Menstrual cycle phases and dosage of synthetic hormonal contraceptives influence diurnal rhythm characteristics of distal skin temperature.

This study aimed to explore how natural menstrual cycle phases and dosage of oral hormonal contraceptives (OC) influence the diurnal rhythm of distal skin temperature (DST) under real-life conditions. Participants were 41 healthy females (23.9 ± 2.48 y), comprising 27 females taking monophasic hormonal oral contraceptives (OC users) and 14 females with menstrual cycles (non-OC users). Wrist DST was continuously recorded and averaged over two consecutive 24-hour days during (pseudo)follicular and (pseudo)luteal menstrual phases. Diurnal rhythm characteristics, i.e. acrophase and amplitude, describing timing and strength of the DST rhythm, respectively, were calculated using cosinor analysis. Results show that non-OC users experienced earlier diurnal DST maximum (acrophase, p = 0.019) and larger amplitude (p = 0.016) during the luteal phase than during the follicular phase. This was observed in most (71.4%) but not all individuals. The OC users showed no differences in acrophase or amplitude between pseudoluteal and pseudofollicular phases. OC users taking a higher dosage of progestin displayed a larger amplitude for DST rhythm during the pseudoluteal phase (p = 0.009), while estrogen dosage had no effect. In conclusion, monophasic OC cause changes in diurnal DST rhythm, similar to those observed in the luteal phase of females with menstrual cycles, suggesting that synthetic progestins act in a similar manner on skin thermoregulation as progesterone does.

Should Combined Hormonal Contraception Be Stopped in the Perioperative Period?

Should Combined Hormonal Contraception Be Stopped in the Perioperative Period?A 34-year-old woman is scheduled to undergo surgery to manage a torn anterior cruciate ligament in her left knee. Her only medication is an estrogen- and progestin-containing oral contraceptive pill (OCP). Should she stop her combined oral contraception to reduce the risk of a postoperative blood clot?

Does exogenous female sex hormone administration affect the rate of tooth movement and root resorption? A systematic review of animal studies.

BACKGROUND: The long-term use of contraceptive methods that contain estrogens, progestogens or combinations of the above among women aged 15 to 49 years is extensive. Both estrogens and progestogens affect bone metabolism. OBJECTIVE: To systematically investigate and appraise the quality of the available evidence from animal studies regarding the impact of exogenous administration of female sex hormones on the rate of orthodontic tooth movement and root resorption. SEARCH METHODS: Search without restriction in seven databases (including grey literature) and hand searching were performed until May 2021. SELECTION CRITERIA: We looked for controlled animal studies investigating the effect from exogenous administration of formulations containing female sex hormones on the rate of orthodontic tooth movement and root resorption. DATA COLLECTION AND ANALYSIS: After study retrieval and selection, relevant data was extracted, and the risk of bias was assessed using the SYRCLE's Risk of Bias Tool. The quality of available evidence was assessed with the Grades of Recommendation, Assessment, Development, and Evaluation. RESULTS: Three studies were identified, all being at unclear risk of bias. Overall, administration of progesterone and the combinations of estradiol with norgestrel and desogestrel were shown to significantly decrease the rate of orthodontic tooth movement when given for longer periods (>3 weeks). Inconsistent information was detected for shorter periods of consumption. Estradiol, with desogestrel use, resulted in less root resorption. The quality of the available evidence was considered to be low. CONCLUSIONS: Exogenous administration of female sex hormones may decelerate in the long term the rate of tooth movement and decrease orthodontically induced root resorption in animals. Until more information becomes available, an orthodontist should be able to identify a patient consuming such substances and understand the potential clinical implications and adverse effects that may arise. REGISTRATION: PROSPERO: CRD42017078208; https://clinicaltrials.gov/.

Overall and bleeding-related discontinuation rates of a new oral contraceptive containing 4 mg drospirenone only in a 24/4 regimen and comparison to 0.075 mg desogestrel.

