Oral Contraceptive Cycle Research Articles

Comparison of human-derived menotropin versus recombinant follicle stimulating hormone in in vitro fertilization cycles utilizing GnRH antagonist

Background: Although many studies have been published comparing hMG to rFSH with a GnRH agonist, information is lacking for similar comparisons using a GnRH antagonist.Objective: To test the null hypothesis that IVF/ET cycle performance parameters and success are not significantly different between patients administered a GnRH antagonist and either hMG or rFSH for ovarian stimulation.Materials & Methods: A retrospective cohort study of consecutively treated infertile reproductive aged women presenting to a private fertility practice for IVF/ET. Induction protocols consisted of a single cycle of oral contraceptives followed by a cycle day 3 start of either hMG (Repronex, Ferring) or rFSH (Gonal-F, Serono), each combined with a midfollicular phase start GnRH antagonist. Patient demographics, cycle performance characteristics, numbers of oocytes and embryos and live birth rates were examined.Results: During the 18 months examined, a total of 206 patients were identified to have cycled on either hMG (114) or rFSH (92). Mean patient age, BMI, indications for IVF/ET, cycle day 3 FSH levels and semen parameters did not differ significantly between the two groups (p>0.05). Length of induction, amount of medication administered, and peak estradiol levels were likewise similar (p>0.05). Mean numbers of oocytes retrieved, fertilization rates, and numbers of embryos transferred were the same (p>0.05). Live birth rates did favor hMG over rFSH patients (43% vs. 28%, respectively p<0.05). This advantage was seen across all age groups.Serum LH levels were significantly lower among rFSH patients on the day following antagonist administration compared to hMG recipients (p<0.05). Furthermore, this dramatic drop in LH levels among rFSH patients was strongly associated with IVF failure.Conclusion: IVF patients receiving hMG + GnRH antagonist demonstrate higher live birth rates compared to those receiving rFSH + GnRH antagonist. This difference could not be attributed to patient selection, demographics, cycle response or in vitro gamete performance. The observed difference reflects the efficiency of the GnRH antagonist’s suppression of endogenous LH in combination with the absolute lack of an exogenous LH source by rFSH, causing LH levels to fall below a critical threshold. We therefore reject the null hypothesis and report a superior outcome of hMG over rFSH when utilizing a GnRH antagonist for induction in IVF/ET. Background: Although many studies have been published comparing hMG to rFSH with a GnRH agonist, information is lacking for similar comparisons using a GnRH antagonist. Objective: To test the null hypothesis that IVF/ET cycle performance parameters and success are not significantly different between patients administered a GnRH antagonist and either hMG or rFSH for ovarian stimulation. Materials & Methods: A retrospective cohort study of consecutively treated infertile reproductive aged women presenting to a private fertility practice for IVF/ET. Induction protocols consisted of a single cycle of oral contraceptives followed by a cycle day 3 start of either hMG (Repronex, Ferring) or rFSH (Gonal-F, Serono), each combined with a midfollicular phase start GnRH antagonist. Patient demographics, cycle performance characteristics, numbers of oocytes and embryos and live birth rates were examined. Results: During the 18 months examined, a total of 206 patients were identified to have cycled on either hMG (114) or rFSH (92). Mean patient age, BMI, indications for IVF/ET, cycle day 3 FSH levels and semen parameters did not differ significantly between the two groups (p>0.05). Length of induction, amount of medication administered, and peak estradiol levels were likewise similar (p>0.05). Mean numbers of oocytes retrieved, fertilization rates, and numbers of embryos transferred were the same (p>0.05). Live birth rates did favor hMG over rFSH patients (43% vs. 28%, respectively p<0.05). This advantage was seen across all age groups. Serum LH levels were significantly lower among rFSH patients on the day following antagonist administration compared to hMG recipients (p<0.05). Furthermore, this dramatic drop in LH levels among rFSH patients was strongly associated with IVF failure. Conclusion: IVF patients receiving hMG + GnRH antagonist demonstrate higher live birth rates compared to those receiving rFSH + GnRH antagonist. This difference could not be attributed to patient selection, demographics, cycle response or in vitro gamete performance. The observed difference reflects the efficiency of the GnRH antagonist’s suppression of endogenous LH in combination with the absolute lack of an exogenous LH source by rFSH, causing LH levels to fall below a critical threshold. We therefore reject the null hypothesis and report a superior outcome of hMG over rFSH when utilizing a GnRH antagonist for induction in IVF/ET.

