Anne R. Davis

Primary Dysmenorrhea in Adolescent Girls and Treatment with Oral Contraceptives

This review examines the prevalence, associated morbidity, and treatment of primary dysmenorrhea in adolescent girls. Relevant literature was examined by systematic, evidence-based review using MEDLINE and Cochrane Collaboration databases. Dysmenorrhea is highly prevalent during adolescence. Despite differences in measurement methods, 20%-90% of adolescent girls report dysmenorrhea and about 15% of adolescents describe their dysmenorrhea as severe. During adolescence, dysmenorrhea leads to high rates of school absence and activity nonparticipation. Most adolescents with dysmenorrhea self-medicate with over-the-counter preparations; few consult healthcare providers. Combined oral contraceptives (COC) are an accepted treatment for dysmenorrhea in nonadolescent women. However, data supporting the efficacy of COC is limited. Very small studies show decreased prostaglandin in menstrual fluid associated with high-dose COC use. Larger studies are limited to cross-sectional comparisons showing lower prevalence of dysmenorrhea in low-dose COC users compared to non-COC users. One small, randomized controlled trial including some adolescents demonstrated an improvement in dysmenorrhea with high-dose COC treatment compared to placebo. The efficacy of low-dose COC in the treatment of adolescent dysmenorrhea has yet to be determined. If effective, well-established safety and noncontraceptive health benefits may make COC an ideal treatment for dysmenorrhea in adolescent girls.

Accelerated High-Yield Generation of Limb-Innervating Motor Neurons from Human Stem Cells

Human pluripotent stem cells are a promising source of differentiated cells for developmental studies, cell transplantation, disease modeling, and drug testing. However, their widespread use even for intensely studied cell types like spinal motor neurons is hindered by the long duration and low yields of existing protocols for in vitro differentiation and by the molecular heterogeneity of the populations generated. We report a combination of small molecules that within 3 weeks induce motor neurons at up to 50% abundance and with defined subtype identities of relevance to neurodegenerative disease. Despite their accelerated differentiation, motor neurons expressed combinations of HB9, ISL1, and column-specific markers that mirror those observed in vivo in human embryonic spinal cord. They also exhibited spontaneous and induced activity, and projected axons toward muscles when grafted into developing chick spinal cord. Strikingly, this novel protocol preferentially generates motor neurons expressing markers of limb-innervating lateral motor column motor neurons (FOXP1+/LHX3−). Access to high-yield cultures of human limb-innervating motor neuron subtypes will facilitate in-depth study of motor neuron subtype-specific properties, disease modeling, and development of large-scale cell-based screening assays.

Oral contraceptives for dysmenorrhea in adolescent girls. A randomized trial.

Objective: To assess whether a low-dose oral contraceptive (OC) is more effective than placebo treatment for dysmenorrhea pain in adolescents. Methods: This was a randomized, double-blind, placebo-controlled clinical trial of 76 healthy adolescents aged 19 years or younger reporting moderate or severe dysmenorrhea. Subjects were randomly allocated to receive either an OC (ethinyl estradiol [E2] 20 &mgr;g and levonorgestrel 100 &mgr;g) or a matching placebo for 3 months. Participants used their usual pain medications as needed during the trial. The main outcome measure was score on the Moos Menstrual Distress Questionnaire (pain subscale) for the third menstrual cycle on treatment. Secondary outcomes included pain intensity (rated 0 to 10), days of any pain, days of severe pain, hours of pain on worst day, and use of pain medications. Results: The mean Moos Menstrual Distress Questionnaire pain score was lower (less pain) in the OC group than the placebo group (3.1, standard deviation 3.2 compared with 5.8, standard deviation 4.5, P = .004, 95% confidence interval for the difference between means 0.88–4.53). By cycle 3, OC users rated their worst pain as less (mean pain rating 3.7 compared with 5.4, P = .02) and used fewer pain medications than placebo users (mean pain pills used 1.3 compared with 3.7, P = .05). By cycle 3, OC users reported fewer days of any pain, fewer days of severe pain, and fewer hours of pain on the worst pain day than placebo users; however, these differences did not reach statistical significance. Conclusions: Among adolescents, a low-dose oral contraceptive relieved dysmenorrhea-associated pain more effectively than placebo. Level of Evidence: I