OBJECTIVES: Progestin-only pills do not increase the risk of venous thromboembolism, stroke, and myocardial infarction but are associated with poor cycle control. A novel estrogen-free pill containing only drospirenone (DRSP) to improve bleeding patterns and tolerability and reduce discontinuation rates has been introduced into the market. The present study aims to describe the improvement in the acceptability of this DRSP-only pill, e.g. regarding the bleeding profile and the reduction in discontinuation rates due to unacceptable bleeding compared to desogestrel (DSG). STUDY DESIGN: Double-blind, double-dummy prospective phase III study in healthy women aged 18-45 years evaluating a total of 858 women with 6691 DRSP and 332 women with 2487 DSG treatment cycles. RESULTS: Overall, 82 (9.6%) women in the DRSP group and 44 (13.3%) women in the DSG group experienced treatment-emergent adverse events (TEAEs) leading to premature termination of the trial meaning that 32% more women in the DRSP group finished the trial in comparison to the DSG group (based on the AUC of Kaplan-Meier's curves). Discontinuation rates due to abnormal bleeding were 3.7% for DRSP and 7.3% for DSG users. This is a 55.7% lower discontinuation rate in the DRSP group compared to the DSG group. CONCLUSIONS: This report describes the improvement in acceptability and bleeding profile of women using the new DRSP-only oral contraceptive compared to DSG, providing a better quality of life and adherence to the contraceptive method as demonstrated by lower discontinuation rates of women using the estrogen-free DRSP-only pill.

Trends in the use of hormonal contraception in Estonia 2005-2019 and the risk of arterial and venous thromboembolism: a population-based study.

PURPOSE: To describe trends in hormonal contraceptive use, incidence of thromboembolism and presence of risk factors for thromboembolism among the users in Estonia. MATERIAL AND METHODS: Data of 223 312 female patients aged 15-49 years in 2005-2019 from national health insurance databases was derived. Annual prevalence rates of hormonal contraceptive users, incidence rates of thromboembolism and prevalence rates of risk factors were calculated. RESULTS: Between 2005-2019 usage of progestogen-only contraceptives (POCs) increased steadily (from 24 to 135 users per 1000 population), whereas combined hormonal contraceptive (CHC) use declined (from 209 in 2012 to 161 users per 1000 population in 2019). During the study period, 390 cases of venous thromboembolism and 108 arterial thromboembolism coincided with hormonal contraceptive use. Incidence rate for venous thromboembolism was 5.0 (95% CI 4.5-5.5) and for arterial thromboembolism 1.4 per 10 000 person-years (95% CI 1.1-1.7) among hormonal contraceptive users. Age adjusted incidence of venous thromboembolism among CHC users was 5.8 (95% CI 4.1-8.2) times higher than in POC users. Among CHC users, 10.3% had more than one risk factor for thrombosis. CONCLUSIONS: In regards to the risk of thromboembolism, wider use of POCs and declining prevalence of CHCs in Estonia is positive trend. Still, women with history of thrombosis receiving CHC is a serious concern.

Duration, recency, and type of hormonal contraceptive use and antimüllerian hormone levels.

