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 microg and levonorgestrel 100 microg) 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.     

Self-treatment patterns among adolescent girls with dysmenorrhea

STUDY OBJECTIVE: To describe both non-pharmacologic and pharmacologic treatments used by adolescents with dysmenorrhea. DESIGN: Cross-sectional study. SETTING: Urban academic medical center. PARTICIPANTS: Healthy adolescents aged 19 years or younger (n = 76) with moderate to severe primary dysmenorrhea were included; those using hormonal contraception were excluded. INTERVENTION: We collected baseline data via interview from adolescent girls at enrollment in a clinical trial of oral contraceptives versus placebo for primary dysmenorrhea. The interview data, collected prior to any intervention, included information on demographics, dysmenorrhea duration and severity, and self-treatment. We used the validated pain subscale of the Moos Menstrual Distress Questionnaire and a 0-10 pain rating scale to estimate pain severity. MAIN OUTCOME MEASURE: Investigator-administered questionnaire. RESULTS: Adolescents' mean age was 16.8 years (SD = 2). Similar proportions described themselves as white (26%), black (30%) or Hispanic (28%). Dysmenorrhea was moderate in 42%, severe in 58%, associated with nausea in 55%, and vomiting in 24%. Of those attending school (n = 66), 46% reported missing one or more days monthly due to dysmenorrhea. Nearly all discussed their pain with someone; however, a minority sought formal medical care. All used nonpharmacological remedies such as sleeping and heat application. Nearly all used at least one medication, 31% reported using two, and 15% used three medications (not concurrently). Many participants reported using medication at sub-therapeutic doses for pain. CONCLUSIONS: Adolescents with moderate and severe dysmenorrhea reported high morbidity. Girls used numerous non-pharmacologic remedies as well as medications for pain but infrequently accessed formal medical care. Medication dosing was often sub-therapeutic.     

Are combined oral contraceptives appropriate therapy for primary dysmenorrhea?

Current theories concerning the etiology of dysmenorrhea are reviewed, and the use of the combined oral contraceptive pill solely for dysmenorrhea is evaluated in light of the recent approval of antiprostaglandin agents for therapeutic use in relieving menstrual pain. Primary dysmenorrhea refers to menstrual cramping and discomfort in women free from underlying pathology and does not encompass symptoms occurring prior to the menses. There are many theories explaining the 2 types of dysmenorrhea, but none seems to offer a complete rationale. Current research appears to point toward a complex interaction of steroid hermones and prostaglandins. It is now accepted that although psychosocial factors are active in a woman's response to menstrual pain, they are not the cause. Oral contraceptives cannot be considered innocuous but have the potential for serious harm if casually prescribed and used. If a woman wants contraception concomitantly with seeking relief from severe dysmenorrhea, and if following a history and a physical she is found to be free of any pelvic pathology or contraindications for the oral contraceptive (OC), then OCs may be regarded as appropriate. There is now another choice of treatment available for dysmenorrhea -- ibuprofen -- if a woman does not need contraception or does not choose to use OC. The overall approach to care of a woman presenting with dysmenorrhea needs to be holistic. Now that there is an effective alternative in ibuprofen, continuous OC use solely for dysmenorrhea needs to be seriously questioned.     

Hair loss during treatment with oral contraceptives

Oral contraceptives with a dominant androgen component can cause or worsen androgen-dependent alopecia in women. This diagnosis can only be made if other causes of alopecia (which can occur at the same time as treatment with oral contraceptives) have been excluded. The patient's endocrine profile must be investigated sometimes, this being in order to detect any excess production of androgens. These types of alopecia call for the stopping of the oral contraceptive and sometimes also calls for oral anti-antigen treatment.     

Interactions with oral contraceptives

The interaction of a range of different factors with the pharmacologic activity of oral contraceptives is reviewed. Pharmacokinetic interactions with oral contraceptives may occur (1) during absorption and extrahepatic circulation, (2) by interfering with protein binding, and (3) during hepatic metabolism. The hepatic mixed function oxidase system, which is mainly responsible for the metabolism of oral contraceptives, is affected by several different factors and is easily induced. Nutrition affects the activity of many drugs, but information regarding oral contraceptives is meager. Both pharmacokinetic and pharmacodynamic interactions, which may be synergistic or antagonistic, between the estrogen and gestagen components of oral contraceptives, are important, but there is no correlation between the rate of metabolism of the two components. Evidence suggests that some anticonvulsant, antibiotic, and antibacterial drugs may reduce the efficacy of oral contraceptives. Instances of interactions of other therapeutic agents are reported infrequently. The incidence of serious interactions is low and does not appear to have been reduced with low-dose oral contraceptives, probably because of large intersubject variability in the pharmacokinetics of oral contraceptives.     