Measuring performance during the menstrual cycle: a model using oral contraceptives.

The aim of the study was to use a low-dose oral contraceptive (OC) pill to generate consistent estrogen and progestogen concentrations and investigate the relationship between steroid hormone concentrations during the OC cycle and anaerobic performance. Five female rowers taking a low-dose OC performed tests of anaerobic power (10-s all-out effort) and capacity (1000-m row) on the Concept IIC rowing ergometer at two time points in each of three OC cycles. These time points corresponded to high estrogen and high progestogen (pill day 16-18; TDH) and low estrogen and low progestogen (pill day 26-28; TDL). Blood samples were collected at rest and postexercise for the quantification of 17beta-estradiol (E2), progesterone (P4), glucose, triglyceride, and lactate concentrations. Endogenous E2 and P4 concentrations were not significantly different between testing days or OC cycles (P > 0.05). Peak power output was higher (P < 0.05) and 1000-m rowing ergometer time faster (P < 0.05) at TDL. Pre- and postexercise glucose concentrations were increased (P < 0.05) at TDL, whereas rest and postexercise plasma triglyceride concentrations were significantly (P < 0.05) lower during this time. This study found that alterations in anaerobic performance throughout the OC cycle occurred with improved performances corresponding to low estrogen and progestogen concentrations. The OC provided a consistent hormonal milieu reducing inter- and intra-individual variations in sex steroids and standardized all performance and metabolic variables across each OC cycle tested. Given that OC use has a high prevalence among female athletes and provides a controlled hormonal environment, it serves as a good model in which the acute effects of female sex steroids on exercise performance can be studied.

Long-Cycle Treatment with Oral Contraceptives

The conventional regimen of oral contraceptive (OC) use mimics the natural cycles by causing regular withdrawal bleeding, which can be avoided by omission of the hormone-free interval of 7 days. Consequently, long-cycle regimens with continuous administration of OCs for 3 or 6 months followed by a hormone-free interval of 7 days may reduce the frequency of menstruations and cycle-dependent complaints. Surveys have revealed that, despite a higher rate of irregular bleeding, the majority of women prefer the long-cycle regimen to the conventional OC regimen with regular bleeds every 4 weeks because it may improve quality of life. As this regimen increases the contraceptive efficacy to a large degree, continuous treatment with OCs may prevent unintended pregnancies in women who miss a pill or are concomitantly treated with drugs that are able to impair the efficacy of OCs. Postponement of withdrawal bleeding may also reduce or prevent menses-associated disorders such as hypermenorrhoea and dysmenorrhoea, and have beneficial effects in patients with haemorrhagic diathesis, endometriosis, uterine leiomyoma and polycystic ovary syndrome. Continuous use of OCs prevents the cyclic fluctuations of serum levels of ethinylestradiol and progestogen and, hence, the cyclic variations of metabolic serum parameters. Although the long-cycle regimen is initially associated with an elevated rate of irregular bleeding, the total number of bleeding days that require sanitary product protection is lower than during conventional OC treatment. Many physicians tend to prescribe extended OC cycles for postponement of menstruation or reduction of frequency of regular bleeding. This review summarises and examines the available data on OC long-cycle regimens. The data suggest that the rate of treatment-related side effects with OCs according to the long-cycle regimen is similar to that of conventional OC regimens. However, clinical trials are necessary to assess the impact of long-term OC long cycles on safety, particularly the risk of cancer and cardiovascular disease, and fertility after discontinuation of treatment.