OBJECTIVE: To assess whether the duration, recency, or type of hormonal contraceptive used is associated with antimüllerian hormone (AMH) levels, given that the existing literature regarding the association between hormonal contraceptive use and AMH levels is inconsistent. DESIGN: Cross-sectional study. SETTING: Baseline data from the Study of the Environment, Lifestyle and Fibroids Study, a 5-year longitudinal study of African American women. PATIENT(S): The patients were 1,643 African American women aged 23-35 years at the time of blood drawing (2010-2012). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Serum AMH level was measured by an ultrasensitive enzyme-linked immunosorbent assay. Linear regression models were used to estimate percent differences in mean AMH levels and 95% confidence intervals (CIs) according to use of hormonal contraceptives, with adjustment for potential confounders. RESULT(S): In multivariable-adjusted analyses, current users of hormonal contraceptives had 25.2% lower mean AMH levels than non-users of hormonal contraceptives (95% CI: -35.3%, -13.6%). There was little difference in AMH levels between former users and non-users of hormonal contraceptives (-4.4%; 95% CI: -16.3%, 9.0%). AMH levels were not appreciably associated with cumulative duration of use among former users or time since last use among non-current users. Current users of combined oral contraceptives (-24.0%; 95% CI: -36.6%, -8.9%), vaginal ring (-64.8%; 95% CI: -75.4%, -49.6%), and depot medroxyprogesterone acetate (-26.7%; 95% CI: -41.0%, -8.9%) had lower mean AMH levels than non-users. CONCLUSION(S): The present data suggest that AMH levels are significantly lower among current users of most forms of hormonal contraceptives, but that the suppressive effect of hormonal contraceptives on AMH levels is reversible.

Dienogest reduces endometrioma volume and endometriosis-related pain symptoms.

This study aimed to evaluate the efficacy and adverse effects of dienogest for the treatment of endometriomas. Dienogest (2 mg/day) was administered to patients with endometrioma continuously through the 6-month study period. The patients were prospectively examined on the efficacy and side effects at baseline, at third months, and sixth months of the treatment. Twenty-four out of 30 patients were able to complete the study. The mean volume of the endometrioma decreased significantly from 112.63 ± 161.31 cm³ at baseline to 65.47 ± 95.69 cm³ at a 6-month follow-up (-41%) (p = .005). The VAS score for pelvic pain decreased significantly from 7.50 to 3.00 (p < .001) at the sixth months of treatment. The most common side effects were menstrual irregularities. Laboratory parameters did not change during the study. Dienogest considered being effective for 6 months of use in decreasing the size of endometrioma, reducing endometriosis-associated pain with a favourable safety and tolerability profile.Impact statementWhat is already known on this subject? Laparoscopic excisional surgery for endometrioma is currently the most valid approach in the treatment of endometriomas. However, there are concerns about ovarian reserve damage during surgery.What do the results of this study add? Dienogest considered being effective in decreasing the size of endometrioma, reducing endometriosis-associated pain with a favourable safety and tolerability profile. Long-term use of dienogest in younger patients with endometriomas who are yet to give birth may reduce the possibility of surgery by reducing the size of the endometriomas and may preserve ovarian reserve.What are the implications of these findings for clinical practice and/or further research? Dienogest may reduce the incidence of infectious complications such as pelvic abscess after oocyte retrieval and the surgical procedures in infertile patients with endometrioma.

Initiating Hormonal Contraception.

Most patients can safely begin using hormonal contraception at any point in their menstrual cycle. An evidence-based, flexible, patient-centered approach to initiating contraception promotes health and enhances patients' reproductive autonomy. A recent Papanicolaou test is not necessary before prescribing hormonal contraception. Most patients can begin using progestin-only contraceptives immediately after childbirth. Patients can begin any appropriate contraceptive method immediately after an abortion or early pregnancy loss, except for an intrauterine device following septic abortion. Delaying contraception to wait for the next menses or for an appointment creates unnecessary barriers for patients. Clinicians can facilitate the use of hormonal contraception by providing anticipatory guidance about common side effects (e.g., spotting, other menstrual cycle changes), giving comprehensive information about available contraceptive choices, honoring patients' preferences, and eliminating office-related barriers. Prescribing or dispensing a one-year supply of contraceptives lowers costs and improves adherence. Counseling via telemedicine or a patient portal eliminates unnecessary office visits.

Lifestyle modifications alone or combined with hormonal contraceptives improve sexual dysfunction in women with polycystic ovary syndrome.

