Angelica Lindén Hirschberg

Testosterone for Low Libido in Postmenopausal Women Not Taking Estrogen

BACKGROUND The efficacy and safety of testosterone treatment for hypoactive sexual desire disorder in postmenopausal women not receiving estrogen therapy are unknown. METHODS We conducted a double-blind, placebo-controlled, 52-week trial in which 814 women with hypoactive sexual desire disorder were randomly assigned to receive a patch delivering 150 or 300 microg of testosterone per day or placebo. Efficacy was measured to week 24; safety was evaluated over a period of 52 weeks, with a subgroup of participants followed for an additional year. The primary end point was the change from baseline to week 24 in the 4-week frequency of satisfying sexual episodes. RESULTS At 24 weeks, the increase in the 4-week frequency of satisfying sexual episodes was significantly greater in the group receiving 300 microg of testosterone per day than in the placebo group (an increase of 2.1 episodes vs. 0.7, P<0.001) but not in the group receiving 150 microg per day (1.2 episodes, P=0.11). As compared with placebo, both doses of testosterone were associated with significant increases in desire (300 microg per day, P<0.001; 150 microg per day, P=0.04) and decreases in distress (300 microg per day, P<0.001; 150 microg per day, P=0.04). The rate of androgenic adverse events - primarily unwanted hair growth - was higher in the group receiving 300 microg of testosterone per day than in the placebo group (30.0% vs. 23.1%). Breast cancer was diagnosed in four women who received testosterone (as compared with none who received placebo); one of the four received the diagnosis in the first 4 months of the study period, and one, in retrospect, had symptoms before undergoing randomization. CONCLUSIONS In postmenopausal women not receiving estrogen therapy, treatment with a patch delivering 300 microg of testosterone per day resulted in a modest but meaningful improvement in sexual function. The long-term effects of testosterone, including effects on the breast, remain uncertain. (ClinicalTrials.gov number, NCT00131495.)

Pregnancy and neonatal outcomes in women with eating disorders.

OBJECTIVE: This study was initiated to examine pregnancy and neonatal outcomes in women with past or current eating disorders as compared with a control group. METHODS: Forty-nine nulliparous nonsmoking women previously diagnosed with eating disorders (24 anorexia nervosa, 20 bulimia nervosa, 5 eating disorders not otherwise specified) and 68 controls were recruited in early pregnancy. Data on antenatal complications, mode of delivery, and neonatal outcome variables were collected. For comparisons between groups 1-way analysis of variance or &khgr;2 test was used. RESULTS: Twenty-two percent of the patients had a verified relapse in eating disorders during pregnancy. Women with past or current eating disorders were at increased risk of hyperemesis (P < .01) and delivered infants with significantly lower birth weight (P < .01) and smaller head circumference (P < .001) as compared with controls. They were also at greater risk of delivering infants with microcephaly (P < .05) and small for gestational age infants (P < .05). CONCLUSION: Pregnant women with past or active eating disorders seem to be at greater risk for delivering infants with lower birth weight, smaller head circumference, microcephaly, and small for gestational age. LEVEL OF EVIDENCE: II-2

A randomized trial of the effect of estrogen and testosterone on economic behavior

Existing correlative evidence suggests that sex hormones may affect economic behavior such as risk taking and reciprocal fairness. To test this hypothesis we conducted a double-blind randomized study. Two-hundred healthy postmenopausal women aged 50–65 years were randomly allocated to 4 weeks of treatment with estrogen, testosterone, or placebo. At the end of the treatment period, the subjects participated in a series of economic experiments that measure altruism, reciprocal fairness, trust, trustworthiness, and risk attitudes. There was no significant effect of estrogen or testosterone on any of the studied behaviors.

Testosterone inhibits estrogen/progestogen-induced breast cell proliferation in postmenopausal women.

Objective: During the past few years serious concern has been raised about the safety of combined estrogen/progestogen hormone therapy, in particular about its effects on the breast. Several observations suggest that androgens may counteract the proliferative effects of estrogen and progestogen in the mammary gland. Thus, we aimed to study the effects of testosterone addition on breast cell proliferation during postmenopausal estrogen/progestogen therapy. Design: We conducted a 6-month prospective, randomized, double-blind, placebo-controlled study. A total of 99 postmenopausal women were given continuous combined estradiol 2 mg/norethisterone acetate 1 mg and were equally randomly assigned to receive additional treatment with either a testosterone patch releasing 300 &mgr;g/24 hours or a placebo patch. Breast cells were collected by fine needle aspiration biopsy at baseline and after 6 months, and the main outcome measure was the percentage of proliferating breast cells positively stained by the Ki-67/MIB-1 antibody. Results: A total of 88 women, 47 receiving active treatment and 41 in the placebo group, completed the study. In the placebo group there was a more than fivefold increase (P < 0.001) in total breast cell proliferation from baseline (median 1.1%) to 6 months (median 6.2%). During testosterone addition, no significant increase was recorded (1.6% vs 2.0%). The different effects of the two treatments were apparent in both epithelial and stromal cells. Conclusions: Addition of testosterone may counteract breast cell proliferation as induced by estrogen/progestogen therapy in postmenopausal women.

