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On 19 July, 2024, at the age of almost 105 years, Joseph W. Goldzieher, the last survivor of the group of pioneers who created oral contraception, peacefully passed away. Here we briefly reconstruct the salient points in his long, productive life, and highlight his achievements in the development of hormonal contraception. His work is indissolubly enshrined in the complex history of hormonal contraception, from the first, fundamental observations, to the first clinical trials, both in the form of combined oestrogen-progestin oral pills and long-acting injectable contraceptives. After Pincus and his Group created an oral contraceptive containing an oestrogen and a progestin, Goldzieher was the second international scientist to conduct clinical trials of the new modality. He teamed-up with investigators in Mexico creating a fruitful, long-lasting collaboration. They produced evidence that ovulation inhibition could be achieved with all the progestins used at the time. Of importance, he was among the first to explore the possibility of using oestrogens to block ovulation, and developed the concept of sequential contraception. For all this lifetime of work, we believe he deserves to be named a 'giant in reproductive endocrinology'. [ABSTRACT FROM AUTHOR]

Progestin-only pills (POPs) have emerged as a crucial contraceptive option for women, particularly those contraindicated to oestrogens. This opinion paper introduces two new indices, the Inhibition Ratio (I.R.) (cyclical and daily) and the Transformation Index (T.I.), to evaluate and compare the efficacy and clinical behaviour of modern POPs. The I.R. quantifies the ratio between the progestin dosage in a POP and the minimum dose required to inhibit ovarian function, providing insights into contraceptive efficacy. The T.I., on the other hand, assesses its clinical impact by considering the ratio between the total progestin dose and the dose required to induce endometrial luteinising changes. Both indices thus offer valuable tools for comparing progestins even at significantly different dosages and regimens, providing information on clinical characteristics and drug effects. The newest formulations of POPs (Desogestrel 28 and Drospirenone 24 + 4) have demonstrated higher I.R. and T.I. in comparison to older versions, indicating significant improvements in contraceptive efficacy and clinical impact with better menstrual cycle control. We believe that using these indices will ensure a more informed and personalised choice of progestin not only for contraceptive purposes but also for therapeutic use in gynaecology. The future goal is to develop other progestins with even more advantageous I.R. and T.I., ensuring the best contraceptive efficacy with fewer side effects, even in women at risk (obese, etc.). SHORT CONDENSATION: The Inhibition Ratio (I.R.) (cyclical and daily) and the Transformation Index (T.I.) are two new proposed indexes to evaluate and compare the efficacy and clinical behaviour of modern and future POPs. [ABSTRACT FROM AUTHOR]

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 progestinonly 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. [ABSTRACT FROM AUTHOR]

Progestins used in contraception are either components of combined hormonal contraceptives or are used as a single active ingredient. Progestins are highly effective in long-term contraception and have a very good safety profile with very few contraindications. An oestrogen-free ovulation inhibitor POP has been authorised in the USA and the EU. It contains 4 mg of drospirenone (DRSP). The hormone administration regimen of 24 days followed by a 4-day hormone-free period was chosen to improve bleeding control and to maintain oestradiol concentrations at early follicular- phase levels, preventing oestrogen deficiency. Clinical trials have demonstrated high contraceptive effectiveness, a very low risk of cardiovascular risk events and a favourable bleeding pattern. Due to the long half-life of DRSP (30–34 h), the effectiveness is maintained even in case of a forgotten pill on a single occasion. Studies involving deliberate 4 days in one cycle 24-hour delays in taking a pill have demonstrated that ovulation inhibition is maintained if a single pill is missed. This review article will describe the clinical impact in the daily use of the 4 mg DRSP only pill and the resulting data on the effectiveness and safety of this hormonal contraceptive. The 4 mg drospirenone-only pill improves the bleeding profile in comparison to 0.075 mg desogestrel and achieves high contraceptive efficacy even with a 24 h missed pill window. [ABSTRACT FROM AUTHOR]

Purpose: Despite considerable advances in recently developed combined oral contraceptives (COCs), resulting in lower rates of adverse events while maintaining contraceptive efficacy, there is interest in further innovation.Materials and Methods: Estetrol (E4), a native oestrogen, and progestin drospirenone (DRSP) were combined in a new COC. A European expert panel reviewed the pharmacology, efficacy, and safety and tolerability of this combination. Their findings are presented as a narrative review.Results: E4 15 mg/DRSP 3 mg in a 24/4 regimen provided effective contraception with good cycle control, characterised by a predictable regular bleeding pattern and minimal unscheduled bleeding, together with a good safety profile. The combination was associated with high user satisfaction, well-being, and minimal changes in body weight. The effects on endocrine and metabolic parameters were limited, and the combination was found to have a limited impact on liver function and lipid and carbohydrate metabolism. Moreover, its effect on several haemostatic parameters was lower than that of comparators containing ethinyl oestradiol (EE) 20 µg/DRSP 3 mg and EE 30 µg/levonorgestrel 150 µg.Conclusion: E4 15 mg/DRSP 3 mg provides safe and effective contraception, with high user satisfaction and predictable bleeding. Further research will evaluate the long-term safety of the COC. [ABSTRACT FROM AUTHOR]

Objective: Adolescents with anorexia nervosa (AN) are at increased risk of unplanned pregnancies and bone loss, due to low oestrogen levels and low use of efficient contraception. The negative impact of combined hormonal contraceptives (CHC) on peak bone mass during adolescence might limit wider use in anorexic women. Another issue limiting CHC use is the concern, that CHC-induced cyclic bleeding reduces the motivation for further weight gain and thus exerts a negative impact on recovery. We wanted to find evidence based answers about the impact of CHC use on bone health and course of the disease in adolescents with AN.Methods: We performed a narrative review of the current literature investigating the effect of CHC or progestin-only contraceptives on bone density, body shape and course of disease in young women with anorexia.Results: There is no evidence that CHC use aggravates the bone loss associated with AN. In long-term users CHC exert a protective effect. Anorexic women using CHC showed at least the same or a greater weight gain in comparison with controls. Eating disorder attitudes did not worsen.Conclusion: We conclude, that at present there is no evidence, that use of CHC by AN patients has a negative impact on bone density or the course of disease. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the study was to update the results of a previous study published 10 years ago and compare the effect on hyperandrogenism of a newer progestin, dienogest (DNG), in a combined oral contraceptive (COC) formulation with ethinylestradiol (EE), with that of COCs containing the same dose of EE in combination with drospirenone (DRSP) and chlormadinone acetate (CMA).Methods: Sixty women with polycystic ovary syndrome (PCOS) aged between 16 and 35 and requiring antiandrogenic contraceptive treatment were randomised to one of three treatment groups: EE 30 µg/DRSP 3 mg, EE 30 µg/CMA 2 mg, EE 30 µg/DNG 2 mg. We evaluated the effects of the three COCs on sex hormone-binding globulin (SHBG) and biochemical markers of hyperandrogenism.Results: After 3 months of treatment, serum androgen concentrations were significantly improved in all treatment groups. Serum concentrations of SHBG were significantly increased with all COC treatments (p < 0.0001). Interestingly, DRSP had a greater effect (+218%; p < 0.0001) on serum SHBG concentrations compared with DNG and CMA (p < 0.04 and p < 0.002, respectively). Serum concentrations of total testosterone significantly decreased in all groups (p < 0.0001). DRSP had a significantly greater effect on total testosterone concentrations compared with DNG (p = 0.002) and CMA (p < 0.0001).Conclusion: Our study showed that DNG exerted an important stimulatory effect on SHBG concentrations, which was less than that of DRSP but greater than that of CMA. Similar results were also obtained for dehydroepiandrosterone sulphate and total testosterone. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the study was to assess whether the ovarian reserve markers anti-Müllerian hormone (AMH) and antral follicle count (AFC) were lower among women using the progestin-only pill (POP) or levonorgestrel-releasing intrauterine system (LNG-IUS) and similar to the decrease observed in combined oral contraceptive (COC) pill users.Methods: This retrospective study comprised 565 hormonal contraceptive users (COC, POP, LNG-IUS or contraceptive vaginal ring) and 983 non-hormonal contraceptive users, who were seen in two Danish fertility assessment and counselling clinics between 2015 and 2019. Adjusted multiple regression analysis was used to examine the differences in AMH and AFC between hormonal and non-hormonal contraceptive users.Results: Compared with non-hormonal contraceptive users, AMH was 31.1% lower among COC users [95% confidence interval (CI) -39.6%, -25.9%; p < 0.001], 35.6% lower among POP users (95% CI -49.0%, -18.6%; p < 0.001) and 17.1% lower among LNG-IUS users (95% CI -31.4%, 0.002%; p = 0.052); no significant differences were seen among vaginal ring users. Compared with non-hormonal contraceptive users, AFC was 31.3% lower among COC users (95% CI -35.0%, -25.3%; p < 0.001) and 29.7% lower among POP users (-39.1%, -17.9%; p < 0.001); no significant differences were seen among LNG-IUS or vaginal ring users. Ovarian volume was more than 50% reduced among COC and vaginal ring users (p < 0.001) but was unchanged among POP and LNG-IUS users.Conclusion: Assessment of ovarian reserve markers among users of all types of hormonal contraception should be interpreted cautiously and the type of contraceptive method considered. [ABSTRACT FROM AUTHOR]

