Effect of two oral contraceptives containing ethinylestradiol and gestodene or norgestimate upon androgen parameters and serum binding proteins

The effect of a triphasic oral contraceptive containing ethinylestradiol and gestodene (EE/GSD) on various serum hormonal parameters was compared with that of a monophasic formulation containing 35 μg ethinylestradiol and 250 μg norgestimate (EE/NGM). Blood samples were collected from 46 women on days 2, 11, and 21 of the preceding control cycle and of the third, sixth and twelfth treatment cycle. There was no significant difference in the influence on any hormonal parameter between both formulations. Both EE/GSD and EE/NGM caused a time-dependent suppression of serum dehydroepiandrosterone sulphate (DHEA-S) by 20–30% (p < 0.01) and a reduction of 5-androstane-3,17β-diol glucuronide by 50–60% (p < 0.01) during each treatment cycle, while androstenedione levels were reduced by 25% (p < 0.01). There was also a significant decrease in the levels of total testosterone by 30–35% (p < 0.01) and free testosterone by 60% (p < 0.01), while sex hormone-binding globulin (SHBG) was increased by 200–240% on days 11 and 21 (p < 0.01). During the pill-free interval the SHBG levels were reduced to a certain degree but remained elevated by 100% as compared to the pretreatment values. The serum levels of corticosteroid-binding globulin (CBG) which is known to be influenced only by the estrogenic component of combination pills, increased significantly by 170% (p < 0.01) during each treatment cycle. During the pill-free interval of 7 days, the CBG levels decreased but were still elevated by 90–100% as compared to the control cycle. Similarly, the serum levels of cortisol were significantly elevated by 110–140% (p < 0.01) during treatment with both preparations. The results demonstrate a profound suppression of androgen levels and peripheral androgen metabolism.     

Efficacy, cycle control, and side effects of low- and lower-dose oral contraceptives: a randomized trial of 20 μg and 35 μg estrogen preparations

Estrogen content represents a tradeoff between cycle control and side effects, but few direct comparisons of 20 and 30/35 μg preparations are available. To address this issue, we conducted a randomized, open-label multicenter clinical trial comparing Alesse® (20 μg ethinyl estradiol [EE]), Mircette® (20 μg EE), and Ortho Tri-Cyclen® (35 μg EE) among 463 OC starters or switchers.

Bloating, breast tenderness, and nausea were approximately 50% more common in women using 35 μg EE as compared to 20 μg EE preparations. Cycle control was similar in all products, although during the first two cycles among starters; users of Mircette and Ortho Tri-Cyclen (Tri-Cyclen) exhibited better cycle control than Alesse users. Discontinuation and pregnancy rates were not significantly higher in 35 μg EE users.     

Serum resistin levels in women taking combined oral contraceptives containing desogestrel or gestodene

Resistin is a hormone secreted by adipose tissue that could be involved in the development of insulin resistance. Previous studies confirmed that endogenous sex steroids may influence serum resistin concentration in women. The aim of our study was to investigate the influence of combined oral contraceptives containing desogestrel or gestodene on circulating levels of resistin. Fifty-three women were enrolled in the study. Thirteen patients received 20 μg ethinylestradiol/150 μg desogestrel, 15 women were treated with 20 μg ethinylestradiol/75 μg gestodene, 11 with 30 μg ethinylestradiol/150 μg desogestrel and 14 with 30 μg ethinylestradiol/75 μg gestodene. Blood samples for estimation of serum resistin and insulin levels were drawn before administration of oral contraceptive and after 6 cycles of therapy. We found that serum resistin level remained unchanged in women receiving ethinylestradiol/desogestrel and was reduced in women treated with formulations containing gestodene. We conclude that ethinylestradiol combined with desogestrel or gestodene is unlikely to induce insulin resistance through resistin pathway.     

