

The oral contraceptive pill is one of the most extensively studied medications ever prescribed. The health benefits are numerous and outweigh the risks of their use. Definitive evidence exists for protection against ovarian and endometrial cancers, benign breast disease, pelvic inflammatory disease requiring hospitalization, ectopic pregnancy, and iron-deficiency anemia. It has also been suggested that oral contraceptives may provide a benefit on bone mineral density, uterine fibroids, toxic shock syndrome, and colorectal cancer. Minimal supportive evidence exists for oral contraceptives protecting against the development of functional ovarian cysts and rheumatoid arthritis. Treatment of medical disorders with oral contraceptives is an "off-label" practice. Dysmenorrhea, irregular or excessive bleeding, acne, hirsutism, and endometriosis-associated pain are common targets for oral contraceptive therapy. Most patients are unaware of these health benefits and therapeutic uses of oral contraceptives, and they tend to overestimate their risk. Counseling and education are necessary to help women make well-informed health-care decisions and improve compliance.

Ovarian and endometrial function during hormonal contraception.

This report addresses the balance of benefits and risks from changes in ovarian and endometrial function from hormonal contraception. The main mode of action of hormonal contraception is inhibition of ovulation, due chiefly to the dose of oestrogen in combined oral contraceptives. With 20 microg dosages of ethinyl oestradiol follicular activity is more common so that contraception depends on suppression of the LH surge or disruption of the endometrial cycle. In polycystic ovary syndrome (PCOS) treated with oral contraceptives, cysts become smaller and in time the ovarian volume is reduced, ovarian testosterone secretion is reduced and there are potentially favourable effects on carbohydrate and lipid metabolism. Typical oral contraceptive users in the 1980s had a lower incidence of ovarian cysts, but modern oral contraceptives do not appear to affect the incidence of functional cysts or benign epithelial cysts. Moreover, randomized controlled trials indicate that oral contraception prescriptions are unlikely to prevent the development of functional cysts or to hasten their disappearance. Oral contraceptives, however, greatly reduce pelvic pain in women with symptomatic endometriosis and improve the health-related quality of life. Bleeding is a common response with all types of hormonal contraception, but current methodology is inadequate to make accurate comparisons of different products or of different phasic formulations. With continuing use, however, combined oral contraception is associated with endometrial atrophy, the biological plausibility for a reduced risk of endometrial carcinoma. With progestin-only contraception, a number of endometrial changes are considered as possible mechanisms of the associated bleeding but it remains largely unexplained. Oral contraceptives are frequently used for treatment of dysfunctional uterine bleeding, although only one trial has been reported. Oral contraceptive use confers protection from endometrial [relative risk (RR) 0.5] and ovarian (RR 0.4) cancers and in both cases, the protection lasts for up to 2 decades after stopping use.

Oral contraceptives: current status.

During the past four decades, oral contraceptives have remained a safe and effective method of birth control. Reductions in the estrogen and progestin dosages have significantly decreased the incidence of cardiovascular complications. The association between oral contraceptives and breast cancer appears to be primarily because of detection bias or possibly a promotional effect. Despite the changes in formulation, the problems related to side effects have not been totally solved. Because compliance and successful use is strongly affected by side effects, improvement in this area is probably the biggest challenge faced by developers of oral contraceptives. It is also clear that there are a growing number of significant noncontraceptive benefits that accrue in oral contraceptive users. Unfortunately, many women do not know about these benefits. Thus, one of the issues that providers need to continue to address is how to provide better information about oral contraceptives and contraception in general to patients.

Progestogen therapy during pituitary desensitization with gonadotropin-releasing hormone agonist prevents functional ovarian cyst formation: a prospective, randomized study.

OBJECTIVES: We sought to assess whether the use of norethindrone and gonadotropin-releasing hormone agonist therapy in the early follicular phase reduces the occurrence of functional ovarian cysts and shortens the duration of pituitary desensitization. We also assessed whether the use of norethindrone impairs implantation rates after in vitro fertilization treatment. STUDY DESIGN: We performed a prospective, randomized, single-blind study involving 117 patients who were randomized to receive norethindrone 24 hours before gonadotropin-releasing hormone agonist therapy (n = 63, treatment group) or gonadotropin-releasing hormone agonist alone (n = 54, control group) for pituitary desensitization. RESULTS: The incidence of functional ovarian cyst formation after 1 week of gonadotropin-releasing hormone agonist therapy was significantly lower in the treatment group compared with the control group. Furthermore, the duration of pituitary suppression was significantly shorter in the treatment group than in the control group. There were no significant differences between the 2 groups in the follicular response and embryo quality. Adjusted for age, the implantation rate (22% vs 9%, P =.02) and clinical pregnancy rate (34% vs 18%, P =.04) were significantly higher in the treatment group than in the control group. CONCLUSION: A combination of norethindrone and gonadotropin-releasing hormone agonist therapy is therefore more effective in achieving prompt pituitary suppression and should be considered for routine use during in vitro fertilization cycles.

Follow up of women with simple ovarian cysts detected by transvaginal sonography in the Tokyo metropolitan area.

OBJECTIVE: To investigate the management of women with asymptomatic ovarian masses, to determine the appropriate duration of follow up, and to identify diagnostic indicators of growing cysts. DESIGN: Review of women's hospital records. SETTING: Tokyo Metropolitan Cancer Detection Center, Japan. POPULATION: Two hundred and twenty-five pre- and postmenopausal women with a diagnosis of ovarian cyst < 6 cm in diameter and normal serum level of CA125, diagnosed between 1 October 1990 and 25 December 1991. MAIN OUTCOME MEASURE: Change in size of cyst as shown by ultrasound. RESULTS: Seventy-five months after initial diagnosis, 29 (13%) of the masses had progressed, 31 (14%) had persisted, and 165 (73%) had regressed. One hundred and nine masses (48%) had regressed within six months of the initial diagnosis. In univariate analysis transvaginal ultrasonographic assessment of morphology findings, cyst diameter, carcinoembyronic antigen (CEA) and CA19-9 were associated with the prognosis of the cyst. Multivariate regression analysis demonstrated that only the initial serum CA19-9 level and serum CEA level were significant predictors of ovarian masses that regressed (P for trend = 0.004 and 0.02, respectively). CONCLUSION: Simple ovarian cysts in patients with a normal level of CA125 have a low risk for ovarian cancer. Vaginal ultrasound at six months will identify regression of most simple cysts. CA19-9 and CEA at the initial diagnosis are useful parameters to predict future regression of ovarian cysts.