The use of oral contraceptives as a prevention of recurrent premenstrual psychosis.

Premenstrual psychosis is a rare and not formally recognized disorder (DSM-IVR, ICD-10). The literature mainly consists of clinical cases. There have been preliminary reports of improvement in such cases after administration of oral contraceptives. We present a case of premenstrual psychosis in which hormonal treatment was effective in preventing symptomatic relapses.

Complexion changes in oral contraceptive users. Results from a phase IV multicenter trial evaluating the safety and efficacy of ethynodiol diacetate, 1 mg, with ethinyl estradiol, 35 micrograms.

An open-label, phase IV, multicenter survey of obstetrician-gynecologists was conducted to evaluate the efficacy and safety of a low-dose monophasic oral contraceptive, ethynodiol diacetate, 1 mg, with ethinyl estradiol, 35 micrograms. Surveys from 983 community-based physicians reported on 6,382 women. Most patients did not experience "clinically noticeable complexion changes" (5,695/6,382, or 89.2%). Of the 687 patients with complexion changes, nearly three-fourths reported an improvement (501/687, or 72.9%). A follow-up questionnaire was sent to 127 respondents (18.6%) who reported worsening of the complexion; 70% of the questionnaires were returned. Most complexion worsening was of slight degree (63%), reported by the patient and not the physician (84% vs. 16%), and experienced during the first two to three months (84%). Although the literature includes many references to skin condition "improvement" on oral contraceptives, this report of a descriptive study gives clinicians as estimate of the incidence and severity of complexion changes in actual use.

PIP: An open-label, phase IV, multicenter survey of obstetrician-gynecologists was conducted to investigate the efficacy and safety of a low-dose monophasic oral contraceptive (OC), ethynodiol diacetate, 1 mg, with ethinyl estradiol (EE), 35 mcg. Surveys from 983 community-based physicians reported on 6382 women, most of whom did not experience "clinically noticeable complexion changes" (5695/6382 or 89.2%). Of the 687 who did, nearly 3/4 reported an improvement (501/587 or 72.9%). A followup questionnaire was sent to 127 respondents (18.6%) who reported worsening of their complexions; 70% of the questionnaires were returned. Most had a slight degree of complexion worsening (63%) as reported by the patient and not the physician (84% vs 16%), and these changes were experienced during the 1st 2-3 months (84%). Although the literature includes many references to skin condition improvement while taking OCs, this report of a descriptive study gives clinicians an estimate of the incidence and severity of complexion changes during actual use. (author's modified).

Oral contraception: a review.

PIP: This review of the development of oral contraceptives (OCs) begins with a summary of research between 1920 and 1950 that led to the first highly effective, orally active progestogen for human use. Enovid by Searle, the first marketed OC, began being distributed in 1960; it was combination of 9.85 mg of norethynodrel and .150 mg of mestranol. Research on combination norethynodrel-containing products revealed that the dosage was too high. Discussion focuses on preparations containing norethisterone, norethisterone acetate, medroxyprogesterone diacetate, norgestrel, other Norgestrel products available outside the US, progestogen, as well as the sequentials and the multiphasics. The active phase of clinical development was during 1950s and 1960s. The Food and Drug Administration (FDA) had an active role in regulating OCs; OCs with more than .05 mg of estrogen were removed from the market; FDA permitted ethinyl estradiol as a substitute for mestranol. Pregnancy rates appear lower in clinical trials than among the general population. 3% during the first year is considered more characteristics of the failure rate among the general population. It appears that intermenstrual bleeding (IMB) has decreased as doses have been decreased, but strict comparison between studies and over time is not possible. There is valid documentation of the rate of IMB with low-dose OCs, or of differences between new OC users and prior OC users, or of the impact of the strength of OC components.^ieng

Oral contraceptives and coronary artery atherosclerosis of cynomolgus monkeys.

Studies of both human and nonhuman primates show an inverse relationship between high-density lipoprotein (HDL) cholesterol concentrations and coronary artery atherosclerosis. For this reason, there has been concern that the HDL cholesterol-lowering effect of oral contraceptives might exacerbate coronary artery atherosclerosis. We studied three groups of adult female cynomolgus macaques fed a moderately atherogenic diet: a control group, a group given ethinyl estradiol and norgestrel, and another group given ethinyl estradiol and ethynodiol diacetate. Norgestrel and ethynodiol diacetate, co-administered with ethinyl estradiol, lowered the plasma concentrations of HDL cholesterol. However, the extent of coronary artery atherosclerosis was lessened by both contraceptives, especially among females at high risk based on their plasma lipid profiles.