Pharmacokinetics of 3-keto-desogestrel and ethinylestradiol released from different types of contraceptive vaginal rings

Pharmacokinetics of 3-keto-desogestrel and ethinylestradiol released from contraceptive vaginal rings (CVRs) with different release rates (75/15, 100/15 and 150/15 μg 3-ketodesogestrel/ethinylestradiol daily) were investigated in two studies in young healthy female volunteers. As reference, an oral preparation containing 150 μg desogestrel and 30 μg ethinylestradiol (Marvelon^R tablets) was also administered to the volunteers. To assess the disposition parameters of 3-ketodesogestrel and ethinylestradiol, some of the volunteers were additionally given an i.v. preparation containing 150 μg 3-ketodesogestrel and 30 μg ethinylestradiol.

Serum levels obtained with CVRs showed an initial increase during the first three days, followed by a plateau decreasing only slightly during the remainder of the treatment period. Mean plateau levels (± s.d.) of 3-keto-desogestrel were 2.3 ± 0.9, 2.8 ± 1.1 and 3.8 ± 1.1 pmol/ml for CVR 75/15, 100/15 and 150/15, respectively. Mean plateau levels of ethinylestradiol were 184 ± 75, 262 ± 102 and 233 ± 102 pmol/l, respectively. The in vivo release rates of 3-keto-desogestrel and ethinylestradiol from the CVRs were in good agreement with the in vitro release rates.

For both steroids the bioavailability from the CVRs was approximately 1.2 times higher than that from the tablets. The 3-keto-desogestrel serum levels were found directly proportional to the release rates within the range studied (75–150 μg/day). For ethinylestradiol the intra-individual variation in steady-state levels was too large to draw pertinent conclusions.     

Pituitary, ovarian and endometrial effects of 300 μg norethisterone and 30 μg levonorgestrel administered on cycle days 7 to 10

The ovarian, endometrial and pituitary effects of 300 μg norethisterone (NET) and 30 fig levonorgestrel (L-NOG) administered orally on cycle days 7–10 were investigated in two groups of 10 women each, by daily analysis of plasma estradiol (E₂), progesterone (PROG), immunoreactive luteinizing hormone (LH) and follicle stimulating hormone (FSH) in a pretreatment control cycle and during NET or L-NOG administration. Endometrial biopsies were obtained for morphometric analysis on cycle day 11 in the control and treatment cycles. Treatment with 300 μg NET resulted in an increase in the area under the E₂ peak (p<0.05), reduction in the number of subjects with normal progesterone profile (p<0.05) and a decrease in the area under the progesterone curve (p<0.05). The treatment suppressed the LH peak in 4 subjects and progesterone in 4 subjects. The follicular phase was prolonged in one subject, Norethisterone induced marked subnuclear vacuolation in the endometrium, while the glandular mitoses were decreased during NET treatment. Treatment with 30 μg L-NOG resulted in a decrease in subjects with normal progesterone profiles (p<0.05) and in the area under the progesterone curve (p<0.05). The treatment suppressed the LH peak in 3 subjects and progesterone in 4 women. The follicular phase was prolonged in one subject. L-NOG did not significantly increase the diameter of glands or induce subnuclear vacuolation in the endometrial glands.     

A 12-month clinical investigation with a 24-day regimen containing 15 μg ethinylestradiol plus 60 μg gestodene with respect to hemostasis and cycle control

The effects of a 24-day regimen containing 15 μg ethinyl estradiol (EE) plus 60 μg gestodene on cycle control and on hemostasis, were evaluated in 58 healthy women (age 19–47 years). All women received the pill for 12 months. Withdrawal bleeding at every cycle during the tablet-free interval was experienced by 84.5% of the women. The overall incidence of irregular bleedings was 19.3%. Hemostasis was evaluated in 20 women. No changes in plasma fibrinogen concentrations, nor in prothrombin fragment F1+2 were observed. A slight increase in thrombin-antithrombin III complexes was observed after 6 and 12 months of oral contraceptive use. Antithrombin III activity significantly increased after one-year of pill intake. The concentrations of tissue plasminogen activator and plasminogen activator inhibitor, both antigen and activity, did not change. These results show that very low doses of EE, such as 15 μg, do not impair hemostasis in healthy females. However, the reduction for the EE dose is responsible of some of the effects on cycle control.     