Tubal sterilization: focus on the U.S. experience

OBJECTIVE To review the frequency, effectiveness, and clinical sequelae of tubal sterilization with a focus on the U.S. experience. DESIGN A review of U.S. health care statistics and English-language literature using a MEDLINE search, bibliographies of key references, and U.S. government publications. PATIENT(S) Women seeking tubal sterilization. INTERVENTION Tubal sterilization. MAIN OUTCOME MEASURE(S) Effectiveness and long-term risks and benefits. RESULT(S) Half of the 700,000 annual bilateral tubal sterilizations (TS) are performed postpartum and half as ambulatory interval procedures. Eleven million U.S. women 15-44 years of age rely on TS for contraception. Failure rates vary by method with one third or more resulting in ectopic pregnancy. Reversal is most successful after use of methods that destroy the least tube. Evidence of menstrual or hormonal disturbance after TS is weak, although some studies find higher rates of hysterectomy among previously sterilized women. Decreased risk of subsequent ovarian cancer has been observed among sterilized women. CONCLUSION(S) Tubal sterilization is highly effective and safe. Failures, although uncommon, occur at higher rates than previously appreciated. Evidence for hormonal or menstrual changes due to TS is weak. Tubal sterilization is associated with decreased risk of ovarian cancer.

Oral Contraceptives and Libido in Women

Abstract Oral contraceptives (OCs) provide safe, effective, and reversible contraception and are widely used by women for fertility control. Little is known about the effects of OCs on sexual functioning. This paper critically examines the published literature addressing the impact of OCs on sexual desire or libido. We reviewed 30 original research studies. In the retrospective, uncontrolled studies (n = 17), it was found that most women reported an increase in libido during OC use. In the uncontrolled, prospective studies (n = 4), it was found that most women reported little change in libido during OC use. In the prospective and cross-sectional controlled studies (n = 4), women using OCs reported both increased and decreased libido compared to non-OC users. The findings from randomized, placebo-controlled studies (n = 5) were mixed: In the most recent and well-conducted trial, a decrease in libido in OC users compared to placebo users was found. Overall, women experience positive effects, negative effects, as well as no effect on libido during OC use. Better-designed studies are needed to establish the independent, causal effects of OCs on libido.

Reproductive history, sexual behavior and use of contraception in women with epilepsy

BACKGROUND Women with epilepsy experience more pregnancy-related risks than do their healthy peers. Guidelines recommend highly effective contraception. However, their contraceptive practices remain unknown. STUDY DESIGN We conducted a cross-sectional questionnaire study among reproductive-age women (18-44 years) with epilepsy presenting for routine, outpatient visits to an urban, academic medical center. Our questionnaire, in English or Spanish, included demographic characteristics, reproductive history, antiepileptic drug use, sexual behavior and contraception. RESULTS Participants had a mean age of 32 years (S.D.=8), 32% spoke Spanish and described themselves as Hispanic. Participants reported a wide range of educational attainment, insurance payor and income. About half of the participants reported at least one pregnancy, and 50% of the 181 pregnancies reported were unplanned. Among the 53% who reported intercourse in the last month, 74% used contraception, 15% were pregnant, 5% did not want to use contraception, 3% sought pregnancy and 3% had hysterectomy. Of those using contraception, 53% used highly effective methods (sterilization, intrauterine device, hormonal pill, patch and injection), and 47% used less effective methods (condom, withdrawal, rhythm and spermicide). Among the 21 participants using hormonal methods, six concomitantly took enzyme-inducing antiepileptic drugs potentially increasing susceptibility to pregnancy. DISCUSSION In this sample of women with epilepsy about half reported prior pregnancies; 50% were unplanned. Of those using contraception, only 53% used a highly effective method. Future studies should determine generalizability of these findings and explore reasons for inadequate family planning in women with epilepsy.