Continuous use of an oral contraceptive for endometriosis-associated recurrent dysmenorrhea that does not respond to a cyclic pill regimen

Objective To ascertain whether long-term reduction of pain is obtained by continuous administration of an oral contraceptive (OC) in women with endometriosis-associated recurrent dysmenorrhea that does not respond to cyclic OC use. Design Prospective, therapeutic, self-controlled clinical trial. Setting A tertiary care and referral center for patients with endometriosis. Patient(s) Fifty women who underwent surgery for endometriosis in the previous year and experienced recurrent dysmenorrhea despite cyclic OC use. Intervention(s) Continuous use of an OC containing ethinyl estradiol (0.02 mg) and desogestrel (0.15 mg) for 2 years. Main outcome measure(s) Dysmenorrhea variation during cyclic and continuous OC use, evaluated with a 100-mm visual analog scale and a 0- to 3-point verbal rating scale, and degree of satisfaction with continuous OC treatment. Result(s) In the study period, amenorrhea, spotting, and breakthrough bleeding were reported by 19 (38%), 18 (36%), and 13 (26%) women. The mean ± SD number of >7-day bleeding episodes with consequent 7-day OC suspension was 5.5 ± 2.1. The mean ± SD dysmenorrhea visual analog scale and verbal rating scale scores were 75 ± 13 and 2.4 ± 0.5 at baseline and 31 ± 17 and 0.7 ± 0.6 at 2-year follow-up, respectively. Moderate or severe side effects were reported by 7/50 (14%) women. At final evaluation, 13 (26%) women were very satisfied, 27 (54%) were satisfied, 1 (2%) was uncertain, 8 (16%) were dissatisfied, and 1 (2%) was very dissatisfied. Conclusion(s) Long-term continuous OC use can be proposed to women with symptomatic endometriosis and menstruation-related pain symptoms.

Oral contraceptive treatment in polycystic ovarian syndrome improves mental health

Objective: The primary objective of this study was to derive preliminary data concerning the effect of oral contraceptive (OC) therapy on mental health measures in women with polycystic ovarian syndrome (PCOS). Design: This is an interim data analyses at 24 weeks from a treatment trial that will continue for 48 weeks. Evaluations were performed at baseline and after 24 weeks of therapy. We also assessed a control sample at baseline to establish differences on variables of interest. Materials and Methods: Twelve women (M age = 24) with PCOS, identified by means of elevated free androgen levels, oligomenorrhea, and hirsutism, completed the treatment intervention. Six healthy women (M age = 31), who were normally cycling, also were assessed during the early follicular phase of the menstrual cycle for baseline comparisons only. The pre-treatment baseline and 24-week studies included indices of androgen level, PCOS-related physical signs, general and PCOS-specific emotional symptoms, and measures of cognitive function. The treated women received either continuous or cyclic OC therapy with Loestrin (norethindrone acetate, 1 mg plus ethinyl estradiol, 20 mcg). Results: At baseline, there was no difference between the treatment group and the control group with respect to IQ estimate (t = 1.21, ns) or verbal memory function (t = 1.72, ns). However, as might be expected, there were significant differences between treatment subjects and controls with respect to free androgen levels (t = 2.43, p < .03) and measures of mood disturbance (t = 2.22, p < .05) and self esteem (t = 2.01, p < .05). After 24 weeks of Loestrin treatment, subjects showed significantly decreased free androgen levels as compared with baseline (t = 2.69, p < .03). In addition, all PCOS-specific symptoms and general measures of psychological well-being showed change in the positive direction. Tests for dependent measures indicated improvement in emotional symptoms (t = 3.85, p < .01), perception of bodily hair (t = 3.63, p < .01), weight concern (t = 3.73, p < .01), and menstrual concern (t = 3.32, p < .01). There also was improvement in overall self esteem (t = 2.61, p< .05) and a trend for improvement in total mood disturbance (t = 1.87, p < .10). Finally, there was marked improvement in delayed recall on a verbal memory task (t = 3.94, p < .003). Conclusion: These findings are encouraging with respect to improvement in multiple aspects of psychological well being in concert with treatment producing hormonal regulation and diminished physical features of PCOS. The improvements in mood and self-esteem might be understood most readily as psychological responses to the changes in the physically apparent signs of androgen irregularity. There also may be psychological effects mediated by direct neural actions of the hormone intervention, and the improvement in verbal memory function may reflect this effect. These interim results justify continued investigation of the mental health effects of PCOS treatment. In particular, randomized, controlled interventions would be useful in understanding the nature of psychological change associated with treatment and to compare continuous and cyclic forms of therapy.