Hormonal effects of the 300 μg norethisterone (NET) minipill: 2. Daily gonadotrophin levels in 43 subjects during a pretreatment cycle and during the second month of NET administration

The peripheral plasma levels of immunoreactive follicle-stimulating hormone (hFSH) and luteinizing hormone (hLH) were measured daily in 43 normally menstruating women during a pretreatment (control) cycle and during the second month of daily administration of the 300 μg norethisterone (NET) minipill. In addition, the levels of biologically active LH were also determined in 29 of the 43 subjects.

As described in detail in the first paper of these series (1), the 43 women studied exhibited four distinctly different types of ovarian reaction to NET, as indicated by the daily estradiol and progesterone levels. Seven women (16 %) showed neither follicular, nor luteal activity (group A), 10 women (23 %) exhibited a cyclic follicular activity, but no luteal function (group B), 9 women (21 %) had normal follicular function, but insufficient luteal activity (group C), and 17 women (40 %) had estradiol and progesterone levels undistinguishable from those seen in a normal ovulatory cycle (group D).

Administration of the NET minipill did not influence the mean FSH lvel of cycle days 1–6, or those of 3 to 7 days before the LH peak; it slightly decreased the mean luteal phase FSH level in group C, but no in group D, and markedly suppressed the FSH peak value in all groups. There was no difference in this respect between women exhibiting different types of ovarian reaction. Similar to its effect on FSH, the administration of NET did not diminish the mean LH levels of days 1–6, those of 3 to 7 days before the LH peak, or of the luteal phase, but greatly suppressed the LH peak. Again, there was no difference in LH levels during NET administration among women showing different types of ovarian response to the drug. On the other hand, significant differences were found in the LH levels of the pretreatment (control) cycles of the various groups. The mean levels of LH both during days 1–6 and during the luteal phase of the pretreatment cycles were significantly lower in women in whom the minipill subsequently abolished all lutaeal activity (groups A+B) than in women exhibiting different degrees of luteal function (groups C+D). Hence the NET minipill will preferentially inhibit ovulation in women exhibiting relatively low tonic LH-levels in untreated cycles.

The results of the daily LH bioassays were in good agreement with those of the radioimmunoassays.

In the majority of women who exhibited normal (“ovulatory”) estradiol and progesterone profiles during NET administration, the preovulatory FSH, and especially LH peaks were below the lower limit of normal values, and in several instances, normal estradiol and progesterone profiles were found in the virtual absence of any FSH and LH surge.

It is concluded that ovarian suppression by the NET minipill is unrelated to the degree of inhibition of FSH and LH secretion as far as this is reflected by their peripheral levels measured daily.     

A randomized study over 13 cycles to assess the influence of oral contraceptives containing ethinylestradiol combined with drospirenone or desogestrel on carbohydrate metabolism

