Doctors and overpopulation 48 years later: a second notice.

Overpopulation exacerbates environmental and health problems, from climate change to biodiversity loss and pandemics. It is the 'upstream' driver of numerous existential threats. Addressing this compassionately - always - should be axiomatic for doctors. Our profession, by dramatically reducing death-rates since the 1800s while birth-rates remained high, sadly bears - unintendedly - some responsibility for the increase: one billion then, eight billion looming. Therefore, as doctors, we must surely be uniquely motivated to: be involved in rights-based policies and services with unbroken supply chains ensuring optimal contraceptive care being available to all couples worldwide, remove well-known tangible (contraceptives unavailable) and intangible (cultural, religious and mis-informational) barriers to women's choice to access family planning everywhere, while achieving full gender equity, especially in education, warn how overpopulation risks all planetary life, through optimal environmental education both for colleagues and the public, and campaign for a maximum of two children (replacement fertility - or less) on principle. Doctors and Overpopulation was established in 1972. Before and since, this issue has become taboo, still affecting many doctors and even people claiming to care passionately about a sustainable future: the environmental NGOs. Their silence implies conservation goals are achievable regardless of human numbers, while many studies show they are not. It is time for an open discussion about this taboo. Therefore we, concerned doctors of 2020, reiterate here the doctors' 48-year long cri de Coeur.

The 7-day contraceptive hormone-free interval should be consigned to history.

AIM: This review summarises the available data on the disadvantages of the 7-day contraceptive-free interval (CFI) of combined oral contraceptives (COCs), in contrast to shorter CFIs or continuous use - including flexible regimens - and provides recommendations for practice. METHODS: Relevant papers were identified by Medline and PubMed. The final reference list was generated on the basis of relevance to the review, with priority given to systematic reviews and randomised controlled trials. RESULTS: There is considerable inter- and intra-individual variation in the absorption and metabolism of COCs. Even with perfect use, the loss of endocrine suppression during the standard 7-day CFI allows follicular development with the risk of escape ovulation in a vulnerable minority. This risk increases in typical users whenever the CFI is prolonged: late restarts are a common reason for pill omissions. Shortening or eliminating the CFI improves contraceptive efficacy using the lowest doses available, without evidence to date of compromised safety. CONCLUSIONS: There is no scientific evidence to support a 7-day CFI and it should be replaced either by a continuous flexible regimen, or extended regimens with a shortened CFI, prescribed first-line. In women preferring a monthly 'bleed', a 4-day CFI similarly provides a greater safety margin when pills are omitted.

Perspective on the role of P2X-purinoceptor activation in human vas deferens contractility.

The contractile actions of α,ß-methylene ATP (α,ß-meATP) and ATP and the effects of K(+) channel blockers in longitudinal and circular muscles of human vas deferens were investigated with a view to clarifying the functional importance of P2X(1)-purinoceptor activation and K(+) channels in modulating contractility of the tissues. The results provide an experiment-based perspective for resolving differing reports on purinergic activation of the tissues and uncertain roles of large-conductance Ca(2+)-activated K(+) (BK(Ca)) and voltage-gated delayed rectifier K(+) (K(V)) channels. α,ß-Methylene ATP (3-100 µm) evoked suramin-sensitive contractions of longitudinal muscle but rarely of circular muscle. ATP (0.1-3 mm) less reliably activated only longitudinal muscle contractions. These were enhanced by ARL 67156 (100 µm), but a different ectonucleotidase inhibitor, POM 1, was ineffective. Both muscle types were unresponsive to ADP-ßS (100 µm), a P2Y-purinoceptor agonist. Longitudinal muscle contractions in response to α,ß-meATP were enhanced by FPL 64176 (1 µm), an L-type Ca(2+) agonist, TEA (1 mm), a non-specific K(+) channel blocker, 4-aminopyridine (0.3 mm), a selective blocker of K(V) channels, and iberiotoxin (0.1 µm), a selective blocker of BK(Ca) channels. Quiescent circular muscles responded to α,ß-meATP reliably in the presence of FPL 64176 or iberiotoxin. Apamin (0.1 µm), a selective blocker of small conductance Ca(2+)-activated K(+) (SK(Ca)) channels had no effect in both muscle types. Y-27632 (1-10 µm) reduced longitudinal muscle contractions in response to α,ß-meATP, suggesting involvement of Rho-kinase-dependent contractile mechanisms. The results indicate that P2X(1)-purinoceptor stimulation elicits excitatory effects that: (a) lead to longitudinal muscle contraction and secondary activation of 4-aminopyridine-sensitive (K(V)) and iberiotoxin-sensitive (BK(Ca)) K(+) channels; and (b) are subcontractile in circular muscle due to ancillary activation of BK(Ca) channels. The novel finding of differential action by P2X(1)-purinoceptor agonists in the muscle types has functional implication in terms of the purinergic contribution to overall contractile function of human vas deferens. The modulatory effects of K(V) and BK(Ca) channels following P2X(1)-purinoceptor activation may be pivotal in providing the crucial physiological mechanism that ensures temporal co-ordination of longitudinal and circular muscle contractility.