Continuous combination oral contraceptive pills to eliminate withdrawal bleeding: a randomized trial

Objective To compare bleeding profiles of a traditional 28-day oral contraceptive pill cycle with continuous administration. Methods After a 28-day run-in cycle, women were randomized to either 28-day cycles (21 active pills and a pill-free week) or continuous use of the same 20-μg ethinyl estradiol/100-μg levonorgestrel formulation for 12 study cycles (336 days). The number of bleeding and spotting days were measured by daily diary. A subset underwent cycle 1 ( n = 16), and nine ( n = 14) pelvic ultrasound and endometrial histology sampling. Blood pressure, weight, hemoglobin, and adverse events were measured at revisit. The sample size with 80% power to detect a 67% reduction in bleeding days required 27 subjects in each arm. Results Of the 79 subjects randomized, 28 (70%) of the 28-day cycle and 32 (82%) of the continuous-use subjects completed the entire study ( P = .6). With continuous use, 49%, 68%, and 88% of women reported no bleeding during cycles 2, 6, and 12, respectively. Amenorrhea or infrequent bleeding was present in 68% of continuous users during cycles 1–3 and increased to 88% during cycles 10–12. Spotting during cycle days 1–21 increased initially with continuous use but reduced over time, and by 9 months was less than the spotting reported by cyclic users. Adverse events, blood pressure, weight, and hemoglobin findings were similar between groups. Conclusion Extension of the 28-day oral contraceptive cycle to continuous use with a low-estrogen dose combination oral birth control pill resulted in significantly fewer bleeding days.

Sleep in women across the life cycle from adulthood through menopause.

Studies of sleep across the life cycle in women have utilized both survey and polysomnographic techniques, but have tended to be of small sample size with diverse methodology. As a result, definitive conclusions about the impact of the menstrual cycle and use of oral contraceptives on sleep parameters cannot yet be made. Sleep disruption during pregnancy and postpartum is nearly universal, but effective and practical countermeasures are still needed. Longitudinal studies of sleep in the postpartum period are also lacking. Menopause is associated with insomnia due to several factors including hot flashes, mood disorders and increased sleep-disordered breathing. The use of hormone replacement therapy to treat sleep and other variables is an active area of investigation. In summary, much research is required to fully elucidate the impact of the life cycle on sleep parameters in women.

Estrogen fluctuations, oral contraceptives and borderline personality

Results from three studies suggest fluctuation in estrogen level may influence the expression of borderline personality disorder (BPD) symptoms. In the first study, 226 women were administered the Personality Assessment Inventory, borderline scales (PAI-BOR; L.C. Morey, The Personality Assessment Inventory, Professional Manual, 1991) and a questionnaire that assessed time in menstrual cycle and use of oral contraceptives, that is synthetic estrogens. BPD symptoms were most common in women using oral contraceptives and during times in the menstrual cycle when estrogen level is rising. In Study 2, 52 women were measured four times across one menstrual cycle and provided salivary samples at each test session. The samples were assayed and estrogen levels were obtained. The principle finding was that variation in estrogen levels predicted the presence of BPD symptoms ( r=0.4, p<0.01). This relationship remained significant when a general increase in negative affect was statistically controlled. Study 3 employed a pre–post Oral Contraceptive (OC) design with a control group. It was found that for women with high pre-existing levels of BPD, symptoms became significantly worse after starting pill use ( F (3,42)=4.7; p<0.01). Research findings that link the serotonin system and estrogen are reviewed and theoretical and practical implications are discussed.

Effects of the oral contraceptive pill cycle on physiological responses to hypoxic exercise.