In this open-label, randomized study we compared the influence of a new oral contraceptive containing 30 μg ethinylestradiol and 3 mg drospirenone (Yasmin™) with a reference preparation containing 30 μg ethinylestradiol and 150 μg desogestrel (Marvelon™) on variables of carbohydrate metabolism by means of oral glucose tolerance tests at baseline and in the 6th and 13th treatment cycle. The mean levels of fasting glucose and insulin were similar at baseline and after 13 treatment cycles, whereas C-peptide and free fatty acid levels decreased slightly in both groups. All blood glucose and insulin values measured in the oral glucose tolerance tests were within normal ranges, despite a slight increase in the mean areas under the curves of 0–3 h [AUCs (0–3 h)] of both variables from baseline to treatment cycle 13. Differences between both treatments were not statistically significant. The mean AUCs (0–3 h) for C-peptide were not markedly changed in any treatment group. Free fatty acid levels decreased by 42% in the drospirenone group and increased by 48.9% in the desogestrel group, in terms of means of individual changes. Both preparations were well tolerated and equally efficacious regarding contraception and cycle control. The mean body weight was slightly decreased in most cycles during treatment with the drospirenone combination, as compared to baseline, while it was slightly increased versus baseline in all cycles during treatment with the desogestrel combination. The combination with drospirenone had less impact on blood pressure than the combination with desogestrel. In conclusion, Yasmin, a combined low-dose oral contraceptive with 30 μg ethinylestradiol and 3 mg of the novel progestogen drospirenone, as well as the reference Marvelon, containing 30 μg ethinylestradiol and 150 μg desogestrel had little impact on carbohydrate metabolism when used for 1 year. The observed changes were small and not suggestive of a clinically relevant deterioration of carbohydrate metabolism.     

Ovarian function during low-dose oral contraceptive use

Lowering the total steroid dose in modern oral contraceptives (OCs) has been connected with a higher incidence of ovarian follicle and cyst formation. To investigate the presence of ovarian follicles and cysts by means of vaginal ultrasonography and serum hormone determinations during use of two low-dose OCs, 65 volunteers were randomized to receive either 20 μg ethinylestradiol (EE) + 150 μg desogestrel (group A) or 35 μg EE + 250 μg norgestimate (group B) for a 2-month study period. At baseline, 39% of women in group A and 31% in group B exhibited at least one follicle <35 mm in diameter. By the end of the second treatment cycle, the frequency of these follicles had decreased to 14% in each group. Only one subject in the higher estrogen group developed an ovarian cyst >35 mm. One subject in each group demonstrated hormone levels characteristic of ovulation; no pregnancy occurred in either group. The 20 μg EE preparation was not found to lead more often to ovarian follicles or cysts when compared with a 35 μg EE preparation, possibly because of the type and dose of the progestogen used.     

Flaxseed consumption influences endogenous hormone concentrations in postmenopausal women

Lignans, similar in structure to endogenous sex steroid hormones, may act in vivo to alter hormone metabolism and subsequent cancer risk. The objective of this study was to examine effects of dietary intake of a lignan-rich plant food (flaxseed) on serum concentrations of endogenous hormones and binding proteins (estrone, estrone sulfate, 17 beta-estradiol, sex hormone-binding globulin, progesterone, prolactin, dehydroepiandrosterone sulfate, dehydroepiandrosterone, androstenedione, testosterone, and free testosterone) in postmenopausal women. This randomized, crossover trial consisted of three seven-week feeding periods, during which 28 postmenopausal women, aged 52-82 yr, consumed their habitual diets plus 0, 5, or 10 g of ground flaxseed. Serum samples collected during the last week of each feeding period were analyzed for serum hormones using standard diagnostic kits. The flaxseed diets significantly reduced serum concentrations of 17 beta-estradiol by 3.26 pg/ml (12.06 pmol/l) and estrone sulfate by 0.09 ng/ml (0.42 nmol/l) and increased prolactin by 1.92 micrograms/l (0.05 IU/ml). Serum concentrations of androstenedione, estrone, sex hormone-binding globulin, progesterone, testosterone, free testosterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate were not altered with flaxseed feeding. In this group of postmenopausal women, consuming flaxseed in addition to their habitual diets influenced their endogenous hormone metabolism by decreasing serum 17 beta-estradiol and estrone sulfate and increasing serum prolactin concentrations.     

