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Medroxyprogesterone acetate (MP) and norethindrone enanthate (NET) are used as depot preparations. Intramuscular injections of 150 mg MP are given every 12 weeks, and NET is administered in 200 mg dosages every 8 weeks for the first 4 intervals and every 12 weeks thereafter. These preparations prevent conception by inhibiting gonadotropin secretion (preventing ovulation), by making the cervical secretions impenetrable to sperm, and by affecting the endometrium to prevent nidation. The Pearl Index for these preparations when properly administered is less than 1. The most common side effect of using these preparations is menstrual irregularities; 71% of MP users and 47% of NET users never experience even 1 normal menstrual cycle per year. 35% of MP users and 9% of NET users do not experience a menstrual bleeding between the injections. Headache, depression, and leg cramps are other side effects of these preparations. Normal menstruation is observed about 8 months after discontinuing MP use and 3-6 months after NET use. These preparations do not affect lactation.
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PMID:[Depot gestagens as contraceptives]. 738 96

The capability of an early second injection or prior use of oral contraceptives (OCs) to improve satisfaction and long-term continuation of Depo-Provera in adolescents was investigated in a clinical trial involving 78 females 12-20 years of age (average, 15.9 years) recruited from a hospital-based adolescent health clinic. 36 subjects received injection of 150 mg of Depo-Provera every three months (Group 1), 27 received the second injection after only six weeks (Group 2), and 15 switched directly from OCs to the standard Depo-Provera regimen (Group 3). There was no difference between Groups 1 and 2 in terms of duration or frequency of menstrual bleeding; however, prior OC users experienced a significant reduction in the duration and intensity of bleeding in the first six months of Depo-Provera use (when estrogen was still present in the women's systems). Overall, 64% of study subjects reported less dysmenorrhea while on Depo-Provera. A slightly greater change in body mass index was observed among girls in Group 2 than in Groups 1 and 3; moreover, 70% of those in the early injection group reported increased appetite and weight gain compared to 39% of those on the standard schedule. The most commonly reported side effects included initial pain and soreness at the injection site (27%), decreased libido (56%), mood changes (31%), depression (26%), frequent headache (25%), fatigue (24%), and increase in acne (15%); there were no significant differences by group. 17 adolescents (22%) discontinued Depo-Provera, generally after two injections and due to bleeding irregularities or weight gain. 87% of adolescents who were prior OC users, 52% of those on the regular schedule, and 39% of those who received an early injection stated they were very satisfied with Depo-Provera. These findings indicate that early second Depo-Provera injection offers no advantages; use of OCs immediately prior to Depo-Provera should be further investigated, however, given its potential to minimize bleeding problems.
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PMID:Depo-Provera in adolescents: effects of early second injection or prior oral contraception. 766 88

In this report, we present the symptoms, biochemical investigations, 24 hour ambulatory blood pressure and heart rate recordings in a patient before and following removal of a predominantly adrenaline-secreting phaeochromocytoma. The symptoms were of episodic shaking, faintness, nausea, palpitations, sweating and panic, chest and neck pain with headache, and are consistent with previous reports. Ambulatory blood pressure recording demonstrated that mean daily blood pressure was normal, with normal diurnal variation, and two episodes of severe hypertension and bradycardia coincident with symptoms (MAP 150 mmHg and HR 49 beats/minute, MAP 178 mmHg and HR 29 beats/minute, respectively), not reported in predominantly adrenaline-secreting phaeochromocytoma.
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PMID:Twenty-four hour ambulatory blood pressure and heart rate in a patient with a predominantly adrenaline secreting phaeochromocytoma. 793 55

Progesterone, the natural progestogen produced by the corpus luteum, changes the endometrium from proliferative to secretory. In early pregnancy, progesterone maintains the pregnancy until the placenta develops and assumes hormonal production. It stimulates mammary gland development, suppresses contractility of the uterus, and inhibits T-lymphocyte production, thereby preventing immunological fetal rejection. Progesterone also causes an increase in renal sodium retention in nonpregnant women, stimulates the appetite, and increases the blood glucose level. It has a few minutes half-life in the blood. Progestins are synthetic progestogens. Health care providers must have a general understanding of progestogens in order to use them safely and effectively in practice. The author discusses selective information on them, what they are, how they act, properties, and concerns related to effects. The focus is upon progestogens used in combined oral contraceptives and hormonal replacement therapy. Major concerns exist about potential untoward lipoprotein changes, carbohydrate metabolism alterations, and breast cancer. Other concerns are associated with coagulation effects, prostacyclin changes, sex hormone-binding globulin capacity, psychological disturbances, blood pressure alterations, breakthrough bleeding, headaches, and other side effects. These preparations have, however, evolved over the years into safer formulations with fewer apparent risks.
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PMID:Progestogens: a look at the "other" hormone. 827 90