OBJECTIVE: To describe the prevalence of female sexual dysfunction in a well-defined polycystic ovary syndrome (PCOS) population, and to assess the impact of common PCOS treatments on sexual function. DESIGN: Secondary analysis of a randomized controlled trial, oral contraceptive pills and weight loss in PCOS. SETTING: Two academic medical centers. PATIENTS: Women with PCOS (N = 114) defined by the Rotterdam criteria. INTERVENTIONS: Continuous oral contraceptive pill (OCP) or intensive lifestyle modification (Lifestyle) or the combination (Combined) for 16 weeks. MAIN OUTCOME MEASURES: Change in Female Sexual Function Index (FSFI) and Female Sexual Distress Scale-Revised (FSDS-R) scores after 16 weeks. RESULTS: There was no change in total FSFI or FSDS-R score in any treatment group; however, an increase in the FSFI desire domain subscore was observed in the Lifestyle and Combined treatments, indicating improved sexual desire over the 16-week period. Overall, 33 participants (28.9%) met criteria for sexual dysfunction by FSFI criteria (baseline score ≤26.55). Among this group, FSFI score improved after 16 weeks of Lifestyle and Combined treatments. There was no change in prevalence of sexual dysfunction in treatment groups at 16 weeks. Use of OCPs did not alter FSFI scores. CONCLUSION(S): Female sexual dysfunction is highly prevalent among women with PCOS. Our findings suggest that common treatments for PCOS, including intensive lifestyle modification and the combination of intensive lifestyle modification and OCPs, have the potential to improve sexual function in these women; the mechanism for these improvements is likely multifactorial. CLINICAL TRIAL REGISTRATION NUMBER: NCT00704912.

The Perfect Balance? Managing Heavy Menstrual Bleeding and Dysmenorrhea in a Patient with Hereditary Hemochromatosis and von Willebrand Disease.

BACKGROUND: Hereditary hemochromatosis typically presents in adulthood with organ damage secondary to iron overload. In women, menstrual periods are a protective mechanism allowing for monthly loss of iron stores. CASE: We report the case of a female adolescent whose family history, clinical presentation, and laboratory investigation revealed a diagnosis of hereditary hemochromatosis and von Willebrand disease. For control of heavy menstrual bleeding, menstrual suppression was started with a subsequent increase of her ferritin levels. SUMMARY AND CONCLUSION: No significant data exist regarding the management of women with hereditary hemochromatosis who require menstrual suppression. This case highlights the difficulty in balancing the need for hormonal menstrual suppression with its effect on treatment choices, monitoring, and managing iron levels.

Hepcidin response to interval running exercise is not affected by oral contraceptive phase in endurance-trained women.

The use of oral contraceptives (OCs) by female athletes may lead to improved iron status, possibly through the regulation of hepcidin by sex hormones. The present work investigates the response of hepcidin and interleukin-6 (IL-6) to an interval exercise in both phases of the OC cycle. Sixteen endurance-trained OC users (age 25.3 ± 4.7 years; height 162.4 ± 5.7 cm; body mass 56.0 ± 5.7 kg; body fat percentage 24.8 ± 6.0%; peak oxygen consumption [VO2peak ]: 47.4 ± 5.5 mL min-1 kg-1 ) followed an identical interval running protocol during the withdrawal and active pill phases of the OC cycle. This protocol consisted of 8 × 3 minutes bouts at 85% VO2peak speed with 90 seconds recovery intervals. Blood samples were collected pre-exercise, and at 0 hour, 3 hours, and 24 hours post-exercise. Pre-exercise 17ß-estradiol was lower (P = .001) during the active pill than the withdrawal phase (7.91 ± 1.81 vs 29.36 ± 6.45 pg/mL [mean ± SEM]). No differences were seen between the OC phases with respect to hepcidin or IL-6 concentrations, whether taking all time points together or separately. However, within the withdrawal phase, hepcidin concentrations were higher at 3 hours post-exercise (3.33 ± 0.95 nmol/L) than at pre-exercise (1.04 ± 0.20 nmol/L; P = .005) and 0 hour post-exercise (1.41 ± 0.38 nmol/L; P = .045). Within both OC phases, IL-6 was higher at 0 hour post-exercise than at any other time point (P < .05). Similar trends in hepcidin and IL-6 concentrations were seen at the different time points during both OC phases. OC use led to low 17ß-estradiol concentrations during the active pill phase but did not affect hepcidin. This does not, however, rule out estradiol affecting hepcidin levels.

