Plasma concentrations of endogenous hormones during one regular treatment cycle with a low-dose oral contraceptive and during two cycles with deliberate omission of two tablets

In this open, prospective, phase-I study we closely monitored levels of endogenous progesterone, 17β-estradiol, luteinizing hormone (LH) and follicle stimulating hormone in six healthy women. We determined plasma concentrations every 1–3 days during one untreated baseline cycle and during the first treatment cycle with regular pill intake of an oral contraceptive containing 30?μg ethinylestradiol plus 75?μg gestodene. During the following two treatment cycles, two tablets were deliberately omitted (in cycle 2 on days 6/7 and in cycle 3 on days 11/12). All but possibly one volunteer ovulated in the untreated pre-cycle, as concluded from LH peaks followed by marked increases of progesterone. During the regular first treatment cycle and even after deliberate omission of two tables in treatment cycles 2 and 3, the progesterone and estradiol levels remained low, so that we concluded that no ovulation took place. However, two volunteers showed some sort of LH peak in the first regular treatment cycle and all women showed LH increases of >?40?μg/ml in at least one omission cycle. In ten out of 12 cycles, omissions of pill intake were followed by an episode of intermenstrual bleeding. In conclusion, we have shown that, after omission of two consecutive oral contraceptive tables, the endogenous hormone parameters did not provide evidence for ovulation. Although this provides confirmation of the robustness of this oral contraceptive towards non-compliance, the widely published practical recommendations should be followed.     

Longitudinal ultrasonographic study of the ovarian suppressive activity of a low-dose triphasic oral contraceptive during correct and incorrect pill intake

A longitudinal study was conducted to evaluate the ability of a low-dose triphasic oral contraceptive to suppress ovulation as documented by frequent ultrasonographic scanning and progesterone determinations, even in the event of a missed pill. The extent of follicular growth and maturation, the incidence of escape ovulation, and the effect of correct and incorrect pill intake were assessed in 30 evaluable women during two consecutive spontaneous menstrual cycles. After the first cycle, 11 of 30 women (36.6%) had follicle-like structures of at least 10 mm in diameter. Ten of 11 structures gradually disappeared during the second cycle, with one persistent structure remaining through the second cycle. Seven of 30 women (23%) developed follicle-like structures during the second cycle. Of these, one woman had a probable ovulation, and another had an elevated progesterone level without follicle rupture, suggesting the luteinized unruptured follicle syndrome. Both of these women missed a pill on day 1 of the second cycle. In all cases cervical scores indicating hostility were noted. Thus, although suppression of ovarian activity may have been incomplete when oral contraceptives were incorrectly taken, secondary mechanisms of contraception remained operant. When they were correctly taken, low-dose triphasic oral contraception consistently prevented ovulation.     

Use of the novel combined contraceptive vaginal ring NuvaRing for ovulation inhibition

OBJECTIVE: To assess the effects of the combined contraceptive vaginal ring NuvaRing on ovarian function. DESIGN: Randomized, open-label, crossover study. SETTING: Clinical pharmacology unit. PARTICIPANT(S): Sixteen healthy female volunteers. INTERVENTION(S): Group 1: one cycle of combined oral contraceptive containing desogestrel (150 microg) and ethinyl estradiol (30 microg) (desogestrel/EE COC), followed by a NuvaRing treatment period. Group 2: NuvaRing treatment period followed by a cycle of desogestrel/EE COC. MAIN OUTCOME MEASURE(S): Follicular diameter, serum hormone concentrations (follicle-stimulating hormone, 17beta estradiol, luteinizing hormone, and progesterone), and endometrial thickness. RESULT(S): NuvaRing use for the recommended period of 3 weeks resulted in complete inhibition of ovulation, as assessed by vaginal ultrasound (follicular diameter) and by serum luteinizing hormone and progesterone concentrations. Inhibition of ovulation was maintained for an additional 2 weeks of NuvaRing use. Ovarian suppression between the groups was comparable. Furthermore, ovarian suppression after 3 weeks of NuvaRing use was comparable to that on day 21 of DGS/EE COC intake. NuvaRing was well tolerated. CONCLUSION(S): NuvaRing completely inhibited ovulation throughout the normal 3-week period and the extended period of use. Ovarian suppression was comparable to that with desogestrel/EE COC.     