Hyperandrogenicity is an alternative mechanism underlying oligomenorrhea or amenorrhea in female athletes and may improve physical performance

OBJECTIVE To evaluate endocrine mechanisms underlying oligomenorrhea or amenorrhea in female athletes. DESIGN Cross-sectional study. SETTING Womens health clinical research unit at a university hospital. PATIENT(S) Age- and BMI-matched groups of athletes active in endurance sports with and without menstrual disturbances and regularly cycling sedentary controls. INTERVENTION(S) Groups were compared with respect to endocrine status, body composition, and physical performance. MAIN OUTCOME MEASURE(S) Identification of a subgroup of oligomenorrheic or amenorrheic athletes with increased androgen levels and anabolic body composition. RESULT(S) A subgroup of 8 of 25 athletes with menstrual disturbances had significantly higher serum levels of free and total testosterone, androstenedione, LH-FSH ratio, and lower SHBG levels than did all other groups. Other oligomenorrheic or amenorrheic athletes had normal values comparable to those in regularly menstruating athletes and controls. The hyperandrogenic subgroup showed a more anabolic body composition, with higher total bone mineral density and upper-lower fat mass ratio than did oligomenorrheic or amenorrheic athletes with normal androgen levels. The hyperandrogenic subgroup had the highest VO2 max and the highest performance values in general. CONCLUSION(S) Menstrual disturbances in female athletes are often explained as a consequence of hypothalamic inhibition and caloric deficiency. We suggest that essential hyperandrogenism is an alternative mechanism underlying oligomenorrhea or amenorrhea in some female athletes and may imply an advantage for physical performance.

Sex hormones, appetite and eating behaviour in women

Sex hormones play essential roles in the regulation of appetite, eating behaviour and energy metabolism and have been implicated in several major clinical disorders in women. Estrogen inhibits food intake, whereas progesterone and testosterone may stimulate appetite. This review describes recent findings concerning interactions between sex hormones and neuroendocrinological mechanisms in the control of appetite and eating in women. Furthermore, we are gaining insights into the roles played by sex hormones in the development of eating disorders and obesity. For instance, androgens may promote bulimia by stimulating appetite and reducing impulse control, a proposal supported by the observation that antiandrogenic treatment attenuates bulimic behaviour. Androgens are also involved in the pathophysiology of abdominal obesity in women. On the other hand, hormone replacement therapy with estrogen counteracts the weight gain and accumulation of abdominal fat associated with the menopausal transition. In conclusion, sex hormones and/or agents that exhibit similar activities may provide novel strategies for the treatment of eating disorders and android obesity, two of the most serious health problems for women today.

Randomized comparison of the influence of dietary management and/or physical exercise on ovarian function and metabolic parameters in overweight women with polycystic ovary syndrome

OBJECTIVE To compare the influence of dietary management and/or physical exercise on ovarian function and metabolic variables in women with polycystic ovary syndrome (PCOS). DESIGN Randomized 4-month trial with three interventions and a long-term follow-up. SETTING Womens health clinical research unit at a university hospital. PATIENT(S) Fifty-seven overweight/obese women with PCOS. INTERVENTION(S) Dietary management, physical exercise, or both, using programs individually adapted and supervised by a dietician and/or a physical therapist. MAIN OUTCOME MEASURE(S) Ovarian function, endocrinologic, and metabolic status and body composition. RESULT(S) On average, body mass index was reduced 6% by the dietary management, 3% by the exercise, and 5% by the combined interventions. Lower body fat and lean body mass were significantly decreased in the dietary groups, whereas upper body fat was lowered and lean body mass maintained by exercise alone. The menstrual pattern was significantly improved in 69% and ovulation confirmed in 34% of the patients, with no differences among the groups. The strongest predictor of resumed ovulation was a high serum level of insulin-like growth factor-binding protein 1 after the intervention. Follow-up of one-half of the patients for a median of 2.8 years revealed sustained weight reduction and improvement in menstrual pattern. CONCLUSION(S) Dietary management and exercise, alone or in combination, are equally effective in improving reproductive function in overweight/obese women with PCOS. The underlying mechanisms appear to involve enhanced insulin sensitivity. Supportive individualized programs for lifestyle change could exert long-term beneficial effects.