To test whether the oral contraceptive pill cycle affects endocrine and metabolic responses to hypoxic (fraction of inspired oxygen = 13%, P(IO2): 95 mmHg; H) versus normoxic (P(IO2):153 mmHg; N) exercise, we examined eight women (28 +/- 1.2 yr) during the third (PILL) and placebo (PLA) weeks of their monthly oral contraceptive pill cycle. Cardiopulmonary, metabolic, and neuroendocrine measurements were taken before, during, and after three 5-min consecutive workloads at 30%, 45%, and 60% of normoxic V(O2peak) in H and N trials. Heart rate response to exercise was greater in H versus N, but was not different between PILL and PLA. Lactate levels were significantly greater during exercise, and both lactate and glucose levels were significantly greater for 30 min after exercise in H versus N (p < 0.0001). When expressed relative to baseline, lactate levels were lower in PILL versus PLA, but glucose was greater in PILL versus PLA (p < 0.001). Cortisol levels were also significantly greater in PILL versus PLA (p < 0.001). Norepinephrine levels were significantly increased during exercise (p < 0.0001) and in H versus N (p < 0.0001). However, epinephrine levels were not different over time or with trial. Thus, the presence of circulating estradiol and progesterone during the PILL phase reduces glucose and lactate responses to hypoxic exercise.

Management of ovarian endometriomas.

The efficiency of medical therapy as a unique treatment for endometrioma has not been demonstrated. Operative laparoscopic management is the 'gold standard' for surgical treatment, and there are no indications to prescribe medical treatment before cystectomy. Post-operative administration of low-dose cyclic oral contraceptives does not significantly affect the long-term recurrence of endometriosis after surgical treatment. In case of infertility, the management of endometriomas is controversial. Recurrent ovarian surgery is not recommended.

Hormonal pregnancy test redux

Given the large numbers of women affected and the risks inherent in pregnancy and childbirth in the countries where they live amenorrheic women presenting for contraception beyond 6 months post-partum need a new option. If pregnancy cannot be excluded by pregnancy test or by history (e.g. by determining that the woman has not had unprotected intercourse since delivery) we propose initiating one full cycle of combined oral contraceptives (COCs) immediately. This approach has two benefits: it provides effective contraception to the client and in addition it can serve as a pregnancy test. At the end of 21 days the woman would cease taking active pills for a week as usual. Bleeding at that time would indicate no pregnancy and the woman could continue COCs or switch to a different method. Lack of bleeding would indicate a possible pregnancy and the woman would be instructed to stop taking thepills and seek a pregnancy test. She could also be counseled ahead of time about where to seek prenatal care or other options. (excerpt)

Continuous use of oral contraceptive (OC) for endometriosis-associated recurrent dysmenorrhea not responding to cyclic pill regimen

Objective: To ascertain whether a long-term reduction of pain and an appreciable degree of overall satisfaction with therapy are obtained by administering a low-dose, monophasic OC continuously in women with endometriosis-associated recurrent dysmenorrhea not responding to cyclic OC use.

Menstrual reduction with extended use of combination oral contraceptive pills: randomized controlled trial

OBJECTIVE: To compare a traditional 28-day cycle to an extended 49-day cycle of the 30 μg ethinyl estradiol (E2)/300 μg norgestrel monophasic birth control pill regimen. METHODS: Ninety subjects randomized to either 28-day cycles with 21 active pills or 49-day cycles with 42 active pills for a prospective open label trial over four 84-day reference periods or trimesters. Bleeding, pill taking, and symptom diaries were completed. The sample size with 80% power to detect a 40% reduction in bleeding days required 24 subjects in each arm. RESULTS: Of the 90 women, 24 subjects (54.5%) on the 28-day cycle and 29 (63%) on the 49-day cycle completed the entire study ( P = .41). There were no statistically significant differences between the two groups in demographics or continuation rates. There was a significant reduction in bleeding days in the experimental arm beginning in the first trimester (28-day = 10.9, 49-day = 6.4 mean days of bleeding, P < .001) and continuing to the fourth trimester (28-day = 11.3, 49-day = 5.8 mean days, P = .005). The number of spotting days was similar between both schedules in the first trimester (28-day = 4.8, 49-day = 3.7 mean days, P = .24) and continued into the fourth trimester (28-day = 3.4, 49-day = 2.9 mean days, P = .30). Annual expenditure for hygiene products was significantly less for extended use subjects (28-day = $41.45, 49-day = $17.54 spent, P < .001). CONCLUSION: Extension of the 28-day oral contraceptive (OC) cycle to a 49-day cycle resulted in fewer bleeding days and no increase in mean spotting days or bleeding episodes.