[Results of treatment of atypical endometrial hyperplasia]. / Rezultaty lecheniia atipicheskoi giperplazii éndometriia.

PIP: To evaluate the risk of transformation of atypical endometrial hyperplasia (AEH) into endometrial cancer, a group of 190 women who underwent treatment for AEH was followed up. The group included 53 women of child-bearing age, 81 in the premenopausal period, and 56 in the postmenopausal period. The most frequent clinical manifestation of AEH was metrorrhagia. The patients with mild or moderate AEH received conservative treatment, while the patients with severe AEH complicated by other gynecological diseases (uterine myoma or adenomyosis) received surgical treatment. Conservative hormonal treatment included cyclic administration of infecundin, bisecurin, hydroxyprogesterone caproate. The average duration of hormone therapy was 12 months. The 1st follow-up examination was conducted 3 months after the onset of the treatment. Of 53 patients of child-bearing age, 18 had recurrence of AEH (1 within 6 months after the initiation of the treatment, 5 within 6 months, 10 within 1-3 years, 1 within 5 years, and 1 within 9 years). Endometrial cancer was diagnosed in 2 patients (7 and 10 years after treatment of AEH). Of 81 patients in the premenopausal period, 29 developed recurrence of AEH within 3 months to 3 years of the treatment; endometrial cancer was detected in 2. Of 56 patients in the postmenopausal period, 16 developed recurrence within 3-6 months of the treatment; endometrial cancer was diagnosed in 3 patients. These findings indicate that majority of the patients with AEH can be cured by hormonal therapy, but the high risk of cancer development (3.7%) requires longterm follow-up.^ieng

Serum thymidine activity and somatomedin-C levels in children and adolescents with Turner's syndrome: effect of chronic estrogen and progestogen replacement therapy.

Turner's syndrome has been used as a model of primary hypogonadism to assess the role of estrogen-progestogen replacement therapy on serum thymidine activity (TA) and somatomedin-C (Sm-C) levels. 33 subjects with gonadal dysgenesis were studied: 10 untreated and 13 treated with estrogen-progestogen combination. In 10 untreated patients serum TA was 1.02 +/- (SEM) 0.04 U/ml and serum Sm-C value was 27.82 +/- 4.14 nmol/l, both similar to those in the age-matched normal children. A positive correlation was found between Sm-C and the bone age (r = 0.891, p less than 0.002). In the 13 treated subjects, the estrogen-progestogen combination as replacement therapy induced a significant increase in Sm-C level (40.52 +/- 4.30 nmol/l, p less than 0.05). No variation was observed for serum thymidine activity between the two groups of subjects.

Spironolactone in combination with an oral contraceptive: an alternative treatment for hirsutism.

The clinical efficacy of a combination of spironolactone and an oral contraceptive pill (Conova 30) was assessed in 23 patients presenting with hirsutism of whom 20 completed 6 months of treatment. Of the 20 patients, 16 showed improvement on objective (Ferriman & Gallwey hair score) and subjective assessment. Serum levels of androgens (testosterone, androstenedione and 17-hydroxy progesterone) were suppressed and sex hormone binding globulins were elevated. Nausea was the only significant side effect.

The effect of progestins on the mitotic activity of uterine fibromyomas.

Previous studies have shown increased mitotic activity in uterine fibromyomas in patients using exogenous hormones. This study has compared the mitotic activity of fibromyomas in three groups of patients. The first group was using a progestin-only preparation (usually depo-medroxyprogesterone acetate). The second group of age-matched controls had never used any exogenous hormone. The third group of patients was using a combined estrogen/progestin oral contraceptive. The results show that patients using a progestin-only preparation have a significantly higher mitotic activity in fibromyomas than patients from the other two groups; results from patients using a combined estrogen/progestin preparation were the same as the controls. The highest count was 39 mitoses/100 high power fields (HPF), but focal areas containing up to 8 mitoses/10 HPF could be found. In none of the fibromyomas examined did the count exceed 10 mitoses/10 HPF, and none showed significant pleomorphism that might have been confused with malignancy.