Effect of oral contraceptives containing estradiol and nomegestrol acetate or ethinyl-estradiol and chlormadinone acetate on primary dysmenorrhea

Abstract

Objective: To study the three cycles effect on primary dysmenorrhea of the monophasic 24/4 estradiol/nomegestrol acetate (E2/NOMAC) and of the 21/7 ethinyl-estradiol/chlormadinone acetate (EE/CMA) oral contraceptive. The tolerability and the effect of both preparations on metabolism and health-related quality of life were also evaluated.

Design: Prospective observational cohort study.

Setting: Tertiary gynecologic center for pelvic pain.

Patients: Subjects with primary dysmenorrhea requiring an oral contraceptive, who spontaneously selected either E2/NOMAC (n?=?20) or EE/CMA (n?=?20).

Main outcome measures: Visual Analogue Scale (VAS) score for dysmenorrhea, Short Form-36 questionnaire for health-related quality of life, lipoproteins and days of menstrual bleeding (withdrawal bleeding during oral contraceptive).

Results: Mean age and body mass index (BMI) were similar between the two groups. The final analysis was performed on 34 women, 15 in E2/NOMAC and 19 in EE/CMA group. Compliance with treatment was significantly higher with EE/CMA (100%) than E2/NOMAC (75%) (p?=?0.02). Both treatments significantly (p?<?0.0001) reduced VAS of primary dysmenorrhea, similarly (E2/NOMAC by a mean of 74.7%, EE/CMA by a mean of 78.4%; p?=?0.973). Only E2/NOMAC significantly increased SF-36 score (p?=?0.001), both in physical (p?=?0.001) and mental domains (p?=?0.004). The mean number of days of menstrual bleeding was significantly reduced in E2/NOMAC group (from 4.86?±?1.20?d to 2.64?±?1.59?d, p?=?0.0005 versus baseline, p?=?0.007 versus EE/CMA group). BMI did not vary in either group. E2/NOMAC did not change lipoproteins and apoproteins while EE/CMA increased total cholesterol (p?=?0.0114), HDL-cholesterol (p?=?0.0008), triglycerides (p?=?0.002), apoprotein-A1 (Apo-A1; p?=?0.0006) and apopoprotein-B (Apo-B; p?=?0.008), decreasing LDL/HDL ratio (p?=?0.024).

Conclusions: Both oral contraceptives reduced similarly primary dysmenorrhea, with E2/NOMAC also reducing withdrawal bleedings and being neutral on lipid metabolism.     

Drug interaction with oral contraceptives

As drug interaction can play a part in altering biological effectiveness of the administered agents, effective menstrual control by oral contraceptives may be jeopardized by simultaneous therapy with other drugs. And, conversely, oral contraceptives may alter the biotransformation of other therapeutic agents. The clinical literature concerning with drug induced contraceptive failure is still limited and apart from 1 or 2 exceptions consists of case reports generally on few patients. In a well-controlled study, Hempel and Klinger administered different psychotropic drugs to women taking 0.05 mg ethinyloestradiol plus 1.0 mg norethisterone acetate without menstrual dysfunction. Phenobarbitone and carbamazepine most frequently provoked bleeding disorders. It has been suggested that various anti-epileptic drugs will reduce the effectiveness of oral contraceptive steroids. Phenytoin administered experimentally to 14 women on oral contraceptives provoked bleeding disorders in 3. Janz and Schmidt refer to 3 patients becoming pregnant while on anti-epileptic drugs and oral contraceptives. Primidone, phenobarbitone and ethosuccimide were implicated. Gagnaire et al. and Belaish et al. cite individual cases of conception in patients treated with anti-epileptics including primidone given alone. Rifampicin is the antibiotic most clearly implicated in menstrual disorders and conception in women taking sequential or combined oral contraceptives. The main site of interaction of oral contraceptives with other drugs is in the liver where they share the same metabolising enzymes.