Postoperative administration of monophasic combined oral contraceptives after laparoscopic treatment of ovarian endometriomas: A prospective, randomized trial

Objective: We sought to evaluate the efficacy of postoperative administration of monophasic, combined, low-dose oral contraceptives on endometrioma recurrence and on persistence-recurrence of associated pain symptoms after laparoscopic treatment of moderate-to-severe endometriosis. Study Design: In a prospective, randomized trial 70 patients who were not attempting to conceive, aged 20 to 35 years, underwent laparoscopic excision of ovarian endometriomas, followed by either postoperative administration of low-dose cyclic oral contraceptives for 6 months or no treatment on the basis of a computer-generated sequence. At 3 and 6 months after surgery and then at 6-month intervals, both groups underwent ultrasonographic examination for possible evidence of endometrioma recurrence and for evaluation of the absence, persistence, or recurrence of pain symptoms. Results: Two patients in the oral contraceptive group did not complete the study. After a mean follow-up of 22 months (range, 12-48 months), there were 2 (6.1%) endometrioma recurrences in the 33 patients who received postoperative oral contraceptives versus 1 (2.9%) recurrence in the 35 patients in the control group (not significant). The moderate-to-severe pain recurrence rate was 9.1% in the oral contraceptive group versus 17.1% in the control group (not significant). The mean time to recurrence of either symptoms or endometriomas was 18.2 months in the oral contraceptive group versus 12.7 months in the control group. The 12-month cumulative recurrence rate at life-table analysis was significantly lower for patients receiving oral contraceptives versus control subjects, whereas no significant difference was evident at 24 and 36 months. Conclusion: Postoperative administration of low-dose cyclic oral contraceptives does not significantly affect the long-term recurrence rate of endometriosis after surgical treatment. A delay in recurrence is evident at life-table analysis. (Am J Obstet Gynecol 2000;183:588-92.)

A Double‐Blind, Placebo‐Controlled Evaluation of the Effect of Oral Doses of Rizatriptan 10 mg on Oral Contraceptive Pharmacokinetics in Healthy Female Volunteers

Rizatriptan (MAXALT), a potent, oral 5-HT1B/1D agonist with a rapid onset of action, is available now for the acute treatment of migraine. This study examined the pharmacokinetic and clinical interaction between rizatriptan 10 mg and the components (ethinyl estradiol [EE] 35 micrograms and norethindrone [NET] 1.0 mg) of a well-established oral contraceptive combination product, ORTHO-NOVUM 1/35. Levels of sex hormone binding globulin (SHBG), a protein increased by EE to which NET binds, were also examined. In this two-period crossover study, 20 healthy young female subjects received a coadministration of 8 days of rizatriptan treatment (6 days of single-dose 10 mg rizatriptan and 2 days of multiple-dose rizatriptan, 10 mg q 4 hours for three doses, giving a total daily dose of 30 mg on Days 7 and 8) or matching placebo along with their daily dose (one tablet) of ORTHO-NOVUM 1/35 within their oral contraceptive cycle. Plasma was sampled for EE, NET, and SHBG concentrations. Safety evaluations included routine laboratory safety studies, physical examinations, and monitoring for ECG, vital signs, and adverse events. There were no statistically significant differences in any of the pharmacokinetic parameters of EE or NET between the rizatriptan and placebo treatment periods, thus indicating that rizatriptan had no meaningful effect on the disposition of either the EE or the NET component of ORTHO-NOVUM 1/35. The SHBG concentration did not change throughout the entire study. Clinically, coadministration of rizatriptan with ORTHO-NOVUM 1/35 was well tolerated. Blood pressure, heart rate, and temperature showed no consistent trend or clinically important changes. Adverse events following coadministration of rizatriptan with ORTHO-NOVUM 1/35 were similar to those reported when placebo was given with ORTHO-NOVUM 1/35. The findings of this study indicate that there is little potential for dosages as high as 30 mg/day, the maximum recommended dosing schedule, of rizatriptan to alter the plasma concentrations of oral contraceptives.