Purpose: Prior studies evaluating the effect of administered progestogens on peak cervical mucus have not controlled for the influence of endogenous hormones. To address this, we treated women with a gonadotropin-releasing hormone (GnRH) agonist to suppress the hypothalamus-pituitary-ovarian (HPO) axis and used transdermal oestradiol replacement to stimulate peak cervical mucus and then evaluated the effects of an oral progestin or oestradiol withdrawal. Materials and methods: We used a crossover design to examine cervical mucus changes in women receiving transdermal oestradiol replacement following intramuscular administration of leuprolide acetate. After increasing oestradiol patches to mid-cycle levels, subjects were assigned to either 0.35 mg oral norethindrone with continuation of the patches (NET) or oestradiol withdrawal by patch removal (E2WD). We collected serum and cervical mucus samples at 0, 2, 4, 6, 22 and 24 h following the intervention. Results: We analysed 12 cycles (6 NET, 6 E2WD) from three subjects. Baseline cervical mucus scores were favourable to sperm penetration [NET median 11, interquartile range (9-12), E2WD 13 (12-13)]. Two hours after removal of oestradiol patch or administration of norethindrone, cervical mucus scores declined [NET 8.5 (4-9), E2WD 10.5 (10-12)]. Low cervical mucus scores persisted at 24 h with NET [8.0 (7-8)] but not E2WD [10.5 (8-11)]. Conclusions: We observed a rapid decline in cervical mucus Insler scores following administration of a single dose of oral norethindrone, and scores remained lower and unfavourable through 24 h. Oestradiol withdrawal did not result in similar unfavourable changes. [ABSTRACT FROM AUTHOR]

Introduction: Lack of awareness of reproductive hormone-related mood changes in the general population or limited acknowledgement of their existence by health care providers regularly contribute to fears or misconceptions about the link between hormonal contraception and potential mood changes. Recent media discussion linked the levonorgestrel intrauterine system (LNG-IUS 20 µg/d) to elevated cortisol levels and the possibility of panic attacks, anxiety, mood changes, sleep disturbance and restlessness. Efficacy of the LNG-IUS is based primarily on local effects but systemic effects, including a potential increase in mood symptoms, are a known risk and reflected in the product labelling for all LNG-IUS products.Objective: There is a need to improve communication to the public and health care providers around potential risk of mood disorders in order to facilitate 'informed choice' amongst women considering an LNG-IUS as their contraceptive method and directly address the fears of women currently using an LNG-IUS.Results: We propose a simple and brief, step-by-step process that can be embedded within current counselling that explores and clarifies the potential risk of developing mood symptoms prior to placement of LNG-IUS. It also addresses concerns from women using an LNG-IUS who either present with mood symptoms or are concerned about potential onset.Conclusion: Mood symptoms with use of LNG-IUS are uncommon; however, all women, including those who may experience an increased sensitivity to certain progestins, should be counselled appropriately to raise awareness of the potential risk within an informed discussion around effectiveness, benefits and possible adverse events. [ABSTRACT FROM AUTHOR]

Purpose: To identify at least one contraceptive vaginal ring that effectively inhibits ovulation and demonstrates cycle control that is non-inferior to NuvaRing® (Merck Sharp & Dohme B.V., The Netherlands) in terms of an unscheduled bleeding incidence, with a non-inferiority margin of 10%.Methods: This was a randomised, active controlled, parallel group, multicentre, partially blinded trial in healthy women 18-35 years of age. Subjects received one of six contraceptive vaginal rings with an average daily release rate of 300 µg 17β-estradiol (E2) and various rates of either etonogestrel (ENG; 75, 100, or 125 µg/day) or nomegestrol acetate (NOMAC; 500, 700, or 900 µg/day), or the active control NuvaRing® (ENG/ethinylestradiol 120/15 µg), for three 28-day cycles.Results: Ovulation inhibition was observed in all groups as confirmed by absence of progesterone concentrations compatible with ovulation (>16 nmol/L) and absence of ultrasound evidence of ovulation. All investigational rings provided good cycle control, with the ENG-E2 125/300 µg/day group being associated with the best cycle control based on the numerically lowest incidence of unscheduled bleeding and absence of scheduled bleeding. Non-inferiority to NuvaRing® with respect to the incidence of unscheduled bleeding could not be concluded for any of the investigational ring groups. The safety profile was consistent with the known safety profile of combined estrogen/progestin contraceptives and similar across all groups.Conclusions: Contraceptive rings releasing 300 µg E2 and 75-125 µg/day of ENG or 500-900 µg/day of NOMAC provided adequate ovulation inhibition and cycle control and are generally well-tolerated. While non-inferiority to NuvaRing® was not met, among the investigational rings, the ENG-E2 125/300 ring provided the best cycle control. [ABSTRACT FROM AUTHOR]

Purpose: Timing of sample collection represents a major source of variability in studies evaluating the effects of administered agents on cervical mucus in naturally-cycling women. We sought to create and validate an artificial model of the cervical mucus cycle using exogenous E2 and P4 replacement in ovarian suppressed women.Materials and Methods: We conducted a prospective experiment (clinicaltrials.gov, NCT02969590) examining cervical mucus changes in six women during natural and artificial menstrual cycles [leuprolide acetate, estradiol transdermal patch (0.05-0.3 mg/day) and progesterone 200 mg/day]. We collected serum and mucus samples at each visit corresponding to early, mid and late follicular, ovulation and mid-luteal time points in the natural and artificial cycles. We evaluated mucus according to the modified Insler score described in the WHO laboratory Manual for the Examination and Processing of Human Semen.Results: We enrolled healthy women between 27 and 40 years of age. All of the subjects achieved a mucus score of ≥10 both in the natural cycle and during peak estradiol replacement levels (0.3 mg/day) in the artificial cycle. During the simulated luteal phase, all mucus scores were ≤5 (median 3.5; range 1-5), similar to scores seen in the luteal phase of natural cycles (median 1; range 1-3).Conclusions: Our artificial cycle model (leuprolide acetate suppression) and dose escalation with estradiol patches produced favourable cervical mucus with mucus scores similar to those in the periovulatory phase of natural menstrual cycles. Additional studies are needed to validate the model for evaluation of mucus effects of contraceptive agents. [ABSTRACT FROM AUTHOR]