Oral contraceptive use by formulation and endometrial cancer risk among women born in 1947-1964: The Nurses' Health Study II, a prospective cohort study.

Oral contraceptives (OCs) have been associated with long-term lower endometrial cancer risk; relatively little is known about associations with more recent OC formulations and associations with longer-term risk. A total of 107,069 women from the Nurses' Health Study II recalled OC use from age 13 to baseline (1989); biennial questionnaires updated data on OC use until 2009. OCs were classified by estrogen and progestin type, dose, and potency based on reported brand. 864 incident endometrial cancer cases were identified through 2017. Multivariable Cox proportional hazards models estimated hazard ratios (HR) and 95% confidence intervals [95% CI] for the association of OC use with endometrial cancer risk. OC use was associated with lower endometrial cancer risk (ever use, HR 0.77 [95% CI 0.65-0.91]; >10 years of use, 0.43 [0.32-0.58] vs. never OC use). Inverse associations for duration were evident regardless of time since last use. Longer durations (> 5 years) of ethinyl estradiol (0.52 [0.41-0.67]) and second-generation progestins (0.43 [0.30-0.61]), both versus never use, were more strongly associated with lower risk than mestranol (0.66 [0.50-0.88], p-het = 0.01) and first-generation progestins (0.62 [0.49-0.78], p-het = 0.03). Inverse associations were generally observed for cross-classified cumulative average estrogen and progestin dose and potency (< vs. ≥ median; ever use vs. never OC use), with the exception of high estrogen and low progestin dose. OCs were associated with lower endometrial cancer risk, independent of time since last use. Use of ethinyl estradiol and second-generation progestins were more strongly inversely associated with risk compared with older formulations.

[The French "pill scare": Did women go to a gynecologist more often to have an easier access to the IUD?] / La « crise des pilules ¼ en France : les femmes ont-elles davantage consulté un.e gynécologue afin d'accéder plus facilement au DIU ?

BACKGROUND: In December 2012, a media controversy about negative side-effects of oral contraceptives on women's health, also called "pill scare", broke out in France. While several analyses highlighted a change in women's contraceptive practices following this media controversy, no analysis has been conducted to determine the possible changes in their choices of health professionals and its repercussions on their contraceptive use. METHODS: Our study is based on data from three population-based cross-sectional surveys conducted in 2010, 2013 and 2016 (Fecond 2010, Fecond 2013 and Baromètre Santé 2016) that collected information on women's contraceptive practices and the specialties of the health professionals having prescribed the methods they were using. RESULTS: Between 2010 and 2016, women went to a gynecologist or a midwife more often than to a general practitioner for prescription of a reversible contraceptive method. However, their changes in visiting prescribers did not explain the changes in their contraceptive practices observed over the period. In 2016, access to health professional remained largely dependent on women's socio-demographic characteristics: older ones and those from a more privileged social background or living in urban areas were more likely to consult a gynecologist for prescription of their contraceptive method. On the other hand, consultations of midwives for contraceptive prescription were more frequent among women with children and among those who relied on public health insurance alone. CONCLUSION: Following the "pill scare" that occurred in France in December 2012, the decision by some women to use the IUD instead of the pill led them to change health professionals, and also led practitioners to change their prescribing practices.

Effects of progestin-only contraceptives on the endometrium.