Contraception for women taking antiepileptic drugs.

Antiepileptic drugs (AEDs) that induce hepatic enzyme activity may alter the metabolism of most hormonal methods of contraception, and this may affect their contraceptive efficacy. There is also the potential for the hormonal method to affect the AED. Women may also be prescribed AEDs to treat conditions other than epilepsy, such as chronic pain and migraine. These effects should be considered in the choice of both the treatment of the epilepsy and the choice of contraceptive method. This review considers these interactions and offers advice about their management.

A prospective cohort study of menstrual symptoms and morbidity over 15 years following laparoscopic Filshie clip sterilisation.

OBJECTIVE: To observe the incidence of menstrual symptoms and relevant surgery after sterilisation. STUDY DESIGN: 1101 women sterilised with Filshie clips between 1983 and 2002 were assessed prospectively comparing menstrual symptomatology documented immediately before surgery and 5-14 years later by questionnaire. MAIN OUTCOME MEASURES: Prevalence of menstrual dysfunction and subsequent surgery related to pre-operative menstrual symptoms and contraception. RESULTS: After excluding 232 (24%) of the 968 eligible women sent questionnaires whose address had changed, 573 of the remaining 735 women (78%) completed the questionnaire, 223 5-6 years after sterilisation, 175 after 7-9 years and 175 after 10-15 years; the respondents were demographically representative of the total population. Heavy periods increased from 9% before to 35% (P<0.0001) after sterilisation, painful periods from 2% to 21% (P<0.0001) and 6% had undergone hysterectomy or endometrial ablation. These findings were not influenced by the pre-sterilisation method of contraception but were inversely related to advancing age (P<0.0002). The lowest rates of menstrual symptoms were reported 10-15 years after sterilisation. CONCLUSION: Menstrual symptoms increased following Filshie clip sterilisation irrespective of pre-sterilisation symptoms and contraception. Whatever the causative mechanism, the progestogen-loaded intrauterine system (IUS), with similar efficacy but with improved menstrual symptoms, should be considered before sterilisation.

Contractile actions of L-type Ca2+ agonists in human vas deferens and effects of structurally different Ca2+ antagonists.

The actions of L-type Ca(2+) agonists, FPL 64176 and Bay K 8644 were investigated in human vas deferens in the presence of structurally different L-type Ca(2+) antagonists. The L-type Ca(2+) agonists (or=20 min) evoked only rhythmic contractility even in moderately depolarizing ([K(+)](o), 10mM) medium. These findings suggest low basal activity of L-type Ca(2+) channels (VOCs) in both muscle types. In the presence of L-type Ca(2+) agonists (1 microM), high [K(+)](o) (30 or 120 mM) evoked contractions with different profiles. Circular muscle had a predominance of rhythmic activity ([K(+)](o) 30 mM) and slow time to peak and decline ([K(+)](o) 120 mM). Longitudinal muscle was more tonic ([K(+)](o) 30 mM) with a rapid time to peak and decline ([K(+)](o) 120 mM). The contractions in both muscle types were blocked by nifedipine or methoxyverapamil; indicating the involvement of L-type VOCs and suggests that the distinct contractile profiles originate from differences in mechanisms that regulate contractility. In comparison to the conventional L-type Ca(2+) antagonists, fendiline, prenylamine and thioridazine were more effective against longitudinal than circular muscle contractions. Structurally similar diphenylalkylamines (cinnarizine, flunarizine, and pimozide) and phenothiazines (sulphoridazine, chlorpromazine, and trifluoperazine) inhibited the contractions comparably in both muscle types. These findings are discussed in relation to inhibition of muscle type-specific mechanisms that may contribute more to L-type VOC activation and contractility in longitudinal than in circular muscle.

Comparative effects of T-type and L-type Ca(2+)-antagonists against noradrenaline-induced contractions of human vas deferens.

OBJECTIVE: To investigate the effects of the relatively selective T-type Ca(2+)-antagonists, mibefradil and flunarizine, and the L-type Ca(2+)-antagonist, nifedipine, on the contractions of longitudinal and circular muscles of human vas deferens, to elucidate the possible involvement of T-type voltage-gated Ca(2+) channels (VOCs) in the contractile function of the tissue. MATERIALS AND METHODS: Human vas deferens specimens from elective vasectomies were cut into strips of longitudinal muscle or transversely into rings of circular muscle. These were set up for tension recording and superfused with Krebs' medium (36 degrees C). Contractions were evoked by noradrenaline or high [K(+)](o) (in the presence of the L-type Ca(2+) agonist, FPL 64176) and the effects of Ca(2+) antagonists were determined. RESULTS: Noradrenaline (0.1-100 micromol/L) evoked rhythmic and tonic contractions of longitudinal and circular muscles, which were potently inhibited by nifedipine (

Failure and regret after laparoscopic filshie clip sterilization under local anesthetic.

