Efficacy of a new postpartum transition protocol for avoiding pregnancy.

INTRODUCTION: The postpartum period is a challenging time for family planning, especially for women who breastfeed. Breastfeeding delays the return of menses (lactational amenorrhea), but ovulation often occurs before first menses. For this reason, a protocol was developed to assist women in identifying their return of fertility postpartum to avoid pregnancy. METHODS: In this prospective, 12-month, longitudinal cohort study, 198 postpartum women aged 20 to 45 years (mean age, 30.2 years) were taught a protocol for avoiding pregnancy with either online or in-person instruction. A hand-held fertility monitor was used to identify the fertile period by testing for urinary changes in estrogen and luteinizing hormone, and the results were tracked on a web site. During lactational amenorrhea, urine testing was done in 20-day intervals. When menses returned, the monitor was reset at the onset of each new menstrual cycle. Participants were instructed to avoid intercourse during the identified fertile period. Kaplan-Meier survival analysis was used to calculate unintentional pregnancy rates through the first 12 months postpartum. RESULTS: There were 8 unintended pregnancies per 100 women at 12 months postpartum. With correct use, there were 2 unintended pregnancies per 100 women at 12 months. CONCLUSION: The online postpartum protocol may effectively assist a select group of women in avoiding pregnancy during the transition to regular menstrual cycles.

Estrogen and peptide YY are associated with bone mineral density in premenopausal exercising women.

BACKGROUND: In women with anorexia nervosa, elevated fasting peptide YY (PYY) is associated with decreased bone mineral density (BMD). Prior research from our lab has demonstrated that fasting total PYY concentrations are elevated in exercising women with amenorrhea compared to ovulatory exercising women. PURPOSE: The purpose of this study was to assess the association between fasting total PYY, average monthly estrogen exposure and BMD in non-obese premenopausal exercising women. METHODS: Daily urine samples were collected and assessed for metabolites of estrone 1-glucuronide (E1G) and pregnandiol glucuronide (PdG) for at least one menstrual cycle if ovulatory or a 28-day monitoring period if amenorrheic. Fasting serum samples were pooled over the measurement period and analyzed for total PYY and leptin. BMD and body composition were assessed by dual-energy X-ray absorptiometry. Multiple regression analyses were performed to determine whether measures of body composition, estrogen status, exercise minutes, leptin and PYY explained a significant amount of the variance in BMD at multiple sites. RESULTS: Premenopausal exercising women aged 23.8±0.9years with a mean BMI of 21.2±0.4kg/m(2) exercised 346±48min/week and had a peak oxygen uptake of 49.1±1.8mL/kg/min. Thirty-nine percent (17/44) of the women had amenorrhea. Fasting total PYY concentrations were negatively associated with total body BMD (p=0.033) and total hip BMD (p=0.043). Mean E1G concentrations were positively associated with total body BMD (p=0.033) and lumbar spine (L2-L4) BMD (p=0.047). The proportion of variance in lumbar spine (L2-L4) BMD explained by body weight and E1G cycle mean was 16.4% (R(2)=0.204, p=0.012). The proportion of variance in hip BMD explained by PYY cycle mean was 8.6% (R(2)=0.109, p=0.033). The proportion of variance in total body BMD explained by body weight and E1G cycle mean was 21.9% (R(2)=0.257, p=0.003). CONCLUSION: PYY, mean E1G and body weight are associated with BMD in premenopausal exercising women. Thus, elevated PYY and suppressed estrogen concentrations are associated with, and could be directly contributing to, low BMD in exercising women with amenorrhea, despite regular physical activity.

Long-term estrogen deficiency lowers regional blood flow, resting systolic blood pressure, and heart rate in exercising premenopausal women.

The cardiovascular consequences of hypoestrogenism in premenopausal women are unclear. Accordingly, the influence of menstrual status and endogenous estrogen (E(2)) exposure on blood pressure (BP), heart rate (HR), and calf blood flow in young (18-35 yr) regularly exercising premenopausal women with exercise-associated menstrual aberrations was investigated. Across consecutive menstrual cycles, daily urinary ovarian steroid levels were analyzed, and the area under the curve was calculated to determine menstrual status and E(2) exposure. BP, HR, blood flow, vascular conductance, and resistance were measured at baseline and following ischemic calf exercise. Exercising subjects consisted of 14 ovulatory (ExOv), 10 short-term (anovulatory and 100 days amenorrhea; LT-E(2) Def) E(2)-deficient women. Nine sedentary ovulatory subjects (SedOv) were also studied. All groups were similar in age (24.8 +/- 0.7 yr), height (164.8 +/- 1.3 cm), weight (57.9 +/- 0.9 kg), and body mass index (21.3 +/- 0.3 kg/m(2)). E(2)-deficient groups had lower (P < 0.002) E(2) exposure compared with ovulatory groups. Resting systolic BP, HR, blood flow, and vascular conductance were lower (P < 0.05) and vascular resistance higher (P < 0.05) in LT-E(2) Def compared with both ovulatory groups. Peak ischemic blood flow, vascular conductance, and HR were also lower (P < 0.05) and vascular resistance higher (P < 0.05) in LT-E(2) Def compared with all other groups. Our findings show that exercising women with long-term E(2) deficiency have impaired regional blood flow and lower systolic BP and HR compared with exercising and sedentary ovulatory women. These cardiovascular alterations represent markers of altered vascular function and autonomic regulation of which the long-term effects remain unknown.