Muscle strength and endurance do not significantly vary across 3 phases of the menstrual cycle in moderately active premenopausal women.

ObjectiveTo investigate muscle strength and muscle endurance in women during 3 well-determined phases of the menstrual cycle: early follicular phase, ovulation phase, and midluteal phase. DesignProspective, within-woman analysis was performed of muscle strength and muscle endurance by repeated measures analysis of variance in 3 hormonally verified phases of 2 consecutive menstrual cycles. ParticipantsFifteen female subjects with moderate physical activity level and regular menstrual cycles volunteered to participate in the study. Analyses are based on 10 subjects who completed 2 consecutive menstrual cycles with hormonally verified phases. Main Outcome MeasurementsHandgrip strength, 1-leg hop test, isokinetic muscle strength, and muscle endurance were measured in 2 consecutive menstrual cycles in the early follicular phase, in the ovulation phase, and in the midluteal phase. Isokinetic muscle strength and endurance were tested with knee extension exercise on a standard instrument. Menstrual cycle phases were determined by analysis of sex hormone levels in serum, and ovulation was detected by luteinizing hormone surge in urine. ResultsNo significant variation in muscle strength or muscle endurance could be detected during different well-determined phases of the menstrual cycle. ConclusionsThis study detected no significant variation in muscle strength and muscle endurance during the menstrual cycle. In contrast to other studies showing variations in strength and endurance during the menstrual cycle, the present study was hormonally validated and was repeated in 2 consecutive menstrual cycles. However, it is unknown whether these data in moderately active university students would be relevant to the highly trained woman athlete.

The Influence of Menstrual Phases on Pain Modulation in Healthy Women

UNLABELLED This study investigated if conditioned pain modulation (CPM) varies across the menstrual cycle in healthy, normally menstruating women and investigated correlations between sex hormone levels and CPM across the menstrual cycle. Thirty-six normally menstruating women were tested during 3 phases of the menstrual cycle: early follicular, ovulatory, and midluteal, confirmed by hormone determinations. Mechanical pressure (test stimulus) was applied to the masseter muscle and the induced pain assessed before, during, and after immersion of the hand into ice water (conditioning stimulus) to activate CPM or tepid water (control). Conditioning pain, ie, pain in the hand during CPM/control experiment, and tolerance time were also measured. Test pain intensity was suppressed during CPM in all phases (P < .001), but with more effective suppression during the ovulatry than during the early follicular phase (P < .05). There were no changes in test pain intensity during the control experiment and no significant differences in conditioning pain, or tolerance time between phases. In conclusion, our results showed more effective pain modulation in the ovulatory phase of the menstrual cycle, when estradiol levels are high and progesterone levels are low, than in the early follicular phase when both these hormones are low. PERSPECTIVE Deficient pain modulation is believed to be an important pathogenic factor in many chronic pain conditions that affect women. This article shows that sex hormones modulate conditioned pain modulation, because pain inhibition was more effective in the ovulatory phase of the menstrual cycle than in the early follicular phase.

Hyperandrogenism may explain reproductive dysfunction in olympic athletes.

PURPOSE Female athletes are known to be at risk for reproductive dysfunction and osteopenia because of energy deficiency. Although endocrine balance and an optimal body composition are essential for top elite performance, these parameters have not yet been explored fully in Olympic sportswomen. The objective of this study, therefore, was to characterize the menstrual status, body composition, and endocrine balance in female Olympic athletes participating in different disciplines. METHODS Ninety Swedish female Olympic athletes underwent a gynecologic examination that included vaginal examination by ultrasound and determination of body composition. In addition, blood samples were collected for the analysis of reproductive hormones and biomarkers of energy availability. RESULTS Of all the athletes, 47% were using hormonal contraception (HC). Menstrual dysfunction (MD) was common (27%) among those not using HC and, particularly, in endurance athletes. However, the proportion of body fat and biomarkers of energy availability were within the normal ranges and none exhibited osteopenia. On the contrary, bone mineral density was generally high, particularly in the power athletes. The most common diagnosis associated with MD was polycystic ovary syndrome (PCOS) and not hypothalamic inhibition because of energy deficiency. CONCLUSIONS Female Olympic athletes participating in different sports were found to have an anabolic body composition and biomarkers of energy availability within the normal ranges. Most cases of menstrual disturbances observed were due to PCOS. These findings challenge the contemporary concept that reproductive dysfunction in sportswomen is typically a consequence of chronic energy deficiency.