Introduction: Abortion is often a difficult and traumatic decision for a woman to make. Perhaps greater distress occurs when a woman commences a medical abortion but then changes her mind and wishes to keep the now-threatened pregnancy. One published case series detailed a potential method to counter/reverse the abortifacient effect of mifepristone by administering parenteral progesterone in such situations.Objectives: The present report details cases of women in similar circumstances who have been treated with progesterone. The aims were to document occurrences of where women have changed their mind after commencing medical abortion, as well as to explore some of the controversies and clinical issues surrounding their circumstances.Methods: Women who had commenced medical abortion by ingesting mifepristone but who had not taken misoprostol independently contacted a national pregnancy support service the same day. Those meeting criteria for treatment received progesterone pessaries per vaginum for two weeks.Results: Cases: 28-year-old woman, 6 weeks plus 1 day gestation; 35-year-old woman, 8 weeks plus 5 days gestation; and 27-year-old woman, 7 weeks plus 3 days gestation. Outcomes respectively were: healthy male baby delivered at 39 weeks gestation; healthy male baby delivered at term; and completed medical abortion.Conclusions: Women have changed their mind after commencing medical abortion. Progesterone use in early pregnancy is low risk and its application to counter the effects of mifepristone in such circumstances may be clinically beneficial in preserving her threatened pregnancy. Further research is required, however, to provide definitive evidence. [ABSTRACT FROM AUTHOR]

Purpose: The progestogen-only intramuscular injectable Depo-Provera® (depot medroxyprogesterone acetate) is an effective contraceptive method, but users need to attend a clinic every 12-13 weeks for a repeat injection from a doctor/nurse. This limits convenience of the method and may affect continuation rates. We conducted a pilot study to examine the feasibility and acceptability of users receiving the subcutaneous form of the contraception injection from pharmacists in the community pharmacy setting.Materials and Methods: Existing users of Depo-Provera®, who wished to switch to the subcutaneous preparation with the same active ingredient (Sayana Press®) were invited to attend 1 of 11 community pharmacies for up to three repeat injections, given by a pharmacist. Evaluation consisted of (i) self-administered questionnaires of women and (ii) interviews with participating pharmacists, at study exit on their respective experiences.Results: Global unavailability of the product during the study adversely affected recruitment and retention. 50 women were recruited. Only 48 injections were delivered at the pharmacy out of a possible 150 (34%). About 26 participants received no injections at the pharmacy and only seven (14%) participants received all three injections at the pharmacy. Participants reported mixed experiences, with some welcoming the intervention but others experiencing difficulty with pharmacist availability. Pharmacists were enthusiastic about this expansion of their role, and did not view their availability as a barrier to service delivery.Conclusions: Delivery of the subcutaneous contraceptive injectable from a community pharmacy may be feasible but availability of sufficient numbers of pharmacists trained in this technique is necessary for a robust model of service delivery. [ABSTRACT FROM AUTHOR]

Objectives: To estimate the real-use contraceptive effectiveness of the combined oral contraceptive containing dienogest and estradiol valerate (DNG/EV) and whether DNG/EV compared to other combined oral contraceptives (oCOC) has a negative effect on return to fertility.Methods: Transatlantic, prospective, non-interventional cohort study conducted in the USA and seven European countries with two main exposure groups and one exposure subgroup: new users of DNG/EV and other COC (oCOC), particularly levonorgestrel-containing COCs (LNG). In a planned secondary analysis, pregnancy outcomes were investigated including contraceptive effectiveness and pregnancy following contraceptive cessation. The influence of age, parity and OC-type were assessed.Results: 50,203 COC users were followed for 105,761 woman-years (WY). There were 677 unintended pregnancies reported: 451 in the USA and 226 in Europe. The contraceptive failure rate in Europe was 0.5 events/100 WY (95% CI: 0.4-0.5) and in the USA 1.9 events/100 WY (95% CI: 1.7-2.1). Differences in compliance (1.3 pregnancies/100 WY) accounted for 90% of the geographical difference seen between Europe and the USA. DNG/EV showed lower contraceptive failure rates compared to the comparators; 0.9% DNG/EV, 2.1% oCOC and 2.8% LNG after 4 years. Overall, 1167 (2.3%) of women stopped contraceptive use with the intention of becoming pregnant with 89% conceiving within 2 years. No significant differences were seen between groups after adjusting for age.Conclusion/discussion: DNG/EV is associated with similar contraceptive effectiveness in typical-use settings when compared to oCOC and LNG. There was no difference observed between cohorts in fertility following OC use. [ABSTRACT FROM AUTHOR]

Objectives: Adverse mood changes are sometimes cited as a reason for discontinuing combined hormonal contraception (CHC). A systematic review of recent literature was undertaken to characterise the nature of these side effects and identify characteristics that might predispose women to such effects.Methods: A MEDLINE review of studies from the past 30 years that focused on CHC and mood was performed. Database search was supplemented with studies found through citations and references.Results: The research literature on this topic is limited by a lack of prospective studies, a variety of measurements of mood, and a consolidation of many disparate types of contraceptives studied together in a single cohort. Common themes that emerge from review of these papers include (1) most women using CHC demonstrate no effect or a beneficial effect on mood, with a low incidence of adverse effects; (2) contraceptives containing less androgenic progestins may have fewer adverse effects on mood; (3) continuous and perhaps non-oral dosing of CHC has the fewest mood effects; (4) women with underlying mood disorders may be predisposed to mood effects, but this may reflect factors related to choice of contraception rather than the mood disorder itself.Conclusion: Inconsistent research methods and lack of uniform assessments make it difficult to make strong conclusions about which CHC users are at risk for adverse mood effects. Until more prospective data is available, clinicians should recognise that such effects are infrequent and CHC may be prescribed with confidence. [ABSTRACT FROM AUTHOR]

Objectives: The study investigated the effects on female sexual function of a progestogen-containing combined oral contraceptives (COCs) with an antiandrogenic profile taken in a continuous regimen.Methods: In this prospective randomised single-institution study, 80 healthy women with a monogamous partner and an active sexual life were randomised into two groups for a period of 3 months. Women in the exposed group (n = 40) took a COCs containing 30 μg ethinylestradiol (EE) and 3 mg drospirenone (DRSP) in a 21/7 regimen. Women in the control group (n = 40) used either a barrier contraceptive method (BCM) or a natural family planning method (NFPM). Participants were asked to complete a set of validated questionnaires to assess sociodemographic variables and measure Female Sexual Function Index (FSFI).Results: The total FSFI score (p < 0.0001), as well as the desire (p = 0.04) and arousal (p = 0.03) scores, were significantly lower in the COCs group after 3 months of hormonal contraceptive use compared with baseline. Women using BCM or NFPM showed an improvement in total FSFI score (p = 0.02). Hormonal contraception with DRSP increased the likelihood of worse sexual function in the desire (odds ratio [OR] 2.47; 95% confidence interval [CI] 1.22, 4.98; p = 0.01) and arousal domains (OR 2.85; 95%CI 1.34, 5.93; p = 0.005) and in total FSFI score (OR 2.01; 95%CI 1.45, 2.79; p < 0.001). The results remained statistically significant even after adjustment for smoking status.Conclusions: The study found evidence that women taking a combined EE/DRSP COCs for 3 months may have a worsening of sexual function as measured by FSFI. [ABSTRACT FROM AUTHOR]