Persistent low-level "real" human chorionic gonadotropin: a clinical challenge and a therapeutic dilemma.

OBJECTIVE: The finding of persistent low-level human chorionic gonadotropin (hCG) with or without a preceding pregnancy event presents a rare but clinically important challenge and a therapeutic dilemma. These are patients with "real" hCG shown by the positive test in both serum and urine or by specialized testing. The problems associated with "phantom" hCG have been recognized and should now be clinically resolvable. Four cases of low-level "real" hCG are described to illustrate the problems encountered, the management, and the resolution achieved. METHODS: Two patients presented with persistent low-level hCG after hydatidiform mole pregnancy, one after an early pregnancy loss and one as amenorrhea and irregular bleeding. A detailed clinical description is provided to illustrate the difficulties encountered. RESULTS: All patients have real hCG. The hCG level of Patient 1 was responsive to hormonal contraception and disappeared with such medication. Over a period of 3 years hCG reappeared whenever estrogen was stopped. Patient 2 achieved two pregnancies and the hCG subsequently disappeared. The hCG in Patient 3 persisted over a period of 6 years although she is now menopausal. Patient 4 developed metastatic placental site trophoblastic tumor after 2 1/2 years of observation of low-level hCG. CONCLUSIONS: The finding of unexplainable low-level hCG in a patient without evidence of a uterine lesion or of trophoblastic metastases provides a therapeutic challenge. The administration of single-agent chemotherapy had no effect on the level of hCG in the three patients to whom it was administered. The administration of multiple-agent chemotherapy appears unjustified in the absence of a demonstrable trophoblastic tumor. A small number of trophoblastic cells must be providing this hCG and these cells may be quiescent for years. Nevertheless these cells may proliferate and manifest themselves as trophoblastic tumor. Continuing long-term surveillance of these patients is necessary.

Effect of hyperandrogenism and menstrual cycle abnormalities on bone mass and bone turnover in young women.

OBJECTIVE: Prolonged period of amenorrhoea are regarded as a risk factor for the appearance of osteoporosis. Amenorrhoea is a feature of different pathological conditions with heterogeneous endocrine profiles. We evaluated bone mineral metabolism in patients with polycystic ovary syndrome (PCOS), hypothalamic amenorrhoea and idiopathic hirsutism in order to establish the relative importance for the maintenance of normal bone mass of ovulatory cycles and androgen and oestrogen production. PATIENTS AND MEASUREMENTS: Bone mineral density (BMD), bone turnover markers and endocrine profile were evaluated in 51 patients with PCOS, 24 patients with idiopathic hirsutism, 26 patients with hypothalamic amenorrhoea and 35 healthy women. Body mass index (BMI) ranged between 20.1 and 31.0 kg/m2, and age from 17 to 33 years. Thirty-eight of the PCOS patients were amenorrhoeic (< 4 menstrual cycles/year). RESULTS: Spine and femoral BMD were significantly decreased and bone markers (serum osteocalcin, and urinary excretion of free deoxypyridinoline, cross-linked N-telopeptide and hydroxyproline) significantly increased in the patients with hypothalamic amenorrhoea, when compared to control subjects and the other two patient groups. In the sub-group of PCOS patients with amenorrhoea, spine and femoral neck BMD was significantly lower than in patients with idiopathic hirsutism and the non-amenorrhoeic PCOS patients. In all PCOS patients, spine and neck BMD were positively correlated (P < 0.05) with serum androstenedione and free testosterone levels. CONCLUSIONS: The results of this study suggest that in patients with polycystic ovary syndrome the deleterious effect on bone of amenorrhoea is balanced by androgen overproduction.

Steroid secretory characteristics of a virilizing adrenal adenoma in a woman.

