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Concept: Menstrual cycle

703

Background Texas is one of several states that have barred Planned Parenthood affiliates from providing health care services with the use of public funds. After the federal government refused to allow (and courts blocked) the exclusion of Planned Parenthood affiliates from the Texas Medicaid fee-for-service family-planning program, Texas excluded them from a state-funded replacement program, effective January 1, 2013. We assessed rates of contraceptive-method provision, method continuation through the program, and childbirth covered by Medicaid before and after the Planned Parenthood exclusion. Methods We used all program claims from 2011 through 2014 to examine changes in the number of claims for contraceptives according to method for 2 years before and 2 years after the exclusion. Among women using injectable contraceptives at baseline, we observed rates of contraceptive continuation through the program and of childbirth covered by Medicaid. We used the difference-in-differences method to compare outcomes in counties with Planned Parenthood affiliates with outcomes in those without such affiliates. Results After the Planned Parenthood exclusion, there were estimated reductions in the number of claims from 1042 to 672 (relative reduction, 35.5%) for long-acting, reversible contraceptives and from 6832 to 4708 (relative reduction, 31.1%) for injectable contraceptives (P<0.001 for both comparisons). There was no significant change in the number of claims for short-acting hormonal contraceptive methods during this period. Among women using injectable contraceptives, the percentage of women who returned for a subsequent on-time contraceptive injection decreased from 56.9% among those whose subsequent injections were due before the exclusion to 37.7% among those whose subsequent injections were due after the exclusion in the counties with Planned Parenthood affiliates but increased from 54.9% to 58.5% in the counties without such affiliates (estimated difference in differences in counties with affiliates as compared with those without affiliates, -22.9 percentage points; P<0.001). During this period in counties with Planned Parenthood affiliates, the rate of childbirth covered by Medicaid increased by 1.9 percentage points (a relative increase of 27.1% from baseline) within 18 months after the claim (P=0.01). Conclusions The exclusion of Planned Parenthood affiliates from a state-funded replacement for a Medicaid fee-for-service program in Texas was associated with adverse changes in the provision of contraception. For women using injectable contraceptives, there was a reduction in the rate of contraceptive continuation and an increase in the rate of childbirth covered by Medicaid. (Funded by the Susan T. Buffett Foundation.).

Concepts: Pregnancy, Birth control, Emergency contraception, Hormonal contraception, Combined oral contraceptive pill, Menstrual cycle, Sex education, Combined injectable contraceptive

347

Are parity and the timing of menarche associated with premature and early natural menopause?

Concepts: Menopause, Menstrual cycle, Menarche

184

An important problem in reproductive medicine is deciding when people who have failed to become pregnant without medical assistance should begin investigation and treatment. This study describes a computational approach to determining what can be deduced about a couple’s future chances of pregnancy from the number of menstrual cycles over which they have been trying to conceive. The starting point is that a couple’s fertility is inherently uncertain. This uncertainty is modelled as a probability distribution for the chance of conceiving in each menstrual cycle. We have developed a general numerical computational method, which uses Bayes' theorem to generate a posterior distribution for a couple’s chance of conceiving in each cycle, conditional on the number of previous cycles of attempted conception. When various metrics of a couple’s expected chances of pregnancy were computed as a function of the number of cycles over which they had been trying to conceive, we found good fits to observed data on time to pregnancy for different populations. The commonly-used standard of 12 cycles of non-conception as an indicator of subfertility was found to be reasonably robust, though a larger or smaller number of cycles may be more appropriate depending on the population from which a couple is drawn and the precise subfertility metric which is most relevant, for example the probability of conception in the next cycle or the next 12 cycles. We have also applied our computational method to model the impact of female reproductive ageing. Results indicate that, for women over the age of 35, it may be appropriate to start investigation and treatment more quickly than for younger women. Ignoring reproductive decline during the period of attempted conception added up to two cycles to the computed number of cycles before reaching a metric of subfertility.