OBJECTIVE: To estimate the failure, regret, and reversal rates 5 or more years after laparoscopic Filshie clip sterilization using local anesthesia. METHODS: A total of 1,101 women underwent Filshie clip sterilization between 1983 and 2002. They completed follow-up questionnaires that were analyzed for the following outcomes: failed sterilization, regret after the operation, and sterilization reversal. RESULTS: Two hundred thirty-three of 968 (24%) eligible women sent the questionnaire had moved from their last known address. Of the remaining 735 women, 573 (78%) completed the questionnaire: 223 (39%) 5-6 years after the operation, 175 (30%) after 7-9 years, and 175 (30%) after 10-15 years. One pregnancy occurred 10 months after surgery, and one woman had the procedure repeated when unilateral tubal patency was identified by hysterosalpingography 3 weeks after surgery. Twenty-four (4%) women regretted having the operation; 7 (1.2%) women had a reversal operation, and all subsequently conceived. CONCLUSION: Failure after tubal sterilization using Filshie clips is less than 1:500 operations. Patient selection and surgeons' experience may have influenced these results. Regret occurred in a small proportion. LEVEL OF EVIDENCE: III.

The incidence of chronic scrotal pain after vasectomy: a prospective audit.

OBJECTIVE: To assess the extent of scrotal pain in men before and after vasectomy, to produce accurate data for the benefit of men considering this procedure, and hence improved informed consent about the outcomes, as chronic scrotal pain after vasectomy is a poorly quantified clinical problem. PATIENTS AND METHODS: Between November 2004 and January 2006 nine surgeons carried out vasectomies in 625 men (mean age 39.9 years, sd 5.6) under local anaesthesia. A questionnaire was devised to establish the presence of any scrotal or testicular pain, and to characterize this discomfort; 6 months after the procedure a modified version of the same questionnaire was administered. RESULTS: In all, 593 (94.7%) men returned the preoperative questionnaires and were entered into the study; 488 (82.2%) of these completed the follow-up questionnaire, giving a mean (sd) follow-up of 6.8 (1.6) months. In all, 65 men reported new-onset scrotal pain at 7 months (14.7%). The mean visual analogue score for this pain was 3.4/10. Four men (0.9%) in the responding group described pain after vasectomy as 'quite severe and noticeably affecting their quality of life'. CONCLUSION: At 7 months after vasectomy about 15% of previously asymptomatic men have some degree of scrotal discomfort. These early data indicate that chronic scrotal pain after vasectomy is a genuine entity, but a longer-term follow-up in this group will be important to allow further evaluation of how this pain develops with time.

Combined hormonal contraceptive trials: variable data collection and bleeding assessment methodologies influence study outcomes and physician perception.

Initially approved for use in the United States nearly 50 years ago, oral hormonal contraceptives containing both estrogen and progestin have undergone steady improvements in safety and convenience. Concurrent with improvements in safety associated with decreasing doses of both steroids, there has been an increased incidence of unscheduled bleeding and spotting. There exist no standards regarding data collection techniques and methods, and reporting and analysis of bleeding and spotting events during combined hormonal contraceptive (CHC) trials. For the regulatory review of hormonal contraceptives, data regarding the incidence of bleeding and spotting events are not included in either of the traditional categories of efficacy and safety. Standardization of methods for collecting and analyzing data about cycle control in all clinical trials of CHCs is long overdue. Until such standards are developed and implemented, clinicians need to familiarize themselves with the techniques used in each study in order to provide correct information to their patients about the frequency of bleeding and spotting associated with different formulations and delivery systems.

Recommendations for standardization of data collection and analysis of bleeding in combined hormone contraceptive trials.

This is the second of a two-article series describing the outcomes of the Hormonal Contraceptives Trial Methodology Consensus Conference held in Philadelphia, PA, on September 23, 2005. The first manuscript, "Hormonal Contraceptive Trials: Variable Data Collection and Bleeding Assessment Methodologies Influence Study Outcome and Physician Perception," provided a description of methodologies applied in the US Food and Drug Administration medical officer's review of clinical trial data as contained in the Summary Basis of Approvals of New Drug Applications, results of the review and general conclusions. This manuscript provides recommendations regarding best practices in trial design, data collection and analysis regarding bleeding data in combined hormone contraception trials.

Contraception for women with epilepsy.

Antiepileptic drugs that induce hepatic enzyme activity may alter the metabolism of most hormonal methods of contraception, and this affects the contraceptive regime. This effect should be considered in the choice of both the treatment of the epilepsy and the choice of contraceptive method. This review considers these interactions and offers advice about their management.