Objective: The effect on body composition and in particular on fat mass (FM) of 12 months' use of a desogestrel (DSG)-only contraceptive pill or the levonorgestrel-releasing intrauterine system (LNG-IUS) was evaluated in women in the perimenopause.Methods: An observational study comprised 102 perimenopausal women: 42 received a 75 μg DSG pill, 34 received the 52 mg LNG-IUS, and 26 received no treatment. Body composition, body weight and resting metabolic rate (RMR) were evaluated at baseline and again after 12 months.Results: FM did not change in the control group (- 0.5 ± 1.6%) but significantly increased in the LNG-IUS group (+ 1.1 ± 2.9%; p = 0.02 vs. controls) and in the DSG group (+ 2.8 ± 3.5%; p = 0.0001 vs. controls; p = 0.02 vs. LNG-IUS). Women treated with DSG or the LNG-IUS showed a non-significant increase in body weight, body mass index and waist circumference. RMR did not significantly vary in the control group (- 3.8 ± 292.9 kJ/ 24 h) and tended to decrease but not significantly in the LNG-IUS (115.5 ± 531.8 kJ/ 24 h) and DSG groups (305.9 ± 556.9 kJ/24 h).Conclusions: The results of this preliminary study seem to indicate that in perimenopausal women continuous use of the DSG-only pill and to a lesser extent the LNG-IUS may favour FM accumulation. [ABSTRACT FROM AUTHOR]

ObjectiveSince its introduction 50 years ago, the contraceptive pill has continuously evolved to decrease the risk of venous thromboembolism (VTE) associated with its use. An increased risk of VTE still remains, however. Other concerns, such as effects on lipid and carbohydrate metabolism, have also been reported. In this study we compared two reference combined oral contraceptives (COCs) containing ethinylestradiol (EE)/levonorgestrel (LNG) and EE/drospirenone (DRSP) with COCs containing estradiol (E2) (estradiol valerate [E2V]/dienogest [DNG] and E2/nomegestrol acetate [NOMAC]). They were evaluated according to their influence on recognised haemostatic and metabolic markers. MethodsA literature search of the MEDLINE/PubMed database was conducted for head-to-head studies. EE/LNG was chosen as the comparator pill. ResultsThe haemostatic impact of E2pills and EE/LNG has been extensively compared, in contrast to that of EE/DRSP and EE/LNG. Changes in haemostatic and metabolic marker levels between EE/LNG and E2V/DNG were generally not statistically significant. E2/NOMAC showed statistically significantly favourable results on haemostatic markers and had a neutral effect on carbohydrate and lipid metabolism when compared with EE/LNG. ConclusionE2/NOMAC exhibits less haemostatic and metabolic impact than EE/LNG and other COCs, suggesting that it may be a promising candidate to reduce residual VTE risk associated with COC use. Confirmation from a well-powered prospective clinical trial is, however, needed. Chinese Abstract 摘要 目的自50年前推出以来,口服避孕药不断降低与其使用相关的静脉血栓栓塞(VTE)的风险。但是，增加的静脉血栓栓塞风险仍然存在。其他担忧，如对脂质和碳水化合物代谢的影响也有报道。这项研究中，我们将含炔雌醇（EE）/左炔诺孕酮（LNG）和含炔雌醇/屈螺酮（DRSP）的2个参照复方口服避孕药(COCs)与含雌二醇（E2）（戊酸雌二醇[E2V] /地诺孕素[DNG]和雌二醇/醋酸诺美孕酮[NOMAC]）的复方口服避孕药进行比较。根据它们对已确定的止血和代谢指标的影响来评估。 方法使用MEDLINE/PubMed数据库文献检索进行头对头研究。选择炔雌醇/左炔诺孕酮作为对照组。 结果相比于炔雌醇/屈螺酮和炔雌醇/左炔诺孕酮的止血影响，雌二醇片和炔雌醇/左炔诺孕酮的止血影响被广泛比较。炔雌醇/左炔诺孕酮与戊酸雌二醇/地诺孕素之间的止血和代谢指标的变化则不具统计学意义。与炔雌醇/左炔诺孕酮相比，雌二醇/醋酸诺美孕酮对止血指标具有明显有利的结果，对碳水化合物和脂质代谢则是中性效应。 结论相比于含炔雌醇/左炔诺孕酮口服避孕药及其他口服避孕药，含雌二醇/醋酸诺美孕酮口服避孕药具有更少的止血和代谢影响，这表明它可能是降低与口服避孕药相关的静脉血栓栓塞风险的一种有希望的候选药品。然而，这仍需要良好的前瞻性临床试验来验证。 关键词 复合口服避孕药，雌二醇，炔雌醇，止血指标，脂质和碳水化合物代谢指标，孕激素，静脉血栓栓塞 [ABSTRACT FROM PUBLISHER]

Objective To compare cervical mucus score (CMS) with and without protease inhibitors (PI) before and after taking norethindrone (NET). Study design This two-arm, researcher blinded, non-randomised, prospective study was conducted to evaluate cervical mucus quality in HIV-positive women taking progestin only pills. The study group was taking a PI, and compared to women taking ARV regimens that have demonstrated no significant interaction with NET in prior pharmacokinetic trials with combined oral contraceptives. The women had a cervical mucus score prior to NET administration. Mucus Scoring was repeated after 21 days of steady state exposure to oral NET 0.35 milligrams. Cervical mucus quality was quantified according to the World Health Organisation criteria, which include: volume, consistency, cellularity, spinnbarkeit, and ferning. Results Sixteen women took PI and 17 were controls. Baseline CMS were similar ( p ≥ 0.1). After 21 days CMS were similar among the two groups ( p = 1). Conclusions HIV-positive women taking PI demonstrated thickened cervical mucus with oral norethindrone 0.35 mg and are similar to HIV-positive women taking no PI therapy. This may suggest no difference in contraceptive efficacy of progestin only pills in HIV-positive women taking PI. [ABSTRACT FROM AUTHOR]

Hormonal fluctuations during the natural cycle, as well as progestins used for hormonal contraception, can exert effects on mood especially in vulnerable women. Negative effects of levonorgestrel-releasing intrauterine contraception on mood are rare. [ABSTRACT FROM PUBLISHER]

Background Long-acting reversible contraceptive methods (LARCs) are safe, highly effective, readily reversible, and require no action on the part of the user following insertion. Early discontinuation may put women at increased risk of unintended pregnancy. Methods Following insertion of a progestogen-only subdermal implant or intrauterine system (IUS) at Family Planning NSW, women 18 years and older completed a questionnaire about their choice. At 6 weeks, 6, 12, 24 and 36 months by telephone or online they completed a questionnaire about bleeding patterns, side effects, satisfaction, and reasons for discontinuation. Results Two hundred IUS users and 149 implant users were enrolled. The former were generally older, married or in a de-facto relationship, and had children. Forty-seven percent of implant users discontinued within three years compared to 27% of IUS users ( p = 0.002). In the first two years amenorrhoea was more frequent in implant users. Frequent bleeding/spotting was more prevalent in the first year of IUS use but over time was twice as prevalent in implant users. Infrequent bleeding/spotting was more common in IUS users. Conclusion Both devices are highly effective and acceptable cost-effective methods. While LARCs should be promoted to women of all ages seeking contraception, early discontinuation due to unacceptable bleeding highlights the need for pre-insertion counselling. [ABSTRACT FROM AUTHOR]

Objectives To compare two-year continuation rates and user satisfaction with the levonorgestrel releasing-intrauterine system (LNG-IUS) and the etonogestrel releasing-subdermal implant (ENG implant) in women in Europe. Methods This prospective, non-interventional study was undertaken at 72 sites in France ( n = 61), Great Britain ( n = 2), Ireland ( n = 3) and Slovakia ( n = 6). Women opting to switch their method of contraception to the LNG-IUS or the ENG implant were followed-up over 24 months to document continuation and satisfaction with their chosen contraceptive method. Reasons for discontinuation were documented. Results The data analysed were based on 363 women (LNG-IUS [ n = 247] and ENG implant [ n = 116]), aged 20 to 45 years, with at least one follow-up visit after contraceptive placement. The documented cumulative continuation rate was 82% in the LNG-IUS group and 67% in the ENG implant group at 24 months. The documented discontinuation rates were 13% and 17%, respectively. Bleeding problems were cited as reason for discontinuation in 4% and 11% of women in the LNG-IUS and ENG implant groups, respectively. Conclusions The LNG-IUS is associated with higher continuation rates and user satisfaction than the ENG implant in this study of women in Europe, though the groups were not similar in all respects. Bleeding problems with the ENG implant account for most of the reasons for discontinuing its use. [ABSTRACT FROM AUTHOR]

The author offers a statement on the risk of thromboembolism posed by combined hormonal contraceptives that contain third- or fourth-generation progestogens or cyproterone acetate. Topics discussed include the cause of the pill scare, the objectives of contraception and the evidence concerning the risk of venous thromboembolism (VTE). Practical recommendations for women are also provided.