Reversible contraception: issues faced by emerging countries

There is no doubt that fertility regulation represents an important contribution to reproductive health. The role of fertility regulation in decreasing maternal mortality has been well documented. Thus, the use of contraceptives in developing countries has been projected to increase from 51% (1990) to 59% in the year 2000. Accordingly, 151 million surgical procedures for female and male sterilization, 8.7 billion cycles of oral contraceptives (OCs), 663 million doses of injectables, 310 million intrauterine devices (IUDs), and 44 billion condoms will be required in developing countries during the 1990s. Contraceptives are currently being manufactured in at least 27 developing countries. Subsidiaries of multinational companies are often involved in the local production of OCs and condoms, whereas most domestic IUD manufacturing ventures have been undertaken by local private companies. External assistance agencies have been active in supporting the local production of contraceptives.

Epithelial proliferation in the normal human breast in relation to endogenous hormones and oral contraceptive use

Abstract We studied proliferative activity in the breast tissue from 40 healthy premenopausal women who underwent reduction mammoplasty. Twenty-four women had regular menstrual cycles; 16 were taking combined oral contraceptives. Lobuloalveolar tissue was examined by means of the Ki-67/MIB 1 antibody to identify proliferating cells. The number of positive-staining cells was related to the estimated number of cells to form an activity ratio (AR). We found a significantly higher AR in the secretory compared with the proliferative phase of the menstrual cycle, and a tendency for higher AR values in late compared with early oral contraceptive treatment cycles. In multivariate analyses, the secretory phase was associated with a significantly higher AR, and oral contraceptive use was associated with a higher AR than natural cycles. Our data suggest that progesterone/progestins augment proliferation in the normal breast epithelium and highlight the complexity of cell regulatory factors affected by exogenous steroids.

Does the menstrual cycle and use of oral contraceptives influence the risk of low back pain? A prospective study among female soccer players.

Female sex hormones have been suggested to affect the risk of low back pain. One reason is the fact that back pain is a very common symptom during pregnancy. It also seems to be a more common problem among female than male athletes, e.g. in soccer. Although there are few scientific data supporting a relationship between female sex hormones, use of oral contraceptives and low back pain, many doctors and physiotherapists advise women with low back pain to avoid oral contraceptives. The aim of this study was to evaluate whether low back pain fluctuated during the menstrual cycle and differed between women using and not using oral contraceptives. A questionnaire was sent to 12 female soccer teams; 261 players answered and 50 players (28 with back pain and 22 controls) fulfilled the prospective study. At baseline the players underwent a thorough clinical examination and then filled in a diary concerning menstrual data, back pain, training and matches during one season. A total of 296 menstrual cycles was analysed. No difference in prevalence or severity of back pain was seen between the different phases of the menstrual cycle or between users and non-users of oral contraceptives. Our data do not support the hypothesis that low back pain is influenced by hormonal fluctuations during the menstrual cycle or by use of oral contraceptives.

Unusual Clinical Presentation of Endometrial Changes on the Low Dose Oral Contraceptive Pill