Comparison of plasma hormone changes using a "conventional" and a "paper" pill formulation of a low-dose oral contraceptive

Two formulations of a low-dose oral contraceptive (Microgynon: 150 microgram of levonorgestrel [NG] +30 micrograms of ethynylestradiol [EE2]) were studied. The first was the "conventional" pill; the second was a "paper" pill prepared by evaporation of aliquots of a solution of the component steroids onto squares of edible cellulose separated by perforations, similar to a sheet of postage stamps. The effects of the two formulations on plasma levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17beta-estradiol (E2), and progesterone were compared. Samples of blood were obtained from five women during a treatment period on the "conventional" pill and from five on the "paper" pill. When possible, blood samples were also obtained from a "control" cycle of each of these female subjects. Plasma LH, FSH, E2, and progesterone levels were determined by specific radioimmunoassay methods during control and treatment periods and NG and EE2 levels during treatment periods. Eight-hour plasma profiles for NG and EE2 at the beginning and in the later stage of the treatment periods were obtained and these samples were also analyzed for LH, FSH, E2, and progesterone. Results showed that with one exceptcrogynon were equally effective in suppressing ovulation. As in a previous study, FSH levels appeared to be one of the most sensitive indices of suppression.     

Regulation of ovarian follicular and luteal function during treatment with exogenous gonadotropins in anovulatory infertility

The dosage, duration of treatment, and plasma hormone levels were analyzed statistically between and within groups of treatment cycles with (n = 46) and without (n = 10) ovulation. A significant difference was observed in the dosage of human menopausal gonadotropins (hMG) over various days of treatment, but not in the mean dosage of hMG and human chorionic gonadotropin (hCG) administered per cycle. Follicle-stimulating hormone (FSH):luteinizing hormone (LH) ratios, prolactin (PRL) levels, and the magnitude and the duration of the estradiol response were greater in the ovulatory cycles. Additionally, in the ovulatory cycles, the dose of hMG correlated with the plasma levels of estradiol, FSH, and LH, while in the anovulatory cycles, hMG dosage correlated only with the LH concentrations. After administration of hCG, the mean plasma concentrations of its beta subunit peaked within 1 day and remained detectable for up to 10 days thereafter. In the ovulatory cycles, the mean progesterone level was maximal 6 days following hCG administration. In these cycles, luteal phase progesterone levels correlated positively with the preovulatory estradiol and inversely with concentrations of the beta subunit of hCG. The data demonstrate that, in contrast to anovulatory follicles, ovulatory follicles were exposed to a relative "dominance" of FSH over LH, with higher concentrations of estradiol and PRL for several days before hCG was administered. Apart from hMG dosage, the endogenous discharge of LH appeared to be an important determinant of the ovarian response. A single 10,000 IU dose of hCG was adequate for inducing ovulation and maintaining luteal function.     

Ovarian consequences of the transient interruption of combined oral contraceptives.

The combined oral contraceptive pill is an efficient means of contraception. It acts at different levels of the genital tract. Despite its efficiency, it is universally suggested that patients take the pill at regular daily intervals. Little attention has been given to the question of what happens if you miss the pill one day or more. A study was undertaken to evaluate the consequences of pill misses at different times of the cycle. Forty-seven young, healthy, normally menstruating patients voluntarily enrolled. All were given Cilest (ethinyl estradiol 35 micrograms and norgestimate 250 mg, Cilag France) for 21 days without any misses. Then, after a 7-day interval, they were prescribed one (group 1), two (group 2), three (group 3) or four days of pill misses, to occur respectively on day 1 (group a), 6 (group b), 12 (group c) or 18 (group d) of a new 21 day cycle; supplementary contraceptive means were recommended. Four patients had no miss prescribed and served as controls. Ovarian function was evaluated with daily estrogen measurements (E1 + E2 enzymatic dosage, BioMérieux, France) and ultrasound examinations. When required, because of significant increase in estrogen or because of follicular growth detected on ultrasound, LH and progesterone were measured. None of the patients experienced a normal ovulation. Four patients (1 control, 1 from group 2a, and 2 from group 3a) had a significant increase in estrogen levels and had a follicular image on ultrasounds. One of them (group 3a) had a follicular rupture, but none had a LH surge or increase in progesterone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of a combined oral contraceptive containing 3 mg of drospirenone and 30 microg of ethinyl estradiol on the human endometrium.