The authors address the safety and efficacy of oral contraceptives (OCs) among its users. Topics discussed include adverse events reports related to OC use, evidence about mortality from cohort studies, and the findings of the Royal College of General Practitioners' (RGCP) Oral Contraception Study in Great Britain.

Background and objectives It has been suggested that taking oral contraceptives (OCs) may increase breast cancer incidence. However, data in this regard are inconsistent. We performed this meta-analysis to estimate the association between OC use and breast cancer risk. Methods Prospective cohort studies on OC use and breast cancer risk were identified by searching databases from the period 1960 to 2012. Results from individual studies were synthetically combined using STATA 11 software. Results A total of 13 prospective cohort studies were included in our meta-analysis, involving 11,722 cases and 859,894 participants. The combined relative risk (RR) of breast cancer for ever- compared with never-OC users was 1.08 (95% confidence interval [CI]: 0.99-1.17). Dose-response analysis based on five eligible studies showed that every ten-years' increment of OC use was associated with a significant 14% (95% CI: 1.05-1.23) rise in breast cancer risk. Little evidence of publication bias was found. Conclusions This meta-analysis provides evidence of a non-significant increase in breast cancer risk associated with ever OC use, but the risk for long-term OC users is significantly greater. However, the latter finding is based on only a limited number of studies. [ABSTRACT FROM AUTHOR]

Objective To evaluate endometrial and ovarian effects, and bleeding patterns, among users of Depo-Provera®, Norplant®, and Implanon®. Study design One-hundred and fifty women, who had been using one of these long-acting progestin-only contraceptives (LAPCs) for at least the previous six months, with fifty in each of the groups, were assessed. Results All results are mentioned in the following sequence: (1) Depo-Provera®, (2) Norplant®, and (3) Implanon®. Normal bleeding was reported by 0%, 52%, and 8%; amenorrhoea or infrequent bleeding by 68%, 24%, and 72%; and abnormal bleeding by 32%, 24%, and 20%, respectively ( p < 0.001). Histological evaluation revealed an atrophic endometrium in 84%, 32%, and 28%, respectively ( p < 0.0001); a progestin effect in 16%, 28%, and 62%, respectively ( p < 0.0001), and a proliferative pattern in 0%, 40%, and 10%, respectively ( p < 0.0001). Endometrial thickness was 3 ± 0.41 mm, 3.62 ± 0.65 mm, and 5.2 ± 0.84 mm, respectively ( p < 0.0001). Follicular growth in the ovaries was observed at ultrasound in 12%, 40%, and 72%, respectively ( p < 0.001). Conclusion Bleeding patterns, endometrial thickness, ovarian activity, and endometrial histology among Egyptian users of LAPCs differed significantly depending on the nature of the contraceptive. [ABSTRACT FROM AUTHOR]

Objective To explore the optimal dose of the progestogen, nomegestrol acetate (NOMAC), required in a monophasic oral contraceptive, in combination with 1.5 mg 17 ββ-oestradiol (E2), to inhibit ovulation. Methods A double-blind, randomised study assessing 41 normally cycling women (aged 18--35 years) over two screening cycles, one control cycle and one consecutive treatment cycle; 38 women completed the treatment period. Subjects received 0.625 mg NOMAC/1.5 mg E2 ( n == 9), 1.25 mg NOMAC/1.5 mg E2 ( n == 10), 2.5 mg NOMAC/1.5 mg E2 ( n == 10) or 2.5 mg NOMAC alone ( n == 9) for 21 days. Results During the treatment cycle, ovulation was suppressed in all treatment groups. The lowest plasma E2 levels were observed with 2.5 mg NOMAC given alone. Addition of 1.5 mg E2 to 2.5 mg NOMAC resulted in statistically significant increases in E2 levels and decreases in mean follicle-stimulating hormone and luteinising hormone levels. In the three NOMAC/E2 combination groups, a statistically significant inverse correlation was found between E2 plasma levels and NOMAC dose. Conclusion The dose of 2.5 mg NOMAC was confirmed to be optimal to inhibit both ovulation and follicular maturation. The antigonadotropic effect of 2.5 mg NOMAC was reinforced when combined with 1.5 mg E2. [ABSTRACT FROM AUTHOR]

Objectives The relation between the use of different hormonal contraceptives and antidepressant therapy was investigated. Methods In a nationwide cross-sectional study among all women in Sweden aged 16–31, drug expenditure data on hormonal contraceptives and antidepressants were obtained from the Swedish Prescribed Drug Register. Odds ratios (ORs) for antidepressant use were calculated by logistic regression for progestin-only users versus non-users as well as for combined hormonal contraceptive (CHC) users versus non-users. Results In the study population ( N = 917,993), 58.9% were hormonal contraceptive users, and 8.5% were antidepressant users. The age-pattern for antidepressant ORs differed between the two types of users of contraceptives; progestin-only users had significant ORs above 1 in all age groups whereas among CHC users the OR was above 1 solely in those aged 16–19. The largest difference between types of users was seen in the age group 16–19 in which women resorting to a progestin-only contraceptive had a 67% (95% confidence interval: 57– 78%) higher antidepressant use than women treated with a CHC. Conclusion Progestin-only contraceptive users resorted to antidepressants more than users of CHCs. This phenomenon is particularly pronounced among teenagers. Therefore, special attention should be given to young women's mental history when prescribing hormonal contraceptives and vice versa: the contraceptive history should be taken into account when prescribing antidepressants. [ABSTRACT FROM AUTHOR]

Objectives To prospectively investigate if women with multiple sclerosis (MS) experience changes in MS-symptoms in relation to cyclical hormonal changes. Methods Sixty-three women with MS, either with regular, spontaneous menstrual cycles or taking combined oral contraceptives (COCs), were asked to score their MS symptoms every day during three cycles. Symptom scores were analysed in relation to different phases of the spontaneous menstrual- or pill-driven cycle. Results Twenty-three women completed the score record. Among the 16 women who were not using a COC there were no significant differences in symptom scores between the phases of the menstrual cycle. The seven women taking a COC reported significantly higher symptom score points for weakness, numbness and tiredness during the pill-free interval compared with the phase during which they took the COC daily. Conclusions This prospective study appears to contradict earlier retrospective studies regarding variations in MS symptoms in relation to the menstrual cycle in women who are not using a COC. The lower symptom scores during the three weeks of pill taking suggest a positive effect of the steroids on the manifestations of MS. Further studies concerning both short- and long-term effects of OC-use on MS symptoms are needed. [ABSTRACT FROM AUTHOR]