A tumour of the left adrenal gland was identified in a woman who presented with virilization and secondary amenorrhea. Preoperatively, the plasma levels of dehydroepiandrosterone sulphate, dehydroepiandrosterone, androstenedione, testosterone, 5 alpha-dihydrotestosterone and 5-androstene-3 beta,17 beta-diol were elevated two- to fourfold whereas those of urinary 17-ketosteroids were elevated more than tenfold. The production rate of dehydroepiandrosterone sulphate was more than 16 times that in normal women whereas those of dehydroepiandrosterone, testosterone and androstenedione were approximately twofold greater; plasma testosterone was derived almost entirely from the peripheral conversion of androstenedione. Blood was obtained by catheterization of the ovarian veins, left adrenal gland vein and inferior vena cava (at two different sites) and plasma steroid levels were determined: testosterone and cortisol levels were elevated in all blood samples whereas those of androstenedione, dehydroepiandrosterone sulphate and 11-desoxycortisol were approximately six- to eightfold, 1.5-fold and nine- to 22-fold higher in the effluent on the left adrenal gland/tumour compared with the levels in the other compartments. Blood was collected hourly for 24 h to determine steroid levels under basal conditions and, also, after ACTH treatment. Plasma cortisol levels increased markedly upon ACTH administration and fell to very low levels 11 h later, but those of androstenedione, testosterone, dehydroepiandrosterone, 5-androstene-3 beta,17 beta-diol and dehydroepiandrosterone sulphate were not affected by ACTH treatment. A histological diagnosis of cortical adenoma of the extirpated tumour was made. Tissue explants and adenoma cells were maintained in culture to characterize the steroid-metabolizing properties of the tumour. The secretion of dehydroepiandrosterone sulphate by tissue explants was highly initially, but declined to almost undetectable levels after 5 days in culture. In the presence of ACTH, dehydroepiandrosterone sulphate secretion remained elevated throughout the entire study up to 5 days. Basal secretion of dehydroepiandrosterone sulphate, androstenedione, 11-desoxycortisol, cortisol, testosterone and 11 beta-hydroxyandrostenedione by adenoma cells was either very low or undetectable. In the presence of ACTH, dibutyryl cyclic AMP or cholera toxin the secretion of dehydroepiandrosterone sulphate, androstenedione and 11-desoxycortisol increased markedly with time in culture up to 3 days, whereas the other steroids were undetected in the medium. A homogenate of adenoma tissue metabolized testosterone to androstenedione, but the conversion of androstenedione to testosterone was minimal. The findings of this study served to establish that virilization in this woman was due at least in part, to excess testosterone--and testosterone-derived 5 alpha-dihydrotestosterone--produced at extra-adrenal tissue sites almost exclusively through metabolism of tumour-secreted androstenedione.(ABSTRACT TRUNCATED AT 400 WORDS)

Interrelation between Western type cancers and non-Western type cancers as regards their risk variation in time and space. IV. Hormonal transition of Japanese women from the pro-cervical cancer age through the pro-endometrial cancer age to the pro-hypogonadism age.

Chronological trend of urinary steroid excretions in Japanese women was investigated during the period of June 1972 to August 1986 using healthy women of urban and rural origins, patients with breast cancer and patients with either cervical cancer or endometrial cancer. The excretions of 14 neutral steroids were estimated by gas liquid chromatography, and the obtained data were tentatively correlated with the epidemiological backgrounds. In the course of the chronological transition from the 1st stage (1972-1974) to the 2nd stage (1975-79), the urinary steroid pattern of Japanese women with and without cancer experienced a common change to produce specific deviations that were in agreement with the hormonal characteristics of a pill user or of an endometrial cancer patient. At the 3rd stage (1980-86), patients with either cervical cancer or endometrial cancer were distinguished from 1st stage controls by non-specific depression of all androgens, progestins and corticosteroids in urine. Throughout the whole period, both the risk for cervical cancer and the reproductive activity (birth rate) were found to decrease continuously in Japanese women. Evidence was presented to suggest that the above deterioration of the hormonal environment in Japanese women could be related to the stress of modern life rather than to defects in the diet. On the basis of the above findings, the 1st, 2nd and 3rd stages of our investigation were tentatively termed the pro-cervical cancer age, the pro-endometrial cancer age and the pro-hypogonadism age. The relation between the chronological change of urinary steroids and that of the epidemiological background was analyzed from the view point of population ecology.

Fasting urinary calcium/creatinine and hydroxyproline/creatinine values in young women with amenorrhoea and in matched eumenorrhoeic controls.

The present study was undertaken to compare fasting urinary calcium/creatinine (Ca/Cr) and hydroxyproline/creatinine (HP/Cr) values in young amenorrhoeic women with those of age and weight-matched menstruating women and to see whether restoration of menstruation would influence values. Thirty amenorrhoeic patients were matched with 30 controls. Higher Ca/Cr (0.393 (SD 0.213) vs 0.142 (0.89), p less than 0.001) and HP/Cr (0.025 (0.005) vs 0.020 (0.007), p less than 0.005) values were found in patients with hyperprolactinaemia or hypothalamic dysfunction associated with weight loss, anorexia nervosa or excessive exercise (n = 20), suggesting excessive bone loss in these amenorrhoeic patients, who are frequently oestrogen deficient. Furthermore when 9 amenorrhoeic patients with hypothalamic dysfunction became eumenorrhoeic their urinary Ca/Cr values fell (p less than 0.02). However, amenorrhoeic patients with polycystic ovaries (n = 10) had similar Ca/Cr and HP/Cr values as their controls. It is therefore probable that amenorrhoeic patients with polycystic ovaries are not at risk of osteopenia. The present findings suggest measurements of fasting urinary Ca/Cr and HP/Cr values are likely to prove useful in identifying patients with amenorrhoea who are rapidly losing bone, and in assessing their responses to therapy.