OBJECTIVE: To provide an in-depth assessment of the effects of the combined oral contraceptive containing 30 microg of ethinyl estradiol and 3 mg of drospirenone (Yasmin, Schering AG, Berlin) on the endometrium by means of endometrial morphometry in comparison to an untreated cycle. DESIGN: The open, multicenter study consisted of one untreated precycle and 13 treatment cycles. SETTING: Four gynecologic clinics in Belgium, The Netherlands, and Switzerland were involved. PATIENT(S): Forty women with a history of regular menstrual cycles. INTERVENTION(S): Before the commencement of the trial, 3 months without any hormonal intake was obligatory. The first endometrial sample was done in the untreated precycle, adjusted to the day of LH peak plus 5 to 6 days. During the medication phase, endometrial samples were taken at cycle 3, 6 and 13. MAIN OUTCOME MEASURE(S): Primary outcome measure of the study was the morphologic assessment of the endometrium with measures such as glandular diameter, glandular epithelial height, and number of vacuolated cells per 1,000 glandular cells. Furthermore, the endometrial thickness was measured by ultrasound. RESULT(S): After 13 cycles of medication use the endometrium had an atrophic appearance in 63% of the subjects. The size of the glands, the glandular epithelial height, and the number of glands per square millimeter were already significantly reduced after 3 months' use. Histological and ultrasonographical evaluation of the endometrium indicated a suppression of the proliferative activity of the endometrium. CONCLUSION(S): The combination of 30 microg of ethinyl estradiol with 3 mg of drospirenone induces changes of the endometrium that are comparable with other combined oral contraceptives and exhibits a marked antiproliferative effect on the endometrium. The medication was proven to be an effective oral contraceptive and revealed good cycle control characteristics.     

Effects of clomiphene treatment on infertile women with normal menstrual rhythm

Summary. Fourteen infertile women with normal menstrual rhythm were investigated; each provided daily blood samples throughout two menstrual cycles: one control cycle and another on therapy with clomiphene (50 mg/day) given either from days 1 to 5 ( n =7; group I) or from days 5 to 9 ( n =7; group II) of the cycle. The effects of this empirical clomiphene therapy on the menstrual cycles were assessed by reference to the delay from termination of clomiphene therapy to ovulation (day after the LH peak) and by comparing pre-ovulatory oestradiol levels and luteal phase progesterone indices (total progesterone levels from days 4 to 8 post LH peak) in patients' control and treated cycles. No differences were observed in the effects of the treatment on the two groups of women except that the clomiphene to ovulation delay was greater in those treated earlier in the cycle (group I). Clomiphene caused increased follicular development as indicated by elevated pre-ovulatory oestradiol levels but this was not followed by improved progesterone indices. Ovarian ultrasonography indicated that the increased follicular development was in terms of numbers of follicles and not in maturity or oestrogen biosynthetic capacity of individual follicles. The lack of increased luteal progesterone levels thereafter indicated that mean luteal progesterone production per luteinized follicle was reduced. Clomiphene therapy as given in this study was therefore not successful in stimulating increased follicular/luteal hormone production from the dominant follicle/corpus luteum in such patients.     

The combined contraceptive vaginal device (NuvaRing): a comprehensive review.

OBJECTIVES: The aim of this study is to review the development of NuvaRing over the past decade to illustrate its use-effectiveness and acceptance as an alternative contraceptive option for women. METHODS: The data were extracted from the literature using computerised MEDLINE system. NuvaRing is a new combined hormonal contraceptive vaginal ring made of ethylene-vinyl-acetate copolymer, releasing 120 microg etonorgestrel and 15 microg ethinyloestradiol per day. This ring is inserted on any day from day 1 to day 5 of a menstrual cycle for 21 days, thereafter removed for 7 days ring-free period and discarded. RESULTS: Complete inhibition of ovulation is observed during treatment with this device. Clinical exposure to NuvaRing for 1786 women-years has resulted in 21 pregnancies, giving a Pearl Index of 1.18. Withdrawal bleeding (4.7-5.3 days) is regular (97-99% of cycles) with rare incidence of irregular bleeding (2.6-6.4%). The cycle control is good with the use of this combined contraceptive vaginal ring. NuvaRing is well tolerated and accepted by women as compared to oral pill. CONCLUSIONS: NuvaRing is an effective vaginal contraceptive option for women. However, further study is needed for monitoring its long-term effectiveness and impact on patient's quality of life since the NuvaRing is marketed in many countries.     

Effect of synthetic thyrotropin-releasing hormone on ovulation in baboons.