Clinical comparative study of oral contraceptives containing 30 microg ethinylestradiol/150 microg levonorgestrel,and 35 microg ethinylestradiol/250 microg norgestimate in Thai women

The study was conducted to compare cycle control, efficacy and side effects of two oral contraceptives containing 30 μg ethinylestradiol (EE)/150 μg levonorgestrel (LNG) and 35 μg ethinylestradiol (EE)/250 μg norgestimate (NGM). An open-label, randomized, comparative study was conducted in which 140 healthy women received the 30 μg EE/150 μg LNG or 35 μg EE/250 μg NGM preparation for six treatment cycles. There were no significant statistical differences between both groups in terms of cycle length and amount of withdrawal bleeding. The mean duration in the 35 μg EE/250 μg NGM group was longer than 30 μg EE/150 μg LNG group with significant statistical difference. More patients in 35 μg EE/250 μg NGM group experienced BTT at each cycle compared with the 30 μg EE/150 μg LNG group, but was not statistically significant. There was no amenorrhea nor pregnancies occurring in either group. No significant changes in body weight or blood pressure were found in both groups. The incidence of adverse events in both groups was low and tended to decrease with time. Statistically significant differences were observed for headache and dizziness, which occurred more in the 30 μg EE/150 μg LNG group. In conclusion, 35 μg EE/250 μg NGM provides reliable contraceptive efficacy. It also provides good cycle control equal to 30 μg EE/150 μg LNG with a lower incidence of minor adverse effects such as headache and dizziness compared to 30 μg EE/150 μg LNG.     

A comparison of cycle control,efficacy, and side effects among healthy Thai women between two low-dose oral contraceptives containing 20 microg ethinylestradio1/75 microg gestodene (Meliane) and 30 microg ethinylestradio1/75 microg gestodene (Gynera)

The purpose of this study was to compare cycle control, efficacy and side effects of an oral contraceptive containing 20 μg ethinylestradiol and 75 μg gestodene, with a reference preparation containing 30 μg ethinylestradiol combined with 75 μg gestodene. From the study, it was demonstrated that the two regimens had no difference in cycle control, efficacy, and side effects. The occurrence of spotting and breakthrough bleeding was low and was not different between these two preparations. The most common adverse events in both treatment groups were nausea, vomiting, dizziness, and chloasma. There were no statistically significant change in body weight and blood pressure in both groups at the end of study. It is concluded that both preparations are good cycle control, reliable and low side effects oral contraceptives.     

Effects of oral ethinylestradiol on serum proteins in normal women

Daily oral doses of 10, 20, 50 and 75μg of ethinylestradiol were administered for three weeks to groups of normal healthy women. Changes in blood levels of albumin, ceruloplasmin, total iron-binding capacity, haptoglobin and orosomucoid were followed. The estrogen decreased serum albumin, haptoglobin and orosomucoid, increased ceruloplasmin, but had no effect on iron-binding capacity. There was no significant difference in these components between the 50 and 75 μg daily oral doses, and differences between 20 and 50 μg doses were small in most cases. The concurrent administration of 1.0 or 3.0 mg daily of norethisterone acetate with the 50μg daily dose of ethinylestradiol had little extra effect on the serum proteins, with the exception of total iron-binding capacity, which showed a marked increase.     

3-(4-Hydroxy phenyl)-2-propenoic acid — a reproductive inhibitor in male rat

Oral administration of 3-(4-hydroxy phenyl)-2-propenoic acid, at a dose of 50 mg/kg body weight/day (reported antiprolactin dose in rat) for 56 days, to adult male rat produces complete loss of libido, significant decrease in weight of testis and accessory sex organs, decrease in fructose content of coagulating gland and reduction in acid phosphatase activity in prostate. All these effects can be reversed by exogenous prolactin (500 μg/rat/day) plus testosterone propionate (200 μg/rat/day), but not by prolactin or testosterone alone, when administered along with the test compound for the last 28 days. Inhibitory influence of the compound over the reproductive organs is believed to be attributed primarily to the antiprolactin nature of the compound and secondarily to the significant (P<0.01) fall in plasma testosterone level caused by the compound.     