Objective To evaluate the pharmacokinetics of a combined oral contraceptive (OC) containing oestradiol valerate/dienogest (E2V/DNG) administered according to a four-phasic dosing regimen with an oestrogen step-down and a progestin step-up over 26 days of active treatment. Methods This Phase I, open-label study included healthy women aged 18-50 years. Treatment consisted of the administration of E2V 3 mg for 2 days, E2V 2 mg/DNG 2 mg for 5 days, E2V 2 mg/DNG 3 mg for 17 days, E2V 1 mg for 2 days, and placebo for 2 days. Results Pharmacokinetic data were analysed in 15 women. Stable E2 concentrations were maintained throughout the study. Minimum mean serum E2 levels were 33.6-64.7 pg/ml during E2V administration. The ratio of oestrone:E2 in serum was approximately 5:1. Minimum mean serum DNG levels were 6.8-15.1 ng/ml during DNG administration. Minimum concentrations of DNG increased only slightly during each phase of the regimen during which DNG was being administered. On day 24 the geometric mean Cmax, Cave and t½ of DNG were 82.9 ng/ml, 33.7 ng/ml and 12.2 hours, respectively; the median tmax was 1.5 hours. Serum sex hormone-binding globulin concentrations increased by 40% (within the normal range). Cortisol binding-globulin levels remained almost unchanged. Treatment was well tolerated. Conclusions Treatment with an OC containing E2V and DNG was well tolerated and was associated with stable E2 concentrations over 28 days. The pharmacokinetics of DNG were consistent with previous findings. Minimum serum concentrations of DNG increased only slightly during phases of the regimen during which DNG was administered. [ABSTRACT FROM AUTHOR]

New options for hormonal replacement therapy (HRT) include non-oral, low-dose sustained delivery of progestins in different formulations. Since the Women's Health Initiative (WHI) study, prescription trends were observed selecting progesterone over other progestins, or delivering the progestin parenterally, in order to reach low systemic levels of the steroid. Such modalities include progesterone vaginal rings or gels, and intra-uterine systems (IUSs). When given via the transdermal and intranasal routes, the hormones are delivered systemically although the first liver impact is by-passed. Of the progestins selected for delivery of low doses by means of an IUS, or transdermally, only very active molecules can be used. An IUS approved for HRT in several countries delivers very low doses of levonorgestrel (LNG) in the uterine cavity. Nestorone® is well absorbed transdermally from a gel as well as from a metered dose transdermal system (MTDS) that sprays an invisible film on the skin. Transdermal patches combining oestradiol with either norethisterone acetate or LNG have been available for several years. Although parenteral administration of progesterone or low-dose progestins should in theory be associated with fewer side-effects than oral therapy, the long-term safety of the newer systems warrants further evaluation. [ABSTRACT FROM AUTHOR]

Currently developed progesterone receptor modulators (PRMs) are steroid-derived compounds with mild or potent antiprogestin activity. PRMs may exert a contraceptive activity by different mechanisms such as blockade of ovulation and endometrial desynchronization. Their potential clinical applications are manifold and are very promising in major public health areas, including emergency contraception, long term oestrogen-free contraception (administered alone, or in association with a progestin-only pill to improve bleeding patterns), endometriosis and myoma treatment. The mechanisms of their anti-ovulatory effects and of the endometrial modifications elicited during long term PRM treatment are still not fully elucidated. In future clinical applications, PRMs will be administered orally, via intrauterine systems or vaginal rings. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the effects of an oral contraceptive containing 3 mg drospirenone (DRSP) and 30 μg ethinyl oestradiol (EE) on somatic and psychological symptoms related to water retention, and on body weight. Methods This prospective study was performed in 26 centres in Canada over six treatment cycles. The first primary efficacy variable was the individual change in the water retention score of the Moos Menstrual Distress Questionnaire (MDQ) from baseline to the final examination in women with significant somatic symptoms related to water retention (n = 43). The second primary target variable was the change in body weight (n = 305). Results Forty-three women met the criteria for the first primary target variable. In the premenstrual phase, the score decreased from 6.49 (SEM 0.45) at baseline to 3.19 (SEM 0.54) at the final examination (p = 0.0001). The data for the menstrual phase were 4.70 (SEM 0.30) at baseline and 2.35 (SEM 0.32) at the final examination (p < 0.0001). Baseline data from 299 women were assessed for the second primary target variable. Body weight did not change significantly, having increased only by 0.14 kg (SEM 0.13) at the final visit (p = 0.3082). Conclusion An oral contraceptive containing 3 mg DRSP and 30 μg EE significantly reduced the clinical symptoms of water retention. Body weight did not change. [ABSTRACT FROM AUTHOR]

Objective: To determine the effects of monophasic oral contraceptives on the nasal respiratory epithelium in premenopausal women.Design: Prospective open clinical trial.Setting: Outpatient Family Planning Centre.Patient(s): Eighty-eight premenopausal women, with ovulatory cycle, who were planning to take oral contraceptives.Intervention(s): Baseline endovaginal ultrasound examination and blood test to measure serum progesterone to confirm ovulatory cycle. Thirty-eight women on pill containing 30 microg ethinylestradiol (EE) plus 75 microg gestodene, and 35 women on pill containing 15 microg ethinylestradiol plus 60 microg gestodene. MAIN OUTCOMES/MEASURE(S): Cytological changes on the nasal respiratory epithelium evaluated with the maturation index performed during the follicular, periovular, and luteal phases of the menstrual cycle, and on the sixth cycle of pill intake.Result(s): Hematoxylin-eosin staining for the maturation index showed similar trophic cytological aspects between the nasal and vaginal epithelium during the menstrual cycle and pill usage. Both the nasal and vaginal cytological samples showed higher maturation indexes during both the follicular and the periovular phases than during the luteal phase. Women on pill containing 15 microg EE showed lower trophic aspects in the nasal cytological samples compared with those on pill with 30 microg EE.Conclusion(s): Along with the vaginal cells, the nasal respiratory epithelium is an ovarian steroid target. The maturation index of the nasal respiratory epithelium seems to depend on the variation of the ovarian steroids during the menstrual cycle and on the iatrogenic effects of oral contraceptives. [ABSTRACT FROM AUTHOR]

The intrauterine devices (IUD) is a contraceptive method largely used as an effective, safe and economic method of contraception; IUD efficacy is demonstrated to be about 97%, and copper IUD contraceptive failure frequency is about 0.8% for the first year of use, and this is about 0.1-0.2% for the progestin IUD. IUD benefits are different; it produces a well-defined contraceptive efficacy for long time, is useful for sexual activity and is rather free from common problems. However, IUD utilization is associated with an increasing risk of pelvic infection (0.5%) in the 8 years from initial use, and the common risk of pelvic inflammatory infection (PID) is about one to two cases per year; this risk, for copper IUD users, is 0.2-0.5% per year. The possible side effects of IUD use are: pelvic pain, irregular meshes, infections, bleeding and uterine perforation; we report a uterine perforation due to IUD migration in the Retzius space, diagnosed on transvaginal ultrasonography, confirmed on CT and removed by laparoscopy. In any case, the IUD remains the mainstay of family planning measures in developing countries but, unfortunately, its association with possible serious complications, change the cost-benefit link and restrict its utilization by a large part of the general population. [ABSTRACT FROM AUTHOR]

Synthetic progestogens differ not only in their hormonal potency, but also in their spectrum of hormonal activities. Beside their progestogenic and anti-oestrogenic effects, they may exert oestrogenic, androgenic, antiandrogenic, glucocorticoid and/or anti-mineralocorticoid activities. Consequently, progestogens may influence various metabolic parameters and modulate oestrogen-induced alterations in lipid metabolism, haemostasis, and various other factors. Progestogens with androgenic properties may counteract ethinyloestradiol (EE)-induced changes in lipoprotein metabolism, but do not cause atherosclerosis in the presence of EE. Oral contraceptives (OCs) containing androgenic progestogens which attenuate the EE-dependent changes in haemostasis, may be associated with a lower risk of venous thromboembolic disease than OCs whose progestogens have a less androgenic profile. Progestogens with androgenic activity may also antagonize oestrogen-induced alterations in various other hepatic proteins and modulate the effect of EE on growth factors. Progestogens with antiandrogenic activity may enhance the beneficial effect of EE in women with hyperandrogenic manifestations. Progestogens with glucocorticoid effects may increase procoagulatory activity in the vessel wall, while progestogens with anti-mineralocorticoid activity may reduce the aldosterone-induced water-retention in some women. For most women the differences in the hormonal pattern of progestogens used in OCs are without clinical relevance, but may be useful for women predisposed for the development of certain disorders. [ABSTRACT FROM AUTHOR]