Twice daily oral thyrotropin-releasing hormone administered to female baboons throughout the menstrual cycle had no significant influence on cycle length or upon estrogen levels but produced blunted midcycle LH peaks and luteal phase progesterone levels in three fourths of the treatment cycles. Mean plasma prolactin levels were increased approximately 2.5-fold relative to untreated, ovulatory control cycles. CB-154 alone did not alter cycle length or endocrine parameters examined (mean prolactin levels were decreased but not significantly). Cycles during which CB-154 was administered concomitantly with TRH were characterized by normal ovulation as evidenced by luteal phase progesterone levels. Since the effect on LH secretion was reversed by concomitant CB-154 administration, TRH-induced anovulation in animals given long-term treatment appeared to be mediated through physiologic mechanisms sensitive to elevated circulating prolactin levels. However, this conclusion must be considered equivocal since prolactin levels were also elevated during ovulatory cycles following long-term TRH therapy. Finally, these data do no exclude the alternative possibility that anovulation in baboons given long-term TRH treatment was a reflection of thyroid disturbance and not directly attributable to elevated prolactin.     

Comparison of cycle control with a combined contraceptive vaginal ring and oral levonorgestrel/ethinyl estradiol

OBJECTIVE: The purpose of this study was to compare cycle control and tolerability of the NuvaRing (NV Organon, Oss, The Netherlands), a novel combined contraceptive vaginal ring, with a standard combined oral contraceptive pill. STUDY DESIGN: Healthy women aged 18 to 40 years who requested contraception received either NuvaRing or a combined oral contraceptive containing 30 microg ethinyl estradiol and 150 microg levonorgestrel for 6 cycles in 3 similarly designed studies. Each cycle comprised 3 weeks of ring or pill use, followed by 1 ring- or pill-free week. RESULTS: Two hundred forty-seven women began the studies, 121 women with NuvaRing and 126 women with the combined oral contraceptive. Withdrawal bleeding occurred in virtually all cycles in both groups. In the NuvaRing groups, the incidence of irregular bleeding was < or =5% in all cycles; this was lower than the combined oral contraceptive groups (5.4%-38.8%). Furthermore, the incidence of a normal intended bleeding pattern was significantly higher in the NuvaRing groups than in the combined oral contraceptive groups (P <.01). Both contraceptives were well tolerated. CONCLUSION: NuvaRing has excellent cycle control and is well tolerated.     

Comparison of TestPack and Ovustick for predicting ovulation

A study was designed to compare two methods of predicting the time of ovulation by detection of the urinary luteinizing hormone (LH) surge with two immunoassay kits designed for home use. A newly developed kit, TestPack, was compared with an existing kit, Ovustick. A group of 20 women with regular cycles were studied for one menstrual cycle. Ovulation was established with a serum LH surge and disappearance of the dominant follicle using transvaginal sonography followed by a rise in the serum progesterone level. In the 20 subjects, presumptive evidence of ovulation was obtained by determining the LH surge and the subsequent progesterone peak. In 18 of the 20, disappearance of the dominant follicle was also documented. Ovulation was predicted in 17 of the 20 subjects by both TestPack and Ovustick. Both tests were effective in predicting the day of ovulation, but TestPack provided a more easily defined end point and required less time and effort to perform.     

Inhibition of ovulation during discontinuous intranasal luteinizing hormone-releasing hormone agonist dosing in combination with gestagen-induced bleeding

Four groups of eight or nine normal cycling volunteers with regular menstrual cycles had daily blood sampling during two pretreatment, two treatment, and two posttreatment cycles. Intranasal doses of 100, 200, and 300 micrograms of (D-Ser[TBU]6-des-Gly-NH210) luteinizing hormone-releasing hormone (LH-RH) ethylamide were administered every 12 hours and compared with a 400-micrograms dose given every 24 hours during two periods of 21 days followed by a drug-free interval of 7 days. Five milligrams of medroxyprogesterone acetate was taken orally on days 17 to 21. Serum luteinizing hormone was elevated during the first 2 weeks of treatment, and serum follicle-stimulating hormone was increased only during the first 2 days of treatment. At 100 to 300 micrograms/12 hours serum estradiol was stimulated up to preovulatory levels, whereas at 400 micrograms/24 hours most values were in the early follicular phase range. Ovarian ultrasonography revealed the transient development of preovulatory-like follicles in 8 of 12 studied cycles. Serum progesterone values were less than 2 ng/ml in 57.3%, between 2 and 5 ng/ml in 27.9%, and greater than 5 ng/ml in 14.7%. Withdrawal bleeding occurred during the pause in 97% of treatment cycles. Nine of 13 breakthrough bleedings happened in the groups given 100-micrograms and 300-micrograms/12 hours. Recovery cycles showed slightly prolonged follicular phases with normal luteal phases. No changes were observed in routine laboratory measurements. In conclusion, intermittent administration of appropriate LH-RH agonist dosing in combination with a progestogen would effectively block ovulation while preserving adequate cyclic estradiol secretion and could be an alternative contraceptive approach.     