Induction of ovarian activity by pulsatile infusion of LHRH in women with lactational amenorrhoea.

Four fully breast-feeding women at 6 weeks post partum were injected with LHRH (0.1 microgram/kg) every 94 min by pulsatile infusion pump. While follicular development occurred in all women, and evidence of luteinization was apparent in three out of four, normal ovulation and luteal function did not occur. This suggests that a simple disturbance in the pulsatile pattern of LHRH secretion may not, in itself, be enough to explain the suppression of ovarian activity during lactation.

[Applications of the urocytogram in primary-secondary amenorrhea in adolescents]. / Applications de l'urocytogramme dans les aménorrhées primo-secondaires chez les adolescentes.

In the urinary sediment, the cellular material mainly originates from cells of the bladdertrigone. These cells are submitted to hormonal stimulation and their study constitutes the base of a cytological method called "urocytogram". The urinary sediment was examined in thirty-five young girls with backward puberty. The repeated examinations contribute to differential diagnosis and help in etiologic diagnosis. Whenever it is necessary to investigate adolescent's sex hormones, an urocytogram, a simple and painless method, is indicated.

Oestrogen-gonadotrophin feedback abnormalities in hyperprolactinaemic amenorrhoea demonstrated by the response to clomiphene administration.

Clomiphene was administered to 16 patients with elevated serum prolactin levels in doses of 100, 200 and 300 mg/day for five days in succeeding months and total urinary oestrogens estimated on days 0, 5, 8, 12 and 15 following commencement of treatment. The responses were compared with six patients who were amenorrhoeic but had normal serum prolactin levels and absent positive feedback to oestrogen. The increased outputs of oestrogens were similar in the two groups. In the hyperprolactinaemic group 5 out of 16 subjects showed evidence of ovulation whilst the remainder showed a secondary failure of response. Six subjects who failed to ovulate were treated with clomiphene and human chorionic gonadotrophin (HCG) and ovulations were induced in 31 out of 34 treatment cycles but no pregnancies were achieved. The responses to clomiphene therapy in the hyperprolactinaemic subjects were compared to the assessment of positive feedback mechanisms by means of oestrogen provocation and oestrogen amplification tests and good correlation was obtained. Only those with evidence of positive feedback to these tests were likely to ovulate on clomiphene.

[Uncommonly high concentration of estrone of adrenal origin in a case of androgenic obesity, anovulation and amenorrhea]. / Niezwykle wysokie wartosci estronu pochodzenia nadnerczowego w przypadku androgennej otylosci,braku owulacji i miesiaczki.

PIP: The case of a 35-year-old woman who demonstrated androgenic obesity, absence of ovulation, and amenorrhea is examined. This patient showed arterial hypertension, diabetes mellitus, hirsutism, and anovulatory cycles. A very high concentration of estrone was noted in the urine, originating in the adrenal glands. These indications are generally considered during evaluation of breast or uterine cancer threat. Administration of dexamethasone led to a decrease in urinary estrone to insignificant levels. Stimulation with human chorionic gonadotropin caused an increase in ovarian activity. The disruptions this patient suffered were attributed to hormonal imbalances attributed to her obesity, primarily in regard to estrogen metabolism.^ieng

Use of clomiphene and luteinizing hormone/follicle stimulating hormone-releasing hormone in investigation of ovulatory failure.

A luteinizing hormone/follicle-stimulating hormone-releasing hormone (LH/FSH-RH) test was performed in 70 women with amenorrhoea or anovulatory infertility, or both, and a clomiphene stimulation test was also performed in 24 of these patients. Most patients responded to LH/FSH-RH with significant increases in LH and FSH. In women with gonadal dysgenesis or premature ovarian failure exaggerated responses were observed after LH/FSH-RH and there was no change in high basal LH levels after clomiphene. Patients with absent or impaired responses to LH/FSH-RH failed to respond to clomiphene. All patients with anovulatory menstrual cycles responded to both LH/FSH-RH and clomiphene, while seven out of 13 amenorrhoeic patients with a normal LH/FSH-RH response showed an early LH rise during clomiphene treatment and six were unresponsive. These results suggest a difference between the two groups at hypothalamic level with consequent therapeutic implications.