Concepts: Pregnancy, Fertility, Menstrual cycle, Endometrium, Progesterone, Conditional probability, Bayes' theorem, Pregnancy test

179

Satellite temperature measurements do not support the recent claim of a “leveling off of warming” over the past two decades. Tropospheric warming trends over recent 20-year periods are always significantly larger (at the 10% level or better) than model estimates of 20-year trends arising from natural internal variability. Over the full 38-year period of the satellite record, the separation between observed warming and internal variability estimates is even clearer. In two out of three recent satellite datasets, the tropospheric warming from 1979 to 2016 is unprecedented relative to internally generated temperature trends on the 38-year timescale.

Concepts: Menstrual cycle, Period, Nature, Satellite temperature measurements

174

Previous research has documented shifts in women’s attractions to their romantic partner and to men other than their partner across the ovulation cycle, contingent on the degree to which her partner displays hypothesized indicators of high-fitness genes. The current study set out to replicate and extend this finding. Forty-one couples in which the woman was naturally cycling participated. Female partners reported their feelings of in-pair attraction and extra-pair attraction on two occasions, once on a low-fertility day of the cycle and once on a high-fertility day of the cycle just prior to ovulation. Ovulation was confirmed using luteinizing hormone tests. We collected two measures of male partner sexual attractiveness. First, the women in the study rated their partner’s sexual attractiveness. Second, we photographed the partners and had the photos independently rated for attractiveness. Shifts in women’s in-pair attractions across the cycle were significantly moderated by women’s ratings of partner sexual attractiveness, such that the less sexually attractive women rated their partner, the less in-pair attraction they reported at high fertility compared with low fertility (partial r = .37, p(dir) = .01). Shifts in women’s extra-pair attractions across the cycle were significantly moderated by third-party ratings of partner attractiveness, such that the less attractive the partner was, the more extra-pair attraction women reported at high relative to low fertility (partial r = -.33, p(dir) = .03). In line with previous findings, we found support for the hypothesis that the degree to which a woman’s romantic partner displays indicators of high-fitness genes affects women’s attractions to their own partner and other men at high fertility.

Concepts: Sexual intercourse, Estrogen, Luteinizing hormone, Menstrual cycle, Woman, Ovulation, Sexuality, Physical attractiveness

173

Volumes of paracardial adipose tissue (PAT) and epicardial adipose tissue (EAT) are greater after menopause. Interestingly, PAT but not EAT is associated with estradiol decline, suggesting a potential role of menopause in PAT accumulation. We assessed whether volumes of heart fat depot (EAT and PAT) were associated with coronary artery calcification (CAC) in women at midlife and whether these associations were modified by menopausal status and estradiol levels.

Concepts: Hormone replacement therapy, Coronary artery disease, Middle age, Heart, Menopause, Estrogen, Luteinizing hormone, Menstrual cycle

169

Primodos was a hormone pregnancy test used between 1958-1978 that has been implicated with causing a range of birth defects ever since. Though Primodos is no longer used, it’s components, Norethisterone acetate and Ethinyl estradiol, are used in other medications today including treatments for endometriosis and contraceptives. However, whether Primodos caused birth defects or not remains controversial, and has been little investigated. Here we used the developing zebrafish embryo, a human cell-line and mouse retinal explants to investigate the actions of the components of Primodos upon embryonic and tissue development. We show that Norethisterone acetate and Ethinyl estradiol cause embryonic damage in a dose and time responsive manner. The damage occurs rapidly after drug exposure, affecting multiple organ systems. Moreover, we found that the Norethisterone acetate and Ethinyl estradiol mixture can affect nerve outgrowth and blood vessel patterning directly and accumulates in the forming embryo for at least 24 hrs. These data demonstrate that Norethisterone acetate and Ethinyl estradiol are potentially teratogenic, depending on dose and embryonic stage of development in the zebrafish. Further work in mammalian model species are now required to build on these findings and determine if placental embryos also are affected by synthetic sex hormones and their mechanisms of action.