This review illustrates the principle of hormonal male contraception and gives an overview of current trials aiming at the development of a marketable hormonal contraceptive for men. The principle of male hormonal contraception is based on strong suppression of gonadotropins in order to arrest spermatogenesis at the spermatogonial stem cell level, thus leading to azoospermia or severe oligozoospermia. Until now, it has not been possible to interrupt spermatogenesis effectively without simultaneously inhibiting the production of androgens by Leydig cells, resulting in a deficiency of extra-testicular androgens. Therefore, testosterone needs to be replaced. By administering exogenous testosterone alone azoospermia can be reached in East Asians, whereas azoospermia is only achieved in two-thirds of Caucasian volunteers so that in these men an additional agent is required. Currently injectable testosterone combined with gestagens or administered as implants are being tested for possible licensing. Although scrotal and non-scrotal testosterone patches, orally administered testosterone undecanoate and testosterone gels are generally well tolerated and provide stable testosterone levels in the normal range, their use showed generally disappointing efficacy due to insufficient gonadotropin suppression. Further large multi-centre studies are required to establish the contraceptive efficacy of the most promising steroid combinations. [ABSTRACT FROM AUTHOR]

Chlormadinone acetate (CMA) is a derivative of naturally secreted progesterone that shows high affinity and activity at the progesterone receptor. It has an anti-estrogenic effect and, in contrast to natural progesterone, shows moderate anti-androgenic properties. CMA acts by blocking androgen receptors in target organs and by reducing the activity of skin 5α-reductase. It suppresses gonadotropin secretion and thereby reduces ovarian and adrenal androgen production. CMA shows high contraceptive efficacy by inhibiting ovulation due to its ability to suppress or disrupt endogenous gonadotropin secretion and, by this, inhibits follicular growth and maturation. In addition, it suppresses endometrial thickness and increases the viscosity of cervical mucus. Pharmacokinetic studies have shown rapid and almost complete absorption after oral administration, and CMA is being bound to albumin rather than SHBG (Sex-Hormone-Binding-Globulin). Multiple dosing studies have demonstrated that steady state is reached by day 7 after oral administration with peak plasma concentrations in the region of 2 ng/ml. After a single dose of CMA the half-life time is around 34 hours and after multiple dose administration approximately 38 hours. Safety studies have indicated that CMA has no clinically relevant effect on a wide range of metabolic parameters in normal subjects. Further studies in groups at high thromboembolic risk have shown that CMA alone produces a relative risk of 0.8 which is not considered significant. These results indicated the potential for CMA to be combined with ethinylestradiol in an oral contraceptive which provides highly effective contraception and excellent cycle control. [ABSTRACT FROM AUTHOR]

Design: A multicenter, retrospective study of the single-rod contraceptive implant, Implanon (NV Organon, Oss, The Netherlands), was carried out in Switzerland in 1183 women.Methods: Assessments included duration of use, bleeding pattern, side-effects and subjective acceptability and satisfaction with the method.Results: A total of 991 women (84%) had at least one follow-up visit and 306 (26%) had two visits with a mean duration between insertion and follow-up of 224 days (7.4 months) and 347 days (11.4 months), respectively. Implanon was removed prematurely in 235 women (24%), primarily because of side-effects (20%) and for family planning reasons (4%). Side-effects leading to discontinuation were mainly bleeding disturbances (45%), acne (12%) and other reasons (15%). The mean duration between insertion and removal for discontinuers was 280 days (9.2 months). Side-effects related to bleeding (visit 1) included infrequent bleeding (28%), amenorrhea (33%), prolonged bleeding (15%), and metromenorrhagia (frequent and heavy bleeding) (16%). Other reported side-effects at visit 1 included dizziness (12%), acne (11%), mood swings (8%) and headache (5%). The incidence of side-effects reported at visit 2 was generally comparable to that at visit 1.Conclusions: The results of this study show that early discontinuation of implant use is primarily due to bleeding problems. Extensive counseling before implant insertion may help to prevent this. It is also important to develop an easy solution to successfully treating progestogen-induced bleeding disturbances. [ABSTRACT FROM AUTHOR]

Objectives: To compare carbohydrate metabolism, adrenal and thyroid function during use of a combined contraceptive vaginal ring (NuvaRing, NV Organon, Oss, The Netherlands) with those of a combined oral contraceptive.Methods: Healthy women aged 18-40 years used either the vaginal ring, delivering 15 microg ethinylestradiol and 120 microg of etonogestrel per day, or a combined oral contraceptive containing 30 microg ethinylestradiol and 150 microg levonorgestrel, for six cycles. Each cycle comprised 3 weeks of use of the ring or the pill followed by 1 ring- or pill-free week. The following parameters were measured at baseline and at the end of cycles 3 and 6: carbohydrate metabolism (glucose, insulin, glycosylated hemoglobin); adrenal function (total cortisol, cortisol binding globulin, dehydroepiandrosterone sulfate); thyroid function (thyroid stimulating hormone, free thyroxine).Results: Small and similar increases in insulin were seen in both groups. Concentrations of cortisol binding globulin and total cortisol rose significantly less during ring use than during combined oral contraceptive use (cycle 3, p= 0.0002; cycle 6, p < 0.0001). Levels of dehydroepiandrosterone sulfate did not change in either group. Thyroid stimulating hormone levels increased significantly more in the ring group at cycle 3 (p = 0.0016) but free thyroxine levels were unchanged in both groups.Conclusions: Both the vaginal ring and the oral contraceptive have no clinically relevant effects on carbohydrate metabolism, adrenal or thyroid function. [ABSTRACT FROM AUTHOR]

The term progestogen has been widely utilized to indicate the general class of agents that includes both progesterone and its synthetic analogs, whereas the term progestin refers only to synthetic progestational steroids. The development of progestins has been influenced in a major way by the search for orally active hormonal contraceptives, since it is likely that hormonal contraceptives will continue to utilize a progestin, the only possible alternative being represented by the utilization of antiprogestins. Synthetic progestogens in clinical use today belong to three main chemical families: progesterone derivatives (progesterone, retro-progesterone, 19-norprogesterone and 17α-hydroxyprogesterone); gonane and 19-nortestosterone derivatives (norethisterone, levonorgestrel, desogestrel, gestodene, norgestimate); a spironolactone derivative. Biological potency of progestogens varies depending on the end-point measured, usually ovulation inhibition and endometrial transformation; with both these tests, the most active compounds are all gonane derivatives, with a potency over a 100 times that of the natural hormone. When administered in adequate doses, a progestin inhibits fertility by inhibiting ovulation. This action is mainly exerted at the hypothalamic level where, physiologically, progesterone decreases the number of LH pulses. When progestogens are delivered directly to the uterine cavity, their action seems to be purely local. It has been amply proven that - even when administered in doses that do not constantly inhibit ovulation - a progestin can still remain effective as a contraceptive by acting at the level of the cervical mucus and, at least in part, of the endometrium. Progestogens utilized today differ largely in their pharmacokinetics. In general, after intake, these compounds are rapidly absorbed and distributed so that peak serum concentrations are reached between 1 and 4 h. Third-generation progestins (desogestrel, gestodene, norgestimate) have common characteristics: a higher affinity for progesterone receptors than their predecessors, a lower affinity for androgen receptors, a higher selectivity of action, a higher central inhibitory activity, a higher potency at the level of the endometrium, and an overall metabolic neutrality, in terms of effects on lipid and carbohydrate metabolism. In general, progestins can induce two types of adverse effects: changes in lipid metabolism and bleeding irregularities. Whereas the newer compounds seem to have overcome the first of these adverse effects, the second remains untouched: to this day, proper cycle control can only be achieved with combined hormonal contraceptives. [ABSTRACT FROM AUTHOR]