Endocrine modifications associated with final oocyte maturation with gonadotropin-releasing hormone agonists vs. human chorionic gonadotropin in women undergoing intrauterine insemination

OBJECTIVE: To compare the hormonal profile when using triptorelin vs. human chorionic gonadotropin (hCG) to trigger ovulation in intrauterine insemination (IUI) cycles. STUDY DESIGN: Twenty-five patients who underwent 48 cycles were enrolled in a prospective, randomized, crossover study. After ovulation induction with recombinant follicle-stimulating hormone (FSH), couples were randomly allocated to a first cycle with a single dose of 0.2 mg of triptorelin or 5,000 IU of urinary hCG to trigger ovulation; if pregnancy did not occur, a second cycle was carried out, and the patient was crossed over to the other treatment group. Blood was collected the day of hCG/triptorelin administration and both days after IUI. RESULTS: Patients treated with triptorelin showed a significantly higher FSH and luteinizing hormone (LH) rise 24 hours after the injection when compared to hCG. Serum progesterone was significantly increased 48 hours after hCG administration, although estradiol levels were comparable between the groups. CONCLUSION: A higher LH and FSH peak than that induced by hCG was observed. Considering that serum progesterone levels were suboptimal in both protocols and taking into account the lower progesterone production in gonadotropin releasing hormone analogue cycles, corpus luteum supplementation in the luteal phase should be recommended for these patients.     

Pituitary gonadotropins during long-term Enovid therapy

4 patients receiving the oral contraceptive Enovid, 5 mg tablets Day 5-24 of the treatment cycle, were studied for 7 cycles after therapy for a minimum of 12 and a maximum of 31 (mean duration of 25) consecutive months of therapy. In addition 1 patient was studied for a control cycle before receiving medication and a second cycle while on medication. Total gonadotropins and luteinizing hormone (LH) were determined on 24 hour specimens. There was a slight depression of total gonadotropins in the patients receiving long-term cyclic therapy. The results of the LH excretion studies showed no evidence of a midcycle peak in the patients on medication. It was suggested that the loss of the midcycle LH peak and generally diminished total gonadotropin levels might be adequate explanation for ovulation suppression by Enovid.     

A comparative study on the effects of a contraceptive vaginal ring NuvaRing and an oral contraceptive on carbohydrate metabolism and adrenal and thyroid function.

OBJECTIVES: To compare carbohydrate metabolism, adrenal and thyroid function during use of a combined contraceptive vaginal ring (NuvaRing, NV Organon, Oss, The Netherlands) with those of a combined oral contraceptive. METHODS: Healthy women aged 18-40 years used either the vaginal ring, delivering 15 microg ethinylestradiol and 120 microg of etonogestrel per day, or a combined oral contraceptive containing 30 microg ethinylestradiol and 150 microg levonorgestrel, for six cycles. Each cycle comprised 3 weeks of use of the ring or the pill followed by 1 ring- or pill-free week. The following parameters were measured at baseline and at the end of cycles 3 and 6: carbohydrate metabolism (glucose, insulin, glycosylated hemoglobin); adrenal function (total cortisol, cortisol binding globulin, dehydroepiandrosterone sulfate); thyroid function (thyroid stimulating hormone, free thyroxine). RESULTS: Small and similar increases in insulin were seen in both groups. Concentrations of cortisol binding globulin and total cortisol rose significantly less during ring use than during combined oral contraceptive use (cycle 3, p= 0.0002; cycle 6, p < 0.0001). Levels of dehydroepiandrosterone sulfate did not change in either group. Thyroid stimulating hormone levels increased significantly more in the ring group at cycle 3 (p = 0.0016) but free thyroxine levels were unchanged in both groups. CONCLUSIONS: Both the vaginal ring and the oral contraceptive have no clinically relevant effects on carbohydrate metabolism, adrenal or thyroid function.     