Concepts: Pregnancy, Causality, Embryo, Developmental biology, Hormonal contraception, Affect, Mammal, Menstrual cycle

169

OBJECTIVE: To compare the effects of continuous use of oral (OC), transdermal, and vaginal combined contraceptives on the pituitary-ovarian axis and inhibition of follicular development. DESIGN: Spin-off study of a prospective, randomized trial. SETTING: University clinic. PATIENT(S): Forty-two of 54 healthy women completed the study. INTERVENTION(S): Treatment with combined OCs (ethinyl E(2) [EE] and desogestrel), transdermal patches (EE and norelgestromin), or vaginal rings (EE and etonogestrel) for 9 weeks continuously. Blood sampling was performed before and at 5 and 9 weeks of treatment. MAIN OUTCOME MEASURE(S): Changes in serum hormone levels induced by combined contraceptives. RESULT(S): Serum antimüllerian hormone (AMH), FSH, inhibin B, LH, and E(2) levels had decreased significantly in all study groups after 9 weeks of treatment. Significant declines were already detected after 5 weeks' use of combined contraceptives with regard to all hormone levels apart from those of serum AMH, where the decrease between baseline and 5 weeks was only moderate. Between groups, serum levels of AMH, inhibin B, LH, and E(2) were comparable at baseline and after 5 and 9 weeks of treatment. CONCLUSION(S): The decrease of serum AMH levels during the use of all combined contraceptives indicates that folliculogenesis is arrested independently of administration route. CLINICAL TRIAL REGISTRATION NUMBER: NCT01087879.

Concepts: Pharmacology, Sexual intercourse, Hormonal contraception, Transdermal patch, Contraceptive patch, Menstrual cycle, Route of administration, Follicular phase

168

In recent years there has been an explosion in the development of medical apps, with more than 40,000 apps now available. Nearly 100 apps allow women to track their fertility and menstrual cycles and can be used to avoid or achieve pregnancy. Apps offer a convenient way to track fertility biomarkers. However, only some use evidence-based fertility awareness-based methods (FABMs), which with ideal use have rates of effectiveness similar to those of commonly used forms of hormonal birth control. Since having a baby or preventing a pregnancy are important responsibilities, it is critical that women and couples have access to reliable, evidence-based apps that allow them to accurately track their fertility.

Concepts: Pregnancy, Birth control, Hormonal contraception, Combined oral contraceptive pill, Menstrual cycle, Progesterone, Implanon, Fertility awareness

168

Previous studies have demonstrated variable influences of sexual hormonal states on female brain activation and the necessity to control for these in neuroimaging studies. However, systematic investigations of these influences, particularly those of hormonal contraceptives as compared to the physiological menstrual cycle are scarce. In the present study, we investigated the hormonal modulation of neural correlates of erotic processing in a group of females under hormonal contraceptives (C group; N = 12), and a different group of females (nC group; N = 12) not taking contraceptives during their mid-follicular and mid-luteal phases of the cycle. We used functional magnetic resonance imaging to measure hemodynamic responses as an estimate of brain activation during three different experimental conditions of visual erotic stimulation: dynamic videos, static erotic pictures, and expectation of erotic pictures. Plasma estrogen and progesterone levels were assessed in all subjects. No strong hormonally modulating effect was detected upon more direct and explicit stimulation (viewing of videos or pictures) with significant activations in cortical and subcortical brain regions previously linked to erotic stimulation consistent across hormonal levels and stimulation type. Upon less direct and less explicit stimulation (expectation), activation patterns varied between the different hormonal conditions with various, predominantly frontal brain regions showing significant within- or between-group differences. Activation in the precentral gyrus during the follicular phase in the nC group was found elevated compared to the C group and positively correlated with estrogen levels. From the results we conclude that effects of hormonal influences on brain activation during erotic stimulation are weak if stimulation is direct and explicit but that female sexual hormones may modulate more subtle aspects of sexual arousal and behaviour as involved in sexual expectation. Results may provide a basis for future imaging studies on sexual processing in females, especially in the context of less explicit erotic stimulation.

Concepts: Hormonal contraception, Combined oral contraceptive pill, Magnetic resonance imaging, Cerebral cortex, Menstrual cycle, Endometrium, Progesterone, Ovulation