Androgen excess in cystic acne.

We measured hormone levels in 59 women and 32 men with longstanding cystic acne resistant to conventional therapy. Affected women had higher serum levels of dehydroepiandrosterone sulfate, testosterone, and luteinizing hormone and lower levels of sex-hormone-binding globulin than controls. Affected men had higher levels of serum dehydroepiandrosterone sulfate and 17-hydroxyprogesterone and lower levels of sex-hormone-binding globulin than controls. To lower dehydroepiandrosterone sulfate, dexamethasone was given to men, and dexamethasone or an oral contraceptive pill, Demulen (or both), was given to women. Of the patients treated for six months, 97 per cent of the women and 81 per cent of the men had resolution or marked improvement in their acne. The dose of dexamethasone required to reduce dehydroepiandrosterone sulfate levels was low, rarely exceeding the equivalent of 20 mg of hydrocortisone per day. We conclude that most patients with therapeutically resistant cystic acne have androgen excess and that lowering elevated dehydroepiandrosterone sulfate results in improvement or remission of acne in most instances.

Application of 125I-labelled second antibody to the solid-phase immunoassay of norethisterone in plasma.

The concept of employing 125I-labelled second antibodies for making quantitative measurements of small molecules in biological fluids was evaluated. In a model system 125I-labelled second antibodies were used to monitor the binding of purified norethisterone antibodies to albumin-norethisterone complexes immobilised upon plastic tube surfaces. Conditions were established to provide an assay response similar to other immunoassays for norethisterone using the same primary antiserum. The specificity and accuracy of the assay were comparable to the conventional solid and liquid-phase assays, but precision tended to be less at low levels of norethisterone (less than 200 pg/tube). A reduction in assay variance may be achieved through more efficient tube-washing procedures.

[Glucose tolerance on long-term treatment with a progestogen (etynodiol diacetate) (author's transl)]. / Glycorégulation et traitement progestatif au long cours (diacétate d'etynodiol).

Continuous long-term treatments with progestogens are able to bring about an hyperinsulinic reaction, which up till now has been considered to be due to a peripheral anti-insulin effect. Isolating the levels of immuno-reactive plasma insulin and of human C-peptide at the same time when loads of glucose and of tolbutamide are given after one another would seem to demonstrate that there is a primitive beta-islet of Langerhans origin for this hyperinsulinaemia. These results show that it is safe to prescribe etynodiol diacetate to "normal" patients as well as to "diabetic" patients.

Ovarian hyperandrogenism with normal and abnormal histologic findings of the ovaries.

Thirty-one patients with clinical features of polycystic ovary syndrome (PCO) were studied to determine the correlation between biochemical and histologic findings. The biochemical features investigated were the effects of adrenocortical and ovarian suppression by dexamethasone and oral contraceptives (Ovulen) on plasma free androgens. Four patients showed a histologic picture consistent with PCO (Group A), and five had histologically normal ovaries (Group B). The remaining 22 patients had no tissue available for histologic examination (Group C). The baseline values of plasma free testosterone (FTel) were higher and those of testosterone-binding globulin (TeBG) were lower (p less than 0.05) in Group A than in Group B, although plasma total testosterone (T) and the free 17beta-hydroxysteroid androgen index (FHSl) were similar in the two groups. During dexamethasone administration in all study groups, T and FTel fell slightly (17.7% to 33.8%), and FHSl levels decreased moderately (36% to 46.6%); in no case did both indices of free androgen levels fall to the normal range for dexamethasone-suppressed women. However, no change was noted in TeBG in all three groups. On the other hand, Ovulen treatment suppressed T and free androgens to normal in all groups, and raised TeBG more than 350% from the baseline. These data suggest a decrease in androgen production. The effects of dexamethasone and Ovulen on all three groups were similar in percent changes. As Group B patients resemble those of Group A biochemically and clinically, except for possibly being less hyperandrogenic, the concept of ovarian hyperandrogenism should be expanded to include patients with no anatomic ovarian abnormality, particularly in milder cases.