<h3>Background</h3> Endometrial changes have been previously described in a small series of adult patients treated with high dose combination oral contraceptive pills. <h3>Cases</h3> #1. EC is a 16yo G₀ who had menarche at age 13 and presented with a long history of irregular menses, menometrorrhagia, and anemia. At inital presenTation, her bleeding had increased to one pad/hr. and her hemalocrit was 15%. She was transfused and the bleeding stopped with LoOvral every 8hrs. She was discharged home on LoOvral every 12hrs. and iron. Two weeks after discharge, the LoOvral was decreased to one pill daily. Three weeks after discharge, she had some breakthrough bleeding and was told to take one pill twice a day. Two days later, she presented to the Emergency Department with severe spasmodic abdominal pain and vomiting. She was afebrile with stable vital. Of note, her WBC count was 12.1 with a normal differential. Her was 37%. and urine HCG was negative. Abdominal exam showed normal bowel sounds, significant guarding and diffuse abdominal pain to palpation. Bimanual pelvic exam revealed a uterus enlarged to twelve weeks size with an open cervical to that was filled with large amounts of pink-grey fleshy tissue. KUB, Ultrasound and CT scan were read as negative. With continued passage of tissue her symptoms resolved. She was admitted for observation and treatment of what was thought to be an incomplete spontaneoul abortion. However, she continued to deny sexual activity and her quantitative HCG returned negative. The pathology returned as decidualized endometrium with necrosis and chronic active inflammation, no chorionic villi were identified. The patient was discharged on cyclic LoOvral and iron and has had no problem over the last six months. #2. NC is a 12 yo G₀ who initally presented to the Gynecology Program with menometrorrhagia since menarche at age 11. At presentation, she had a hematocrit of 35% and negative urine HCG. She was prescribed LoOvral and stopped bleeding with the first pill from the pack. On the first placebo pill, she started bleeding and developed increasing abdominal pain particularly in the LLQ that became severe and spasmodic. On presentation to the Emergency Department, her vital signs were stable, her abdomen was soft and with good bowel sounds but became rigid with the onset of waves of pain. A single digit pelvic exam was difficult and limited. An ultrasound was normal. Her WBC was 11.5, HCT was 37%. and BHCG was negative. The pain resolved with spontaneous passage of a large amount of pink fleshy tissue per the vagina. Pathology reported the tissue to be a decidualized endometrial cast. The patient has been doing well for the last three months on cyclic oral contraceptives. <h3>Conclusion</h3> It has been described that the high dose oral contraceptive pill suppresses the endometrium. When given 20 days of Enovid, the 25th day endometrial biopsy showed that the stroma was decidua like. With further formulations of the combined pill in which the progestin were decreased to 5mg., the decidua like stromal reactions became weak and infrequent. In examining the continuous treatments with high dose oral contraceptives for endometriosis, samples from the endometrium exhibited diffuse, intense decidual reactions similar to that seen in the first and second trimesters of pregnancy. Both of our patients' presentations are unique variations of this pathology. Both were on doses of combination oral contraceptives significantly lower than those previously described to cause such intense decidual changes. In addition, something caused the marked decidual changes to be expelled by the uterus. We hypothesize that anovulatory cycles had created an endometrium that was exposed to high doses of unopposed estrogen creating an intense decidual reaction and with the addition of a small amount of progestin in LoOvral, the endometrium was sloughed.

Pituitary function is altered during the same cycle in women with polycystic ovary syndrome treated with continuous or cyclic oral contraceptives or a gonadotropin-releasing hormone agonist

To determine if continuous oral contraceptive (OC) therapy was superior to a cyclic regimen in achieving persistent pituitary suppression of LH in patients with polycystic ovary syndrome (PCOS). Fourteen women (ages 16 to 41 years) with PCOS received one of three treatment groups: continuous OC therapy (30 micrograms ethinyl E2 plus 150 micrograms desogestrel), cyclic OC therapy, or monthly injections of a GnRH agonist (GnRH-a, leuprolide acetate depot 3.75 mg) for 3 months. Basal hormone levels were obtained before initiating therapy, on days 15 to 17 of the 3rd month of treatment (study 1) and again on days 26 to 28 of the 3rd month (study 2). A GnRH stimulation test was also performed during study 1 and study 2. After 3 months of treatment, LH levels were decreased significantly in all groups with less effective suppression observed in the cyclic OC group compared with the continuous OC or GnRH-a groups. A significant rise in LH was found only in the cyclic OC group after 5 to 7 days of placebo treatment (study 1 versus study 2). An increase in T was also observed in the cyclic OC group during study 2, whereas the continuous OC and GnRH-a groups showed continued inhibition of T levels. Although there was no significant difference in LH area under the curve (AUC) measurements after GnRH stimulation in study 1 versus study 2, the LH AUC was significantly greater in both studies in the cyclic OC group compared with the continuous OC or GnRH-a groups. Increased LH secretion during the week of placebo in the cyclic OC group was associated with a concomitant increase in T. The striking rise in LH secretion after GnRH stimulation in the cyclic OC group may represent increased pituitary sensitivity in patients receiving cyclic OCs regardless of the phase of the treatment cycle, perhaps secondary to increased pituitary stores of LH in these women.