Intracervical lidocaine gel for intrauterine device insertion: a randomized controlled trial

BACKGROUND Pain during intrauterine device (IUD) insertion can be a barrier to initiation. Clinical trials have found misoprostol and nonsteroidal drugs to be ineffective (Am J Obstet Gynecol 2006;195:1272-1277, Hum Reprod 2011;26:323-329, Hum Reprod 2007;22:2647-2652). One study suggested that 2% lidocaine gel decreased pain; however, study design problems limit its validity (Brit J Fam Plann 1996;22:177-180). We tested whether intracervical 2% lidocaine gel decreased insertion pain compared to placebo. STUDY DESIGN We planned a randomized, double-blinded clinical trial of 200 women. We placed 2% lidocaine gel or placebo in the cervix prior to uterine sounding. Participants rated pain by marking a 100-mm visual analogue scale at four time points. RESULTS We randomized 200 participants and placed 197 IUDs. Pain was greatest at uterine sounding and similar between groups: placebo group mean 51.6 mm (SD 25), lidocaine group mean 55.5 mm (SD 30, p=.33). Stratified analyses accounting for parity showed no treatment effect. Multivariable analyses identified longer time since last pregnancy, lower parity and higher anticipated pain as predictors of pain during sounding, and dysmenorrhea and the levonorgestrel IUD as additional predictors during IUD insertion. CONCLUSIONS Intracervical 2% lidocaine gel does not decrease IUD insertion pain. Understanding predictors of increased pain may help providers with preprocedure counseling.

The epidemiology and definition of female sexual disorders

Abstract. Female sexual dysfunction (FSD) is a multifactorial condition that has anatomical, physiological, medical, psychological, and social components. Similar to erectile dysfunction in men, FSD is highly prevalent and often undertreated. Due to the development of successful treatment for male erectile dysfunction, FSD is receiving increased attention. Only a few studies dealing with epidemiology of female sexual dysfunction are available in the literature. However, research efforts in the field are increasing. This overview presents currently used classification systems, recently updated definitions, as well as prevalence data on the different entities of female sexual disorders.

Carbamazepine coadministration with an oral contraceptive: Effects on steroid pharmacokinetics, ovulation, and bleeding

Purpose:  Antiepileptic drugs (AEDs) are widely used in reproductive‐age women. The AED carbamazepine (CBZ) induces the hepatic cytochrome P450 system, thereby accelerating hormone metabolism. We sought to assess the pharmacodynamic effects of CBZ on breakthrough bleeding and ovulation during oral contraceptive (OC) use.

Timing of copper intrauterine device insertion after medical abortion: a randomized controlled trial.

OBJECTIVE: To compare intrauterine device (IUD) use at 6 months in women randomized to receive an intrauterine copper contraceptive 1 week compared with 1 month after medical abortion. METHODS: We recruited women undergoing medical abortion with mifepristone and misoprostol and choosing the copper IUD for contraception. We randomly assigned participants to “immediate” insertion 1 week after mifepristone or “delayed” insertion 4–6 weeks later. We followed rates of IUD insertion, 6-month utilization, expulsion, removal, and pregnancy. Participants recorded bleeding in a diary for 4 weeks. RESULTS: We randomized 156 participants. We inserted an IUD in 97% of participants in the immediate group and 76% in the delayed group (P<.001). At 6 months, 69% of participants in the immediate group used the IUD compared with 60% in the delayed group (P=.24). Expulsion rates were comparable; 12% (8 of 69) in the immediate group compared with 11% (7 of 65) in the delayed group. Removals occurred in 14% (10 of 69) of immediate and 8% (5 of 65) of delayed group participants (P=.21). Four pregnancies occurred in delayed group participants who did not return for IUD insertion (P=.09). The immediate and delayed groups reported a median of 20 and 19 bleeding or spotting days, respectively (P=.15). We detected no cases of serious infection, uterine perforation, or hemorrhage. CONCLUSION: Immediate insertion increased uptake of the IUD without increasing expulsions or bleeding. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, www.clinialtrials.gov, NCT00737178. LEVEL OF EVIDENCE: I