Effect of four different oral contraceptives on various sex hormones and serum-binding globulins

In a double-blind, controlled, randomized, four-arm, bicentric clinical study, the effect of four oral contraceptives (OCs) on various hormone parameters and serum-binding globulins was investigated. Four groups with 25 volunteers each (18-35 years of age) were treated for six cycles with monophasic combinations containing 21 tablets with either 30 microg ethinylestradiol (EE) + 2 mg dienogest (DNG) (30EE/DNG), 20 microg EE + 2 mg DNG (20EE/DNG), 10 microg EE + 2 mg estradiol valerate (EV) + 2 mg DNG (EE/EV/DNG) or 20 microg EE + 100 microg levonorgestrel (LNG) (EE/LNG). The study was completed by 91 subjects. Blood samples were taken after at least 12 h of fasting on Day 21-26 of the preceding control cycle and on Day 18-21 of the first, third and sixth treatment cycle. The serum concentrations of free testosterone were significantly decreased by about 40-60% in all four groups, while those of dehydroepiandrosterone sulfate (DHEAS) showed a time-dependent decrease during treatment. Except for EE/EV/DNG, which increased prolactin significantly during the third and sixth cycles, no change was observed with the EE-containing preparations. There was a significant increase in the levels of serum-binding globulins during treatment, which differed according to the composition of the OCs used. The rise in sex hormone-binding globulin (SHBG) was highest during intake of 30EE/DNG (+320%) and lowest with EE/LNG (+80%), while the effect of 20EE/DNG and EE/EV/DNG was similar (+270%). The thyroxine-binding globulin (TBG) levels increased significantly, by 50-60%, during treatment with the DNG-containing formulations, while the effect of EE/LNG was less significant (+30%). The rise in corticosteroid-binding globulin (CBG), which occurred in all groups, was most pronounced in women treated with 30EE/DNG (+90%) and least with EE/EV/DNG (+55%), indicating a strong influence of EE and no effect of the progestogen component. In all treatment groups, the frequency of intracyclic bleeding rose in the first treatment cycle and decreased thereafter. Cycle control was significantly better with 30EE/DNG or EE/LNG than with 20EE/DNG or EE/EV/DNG. There was no significant change in blood pressure, body mass index or pulse rate throughout the study. In conclusion, the DNG-containing OCs caused a higher rise in SHBG and TBG levels than the LNG-containing preparation. The effects on CBG suggest a lesser hepatic effect of 2 mg EV as compared to 20 or 30 microg EE. In contrast to EE, the use of estradiol in OCs appeared to increase prolactin release, while the cycle control was better with the OC containing 30 microg EE.     

Determinants of sex hormone levels in men as useful indices in hormone-related disorders

Because the determinants of serum sex hormone levels in men have been infrequently studied, we investigated the relation of several personal characteristics to serum levels of testosterone (T), dihydrotestosterone (DHT), estrone (El), estradiol (E2) and sex hormone-binding globulin (SHBG) among 98 Japanese American men in Hawaii, aged 52–74. The SHBG levels and T/(El + E2) ratios decreased progressively with increasing body mass index. The SHBG levels were also inversely associated with hematocrit levels. Serum androgen and estrogen levels did not correlate with smoking, alcohol intake, serum cholesterol, serum uric acid and blood pressure. Some of the associations observed in the present study may be implicated in the etiology of hormone-related neoplasms in men.     

‘Functional sterility’ in male rats after micro-dose estrogen treatment

Adult male rats were injected with estradiol dipropionate at the rate of 0.1, 1.0, 5.0, 50.0 and 100.0 μg daily for 15 or 30 days. Doses lower than 5 μg had no effect on spermatogenesis and fertility, but higher doses caused spermatogenic arrest and inhibition of libido. The minimum effective dose was found to be 5 μg/15 days which caused 100% reduction in fertility without disturbing spermatogenesis or libido. However, when the treatment period was extended for 30 days varying degrees of spermatogenic interruption and loss of libido were recorded. The mechanism of antifertility action is discussed.     