Enhanced pre-ovulatory progesterone levels in fertile cycles during clomiphene citrate treatment

We compared ovulatory changes in fertile and preceding infertile cycles in 21 patients with unexplained infertility conceiving after clomiphene citrate treatment. No significant differences were observed in follicular growth, cervical score and follicle stimulating hormone (FSH) levels. Progesterone was higher (P less than 0.05) in the 2 days preceding ovulation in fertile cycles, luteinizing hormone (LH) higher (P less than 0.05) the day before, and 17-beta-estradiol lower (P less than 0.05) 4 days before. Stimulating progesterone secretion by systematic LH administration before ovulation could improve secretory endometrial transformation and thus reproductive prognosis.     

A case of autoimmune progesterone dermatitis in an adolescent female

BackgroundProgesterone-induced dermatitis is a rare disorder. It typically occurs in females due to an autoimmune phenomenon to endogenous progesterone production, but can also be caused by exogenous intake of a synthetic progestin. Here, we present a case of autoimmune progesterone dermatitis (AIPD) seen in an adolescent female.CaseThe patient is a 15-year-old Caucasian female with no significant past medical history and no prior exogenous hormone use, who presented to her primary care physician complaining of cyclic skin eruptions. She noted that her dermatologic symptoms occurred monthly, just prior to her menses. An intradermal skin test using 0.1 cc of progesterone was performed. The patient immediately developed a wheal, confirming the diagnosis of AIPD. The patient was begun on a continuous regimen of an oral contraceptive pill with 30 micrograms of ethinyl estradiol and 0.15 mg of levonorgestrel. The skin eruptions have not returned since the initiation of this therapy.ConclusionAutoimmune progesterone dermatitis manifests via the occurrence of cyclic skin eruptions. Women with the disorder commonly present with dermatologic lesions in the luteal phase of the menstrual cycle. Diagnosis of AIPD is confirmed by performing a skin allergen test using progesterone. Due to its rarity, AIPD should be considered a diagnosis of exclusion.In cases believed to be due to an endogenous production of progesterone, several methods of therapy have been attempted. The ultimate goal of therapy is the suppression of ovulation, which will prevent endogenous hormone production as progesterone is only produced in ovulatory cycles. Currently, the first-line choice of therapy is a combination oral contraceptive. If this treatment is ineffective, patients have been treated with danazol, gonadotropin releasing hormone analogs, tamoxifen, and oophorectomy with varying success.     

Serum follicle-stimulating and luteinizing hormone and progesterone in single and multiple gestations following induction of ovulation

At the Mount Sinai School of Medicine in New York, researchers followed serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and progesterone in 5 women treated with human menopausal gonadotropin (HMG) and human chorionic gonadotropin (HCG) for induction of ovulation. A total of 7 treatment cycles were followed. In 5 of the cycles conception occurred. Values in the 5 cycles in which conception occurred were dissimilar to values in normal menstrual cycles. Thus, efforts to mimic normal gonadotropin elaboration are probably unnecessary in the treatment of anovulatory women. Significant variation in values occurred among the patients. A midcycle FSH peak concomitant with the LH surge was clearly seen to be unnecessary for ovulation induction. Following ovulation a general decline in FSH occurred. FSH apparently was suppressed during the gestational period. In patients who had elevated pretreatment serum LH levels, LH apparently was suppressed during the first 1/2 of the HMG therapy; however, during the latter 1/2 of the HMG therapy, LH rose in these patients. Therapy-induced multiple ovulation with resultant multiple corpora lutea caused serum progesterone levels to rise to 2-3 times those of normal singleton gestations. Implantation appeared to have occurred 8-9 days after ovulation induction. The 5 pregnancies resulted in 3 term deliveries, 1 first-trimester spontaneous abortion, and a quadruplet premature delivery.     

Contraceptive mechanism of microdose norethindrone

To determine how microdose progestogens exert their contraceptive mechanism, 5 normal 20-40 year old women (each acting as her own control) were studied during a normal menstral cycle followed by a cycle in which each received orrally 350 mcg norethindrone per day beginning on Cycle Day 1 for 30 days. Results indicated that all control cycles were ovulatory. In the treated cycle, endometrial morphology was altered. There was also significant suppression of preovulatory FSH and LH peaks, alteration of urinary estrogens (either increase or decrease), and marked suppression of progesterone production during the luteal phase. Cervical mucus properties and sperm penetration were inhibited during the treatment cycle. These findings suggest that at least 3 different factors were involved in the contraceptive mechanism of microdose norethindrone: 1) alteration of ovulation and progesterone production by the corpus luteum, 2) cervical mucus changes and inhibition of sperm transport, and 3) endometrial changes.