Acne and seborrhea (or facial oiliness) are related androgenic skin disorders which affect a high proportion of women after menarche. They can have a negative effect on psychological well-being and social life. Androgens play an important role in the pathogenesis of acne through the stimulation of sebum secretion, increasing sebaceous gland size and possibly through follicular hyperkeratinization. Conversely, estrogens decrease sebum production by suppressing gonadotropin release and androgen production and increasing sex hormone binding globulin production. One of the treatment options for these conditions is hormonal therapy, especially for women who require contraception. The effect of combined oral contraceptives in androgenic skin disorders depends on their estrogen:progestogen balance and on the antiestrogenic activity of the progestogen component. Improved understanding of what women value about oral contraceptives suggests that the choice of product should be tailored as much as possible to the individual. Several combined oral contraceptives containing new-generation progestogens (e.g. desogestrel, gestodene) or progestational antiandrogens (e.g. cyproterone acetate, chlormadinone acetate) have demonstrated efficacy in the treatment of women with acne, although comparisons between trials are difficult because of differing endpoints. Seborrhea has been less well studied, but the few studies that are available show an improvement in women with this condition using combined oral contraceptives. [ABSTRACT FROM AUTHOR]

Aim: The primary objective of the study was to evaluate the continuation rates of a relatively new long-acting method of contraception, Implanon1. The secondary objective was to study discontinuations related to bleeding problems and their management. Method A retrospective review of records of women fitted with Implanon was undertaken during February 2000-January 2003. Results: Results from the secondary objective will be the subject of a separate communication. Of the 147 implants fitted, 132 records could be retrieved; of these, 97% of the women had pre-insertion counselling by the clinician. The most common indications for Implanon usage were choice of a long-acting method, unhappy experience with other contraceptive methods and suboptimal compliance with contraceptive pills and injectables. The median age of fitting was 25 years and 36% of the women were nulliparous. No problems were experienced with fitting or removal of implants. Twenty (15%) women were lost to follow-up. Twenty-two implants were removed by the end of the study period, with 12 (60%) removals attributed to prolonged heavy/light bleeding. There were no known pregnancies during the study. Given that 15% of the women could not be followed up or contacted, the assumed lifetimes of Implanon using the Kaplan-Meier method are 0.90 (95% confidence interval 0.82-0.95) at 12 months, 0.80 (0.67-0.88) at 24 months and 0.75 (0.58- 0.85) at 35 months. The confirmed lifetimes are 0.84 (0.71-0.91) at 12 months, 0.63 (0.42- 0.78) at 24 months and 0.53 (0.28-0.73) at 35 months. Conclusion: Although not free of side-effects, Implanon can be a good choice for women who are properly informed and counselled and seek long-term 'forgettable' contraception. [ABSTRACT FROM AUTHOR]

The Consensus Statement on Emergency Contraception recommends the collection of data within each country in order to facilitate the use of emergency contraception; this has led us to design a prospective observational study with a view to identifying the reality in Spain regarding emergency contraception. We have conducted a national observational study including 4390 cases of requests for the prescription of emergency contraception in the entire Spanish territory, collected by means of a questionnaire completed by the person prescribing the emergency contraception between April and December 2002. The mean age of the women requesting emergency contraception was 23 years, with 35.1% of these being adolescents and 71% of them under the age of 24 years. Of the applicants, 40% reported that they were students and 31.8% were working. The educational level of studies was medium or higher. Emergency contraception had previously been used by 19.8% of the women and, of these, 75% used it on a single occasion. The main reason put forward for requesting emergency contraception was condom breakage (68.7%), followed by the failure to use any contraceptive measures whatsoever (15.4%). The Spanish women requesting emergency contraception are young students and resort to this method on one occasion. [ABSTRACT FROM AUTHOR]

As well as providing reliable contraception, modern low-dose oral contraceptives may offer some non-contraceptive advantages. Positive effects on problems such as edema with weight increase and breast tenderness, bloating, dysmenorrhea, and an improvement in skin and hair condition have been reported in several studies using an oral contraceptive containing drospirenone. If these disorders are cycle-dependent, use of the contraceptive in an extended regimen may be of additional benefit. The study reported in this paper followed 1433 women, 175 of whom took the drospirenone-containing pill continuously for between 42 and 126 days. Some symptoms of the premenstrual syndrome were influenced very satisfactorily by administration in an extended regimen. [ABSTRACT FROM AUTHOR]

Objectives To establish why university students in Finland, who have easy access to well-affordable health services, still use hormonal emergency contraception. Method All students who sought emergency contraception in the Tampere Student Health Station during the period from 1 September 2000 to 31 December 2001 received a questionnaire on their use of it. Of the total, 114 (67%) were returned. Results Two-thirds of respondents experienced condom failure, and the remainder used no contraception. In open answers, respondents gave many explanations as to why they had used no contraception, e.g. having been over-passionate or drunk. Conclusion Finnish students use emergency contraception, but to no great extent. Our results indicate that service providers should pay attention to sexual health in the full sense but not omit to give detailed advice on condom use during counselling. [ABSTRACT FROM AUTHOR]

Objective To compare the influence of oral hormonal contraceptives (OCs) and the use of intrauterine contraceptive devices (IUDs) on the modification of sexual desire. Materials and methods A prospective observational study of 1073 women using OCs or an IUD at the Family Planning Center 'Marina Alta' in Alicante, Spain. In order to evaluate the relative risk regarding the decrease in libido attributed to each contraceptive method, a logistic regression analysis was undertaken which considered the factors of age adjustment, level of studies, family planning information, relationship with partner, age when sexual relationships were initiated, parity, contraceptive method previously used and the duration of use of the contraceptive method. Results No differences in the decrease of sexual desire were observed between the use of the OC and IUD (odds ratio (OR) 1.32; 95% confidence interval (CI) 0.70-2.49), yet differences were noted, however, in relation to age (OR 1.05; 95% CI 1.01-1.10). Although these differences were not statistically significant, a high level of awareness regarding family planning was shown to increase sexual desire when compared to a lower level of information on this subject (OR 0.64; 95% CI 0.41-1.01). Sexual desire was seen to decrease if the quality of the relationship with the partner was average (OR 2.24; 95% CI 1.36-3.69) or poor (OR 4.69; 95% CI 1.93-11.4). Nulliparous women showed a greater decrease in sexual desire in relation to women who had already given birth (OR 1.57; 95% CI 1.00-2.47). Sexual desire was greater if the contraceptive method had already been in use for 6-12 months (OR 0.41; 95% CI 0.17-0.98). Conclusions Sexual desire does not vary in relation to the use of OCs or IUDs, yet it does decrease with age, in nulliparous women and in those with an average or poor relationship with their partner. Furthermore, sexual desire shows an increase between the first 6 and 12 months of contraceptive treatment. [ABSTRACT FROM AUTHOR]

The author reflects on the oestrogen, a new addition in the combined oral contraceptives. He discusses that mestranol was the first oral contraceptive made and was later replaced by active metabolite ethinylestradiol (EE). He also discusses that oral contraceptives are incorporated by two types including progestogen and an oestrogen. He concludes oestrogenic priming are identical to native endigenous molecule and side effects depend on the modulation exerted by progestogen added.