INTRODUCTION: The contraceptive activity of synthetic progestins is mediated through three basic mechanisms: (a) An anti-gonadotrophic action leading to the inhibition of ovulation; (b) Changes in cervical mucus characteristics that inhibit sperm penetration and (c) desynchronization of the endometrial picture necessary for implantation. AREAS COVERED: Mechanisms involved in the progestin-induced endometrium desynchronization are individually reviewed for each of the routes of administration and, whenever possible, by individual members of the various families of synthetic progestin derivatives. EXPERT OPINION: For contraceptive purposes, progestins are today administered through several routes: orally, as injections, subdermally and via the vagina or the uterine cavity. Given this variety of modalities, their effects may differ, depending on the route of administration, concentration reached at the level of the endometrium and the duration of use. These are characterized by inactivation of the endometrium. Progestin-only contraception provides a safe and effective control of fertility regulation, although, they are associated with the problem of endometrial break through bleeding that may lead to discontinuation. Unfortunately, in spite of a major research effort over two decades, there is not, as yet, an established long-term intervention available to manage bleeding irregularities, making mandatory a deeper understanding of the mechanisms involved is required.

Hormonal Contraception and Bone Health in Adolescents.

Hormonal contraception is prescribed commonly to adolescents for myriad indications from pregnancy prevention to treatment for acne, hirsutism or dysmenorrhea. Although use of these hormones generally has no effect or benefits bone health in mature premenopausal women, the same may not be true for adolescents. The teen years are a critical period for acquiring peak bone strength. Sex hormones, growth hormone, and insulin-like growth factors (IGFs) interact to modulate the changes in bone size, geometry, mineral content, and microarchitecture that determine skeletal strength. Combined oral contraceptives (COCs) and intramuscular depo medroxyprogesterone (DMPA) can compromise the expected gains in adolescence by altering estrogen and IGF concentrations. Use of these medications has been associated with slower accrual of bone mineral density (BMD) and increased fracture risk in some studies. Far less is known about the skeletal effects of the newer long acting reversible contraceptives (LARCs). This review takes a critical look at the gaps in current knowledge of the skeletal effects of COCs, DMPA, and LARCs and underscores the need for additional research.

Drospirenone 4 mg-only pill (DOP) in 24+4 regimen: a new option for oral contraception.

INTRODUCTION: The use of progestin-only pills (POPs) is still relatively infrequent, mainly for their unpredictable effect on menstrual bleeding. A new POP consisting of 4 mg drospirenone (DRSP) for 24 days plus 4-day hormone-free interval has been developed to address this need. DRSP is a potent progestin analogue of spironolactone, with antiandrogenic and antimineralocorticoid properties. AREAS COVERED: This is a narrative review of the available data on the pharmacotherapy of the new DRSP-only pill. The research includes aspects of pharmacokinetics/pharmacodynamics of the compound: the main focus is on the clinical effects of DRSP-only pill in terms of contraceptive efficacy, haemostatic effect, safety, tolerability and bleeding patterns. EXPERT OPINION: The DRSP-only pill presents a similar Pearl Index to that of common combined hormonal contraceptives: it is a POP with a better bleeding profile than traditional POPs (higher rates of scheduled bleedings and much lower rates of unscheduled intracyclic bleeding/spotting) which could increase its acceptability and the panorama of possible users. For these reasons, DRSP-only pill represents a real step forward in oral contraception with only progestins, even if the bleeding patterns during its use are still different to oestrogen-containing products (i.e. lower rates of scheduled bleedings and higher rate of amenorrhea).

Reasons for and experience in obtaining pharmacist prescribed contraception.

OBJECTIVE: To describe reasons for and experiences with obtaining contraception from pharmacists. STUDY DESIGN: Cross-sectional survey. RESULTS: Our sample included 426 women presenting for hormonal contraception (n = 150 pharmacist prescribers). The most common reasons women chose to obtain their contraception from a pharmacist were because no appointment was required (25%) or their prescription had lapsed (24%). Women receiving contraception from pharmacists were highly satisfied (95.3% vs 100.0%; p = 0.007). Women recalled similar side-effects counseling points regardless of prescriber type (p = 0.30). CONCLUSION: Women chose to obtain contraceptive care at the pharmacy because it was timely and convenient.