Contraceptive Options and Their Associated Estrogenic Environmental Loads: Relationships and Trade-Offs

<div><p>This work explores the relationships between a user's choice of a given contraceptive option and the load of steroidal estrogens that can be associated with that choice. Family planning data for the USA served as a basis for the analysis. The results showed that collectively the use of contraception in the USA conservatively averts the release of approximately 4.8 tonnes of estradiol equivalents to the environment. 35% of the estrogenic load released over the course of all experienced pregnancies events and 34% the estrogenic load represented by all resultant legacies are a result of contraception failure and the non-use of contraception. A scenario analysis conducted to explore the impacts of discontinuing the use of ethinylestradiol-based oral contraceptives revealed that this would not only result in a 1.7-fold increase in the estrogenic loading of the users, but the users would also be expected to experience undesired family planning outcomes at a rate that is 3.3 times higher. Additional scenario analyses in which ethinylestradiol-based oral contraceptive users were modeled as having switched entirely to the use of male condoms, diaphragms or copper IUDs suggested that whether a higher or lower estrogenic load can be associated with the switching population depends on the typical failure rates of the options adopted following discontinuation. And, finally, it was estimated that, in the USA, at most 13% of the annual estrogenic load can be averted by fully meeting the contraceptive needs of the population. Therefore, while the issue of estrogen impacts on the environment cannot be addressed solely by meeting the population's contraceptive needs, a significant fraction of the estrogenic mass released to environment can be averted by improving the level with which their contraceptive needs are met.</p></div

Relative contributions of intended (I) and unintended (U) pregnancy events to the total number of pregnancies, the estrogenic load released over the course of all pregnancies, and the estrogenic legacy represented by all resultant births.

<p>Refer to S7 to see how the various contributions were estimated.</p

Relationship between contraceptive choices and the resultant flows of steroidal estrogens (i.e., through direct excretion and contraceptive failure) contributing to the net load of steroidal estrogens attributed to the use of a particular contraceptive option (J_n) or the total of all options (i.e., ΣJ_n).

<p>Note that since mistimed births only lead to time-displaced estrogenic flows such pregnancies are not identified as a source of steroidal estrogenic attributable to a user's choice of a particular contraceptive option.</p

Estimated Steroidal Estrogen Loads in the USA circa 2002.

<p>The relative size of the pie charts is proportional to the logarithm of the estimated loads. Estrogen masses were estimated using the data compiled in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0092630#pone.0092630.s001" target="_blank">File S1</a>. Estradiol (E₂) equivalents were estimated by summing the respective mass loads of each estrogen, weighted according to their estrogenic potencies relative to estradiol, as follows: [E₁]/3+[E₂]+[E₃]/25+10·[EE₂]. The justifications for potencies weightings used in this equation are detailed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0092630#pone.0092630.s002" target="_blank">File S2</a>.</p

Additional file 2: of Frailty in end-stage renal disease: comparing patient, caregiver, and clinician perspectives

Binary variables utilized to construct Frailty Index. Listing of 32 binary variables utilized to construct the Frailty Index. (DOCX 21 kb

Additional file 1: of Perfusion by Arterial Spin labelling following Single dose Tadalafil In Small vessel disease (PASTIS): study protocol for a randomised controlled trial

SPIRIT 2013 checklist: recommended items to address in a clinical trial protocol and related documents. (DOC 120 kb

Perfusion by arterial spin labelling following single dose tadalafil in small vessel disease (PASTIS): study protocol for a randomised controlled trial

Background: Cerebral small vessel disease is a common cause of vascular cognitive impairment in older people, with no licensed treatment. Cerebral blood flow is reduced in small vessel disease. Tadalafil is a widely prescribed phosphodiesterase-5 inhibitor that increases blood flow in other vascular territories. The aim of this trial is to test the hypothesis that tadalafil increases cerebral blood flow in older people with small vessel disease. Methods/design: Perfusion by Arterial Spin labelling following Single dose Tadalafil In Small vessel disease (PASTIS) is a phase II randomised double-blind crossover trial. In two visits, 7-30 days apart, participants undergo arterial spin labelling to measure cerebral blood flow and a battery of cognitive tests, pre- and post-dosing with oral tadalafil (20 mg) or placebo. Sample size: 54 participants are required to detect a 15% increase in cerebral blood flow in subcortical white matter (p Discussion: Recruitment started on 4th September 2015 and 36 participants have completed to date (19th April 2017). No serious adverse events have occurred. All participants have been recruited from one centre, St George's University Hospitals NHS Foundation Trust. Trial registration: European Union Clinical Trials Register: EudraCT number 2015-001235-20 . Registered on 13 May 2015.</p