Plasma hormone levels in women receiving new oral contraceptives containing ethinyl estradiol plus levonorgestrel or desogestrel

The changes in plasma hormone levels were evaluated in matched healthy female volunteers investigated before and after 6 months' use of three new oral contraceptives (OCs): Trigynon^R (n = 13), a triphasic OC containing low doses of ethinylestradiol (EE) + levonorgestrel (LNg); Marvelon^R (n = 14), a monophasic OC containing low doses of EE + desogestrel (DOG, a new progestogen derived from LNg); and Ovidol^R (n = 10), a sequential OC containing higher doses (50 νg) of EE + DOG. Serum levels of FSH, LH, estradiol and progesterone were decreased in all cases to levels incompatible with ovulation. Prolactin concentrations were unchanged. Sex hormone binding globulin (SHBG) and Transcortin (CBG) levels were significantly increased by all three OCs (Ovidol>Marvelon>Trigynon); free testosterone levels decreased significantly while free cortisol concentrations remained unchanged.

Collectively, these data indicate that (a) all three OCs are effective ovulation inhibitors, (b) Ovidol and Marvelon have greater estrogenic effects than Trigynon, (c) LNg is more effective than DOG in reducing the EE-induced increase in SHBG levels, and (d) free testosterone levels are equally well suppressed by all three Ocs.     

Effects of an oral contraceptive containing 30 mcg ethinyl estradiol and 2 mg dienogest on thyroid hormones and androgen parameters: conventional vs. extended-cycle use

BACKGROUND: This study was conducted to investigate the effects of an oral contraceptive containing 30 mcg ethinyl estradiol and 2 mg dienogest on thyroid hormones and androgen parameters. STUDY DESIGN: Thyroid and androgen parameters were measured in 59 women treated with a monophasic combined oral contraceptive containing 30 mcg ethinyl estradiol and 2 mg dienogest (EE/DNG) either conventionally (13 cycles with 21 days of treatment+7 days without hormones) or according to an extended-cycle regimen (four extended cycles with 84 days of continuous administration of EE/DNG, followed by a hormone-free interval of 7 days). Blood samples were taken on Days 21-26 of the preceding control cycle and on Days 19-21 of the 3rd and 13th conventional cycle, or on Days 82-84 of the first and fourth extended cycle. RESULTS: At both time points, the serum concentrations of thyroxine-binding globulin were elevated by about 65% in both treatment regimens. Likewise, both groups showed an increase in total triiodothyronine (T3) and total thyroxine (T4) by 30-40%, and no change in free T4. Until the 12th month of conventional treatment, the level of free T3 remained unchanged but decreased slightly during the extended-cycle regimen. In both groups there was a rise of sex hormone-binding globulin by 210-230% after 3 months and by 220-250% after 12 months. The levels of total testosterone were reduced by about 40% and those of free testosterone by 55-65% after 3 and 12 months. CONCLUSION: The results suggest that, during conventional and extended-cycle treatment with EE/DNG, a steady state in the effects on thyroid hormones and androgen parameters was reached within 3 months and that the changes in the various hormonal parameters did not substantially differ between conventional and extended-cycle regimen.     

Levels of contraceptive steroids in breast milk and plasma of lactating women

Hormonal contraceptives have been used in breast feeding women by many clinicians. However, secretion of these drugs in the breast milk has not been adequately investigated. In the present study, radioimmunoassay methods were used for estimating the contraceptive drug levels in breast milk and plasma samples. In 7 lactating women, after the injection of 150 mg medroxyprogesterone acetate = MPA (Depo-Provera), MPA levels in breast milk were similar to plasma; the ratio being almost 1: 1 throughout the study period (up to 87 days). In a group of women using oral pills (2 women took a combination pill containing 150 μg d-norgestrel (d-Ng) and 30 μg ethinylestradiol, another 5 women took progestogen-only pills containi 350 μg norethisterone (NET)), the levels of d-Ng and NET in breast milk were about 1/10th or less than those found in plasma.