38 women aged between 23 and 42 years had secondary amenorrhea and clinical hypoesterogenism as assessed by the failure to have a withdrawal bleed in response to a progestin. All women were initially treated with up to 7.5 mg bromocriptine but it was discontinued because of failure to lower serum prolactin (PRL) or intolerance. Each woman had a basal computerized tomography (CT) scan before estrogen (E) replacement therapy, which was repeated after 6 months, and then yearly. The clinical course was monitored at 3-month intervals for the first year and the yearly. The patients were classified by CT scan as having either idiopathic hyperprolactinemia (19 patients), microadenoma (18 patients), or macroadenoma (1 patient). All patients have been followed with continuous exogenous E therapy for 2 to 6 years. The serum PRL was measured as a single random value by a double antibody homologous radioimmunoassay. 29 received physiological replacement with conjugated E (.625 mg, Premarin) from days 1 to 25 of each month, and added medroxyprogesterone acetate (10 mg, Provera) from days 16 to 25 of each month for 4.0 +or- 1.2 years. There was a significant decrease of serum PRL, and monthly withdrawal bleeding occurred in all women with alleviation of E-deficiency symptoms. 9 patients were treated with OCs for 2.0 +or- .8 years. There was a downward trend in the serum PRL without statistical significance. With abnormal CT scans, 6 patients with microadenomas had a decrease in size, whereas the remainder were unchanged. The patient with the macroadenoma (patient 29) had an onset of headaches after 4 months of therapy, but there was no change in the size of the tumor. The patients with normal CT scans did not show any change. The microadenomas in 2 of 3 women decreased in size. In summary, E-replacement therapy may be given to women with E deficiency, despite the presence of pathological hyperprolactinemia, as the induction of rapid growth of an underlying pituitary adenoma was not confirmed.
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PMID:The safety of physiological estrogen plus progestin replacement therapy and with oral contraceptive therapy in women with pathological hyperprolactinemia. 845 75

The US Food and Drug Administration finally approved the injectable contraceptive Depo-Provera (DMPA) in October 1992, 25 years after its introduction. Women return to a health facility every 90 days for an intramuscular injection of 150 mg DMPA, which provides them 99% effective contraception. Menstrual changes and spotting are the leading reasons for DMPA discontinuation. Eventually, more than 50% of DMPA users develop amenorrhea. During the first year, women gain about 2 kg and weight increases as time passes. Weight gain is the second leading reason for DMPA discontinuation. DMPA may adversely affect glucose tolerance in women at risk for diabetes, but it does not affect cardiovascular or metabolic functions. It may increase the risk of osteoporosis. A rare side effect is convulsions. 1-10% of DMPA users have other central nervous system effects, such as headaches, dizziness, and depression. Itching and rashes may develop. Fertility returns within 1 year after discontinuation. DMPA is linked to low birth weight. It apparently does not harm breast-fed infants or hinder lactation. A World Health Organization study shows that DMPA users less than 35 years old experience a slight increase in breast cancer but a reduced incidence of endometrial cancer. Nurses are instrumental in guiding women as they choose DMPA and in informing them about its potential side effects, including breast cancer risk. They must screen women for pregnancy and evaluate their risk of breast cancer. They must determine whether women are able to return every 3 months for DMPA injections. Women who select DMPA must use other contraception, e.g., barrier protection, within the first 24 hours after initial injection. Nurses should counsel them about the likely menstrual changes to reduce the likelihood of dissatisfaction. They should recommend a daily dose of 1200 mg of elemental calcium and daily exercise of long bones to minimize the risk of developing osteoporosis.
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PMID:Depo-Provera. 849 47

A leading patient complaint is headaches which tend to occur more often in women than men. Nonvascular headache is the most common and is caused by tension or muscle contraction. Oral contraceptives (OCs) do not affect nonvascular headaches. They can also be safely used in women who experience common migraines whose symptoms do not become more severe or frequent during OC use. On the other hand, women who have classic migraine (headache accompanied by focal neurologic symptoms) or common migraine with symptoms becoming more severe or frequent during OC use should discontinue OC use. Instead, they should use a barrier method or the IUD. Estradiol treatment appears to be effective in treating menstrual migraine. Since the data are inconclusive about the effect of OCs on young women who have experienced a stroke or transient ischemic attacks, it would be best for them to use a barrier method. Most antiepileptic drugs (phenobarbital, phenytoin, paramethadione, and carbamazepine) cause enzyme induction which may be linked to decreased levels of estrogen and increases in irregular bleeding, thereby increasing the likelihood of an epileptic OC user becoming pregnant. Possible contraceptive failure exposes a developing fetus to the teratogenic properties of the antiepileptic drugs. Thus, physicians should prescribe OCs with 50 mcg of ethinyl estradiol rather than 35 mcg ethinyl estradiol. Epileptic women can also use Depo-Provera, because it is not only effective in preventing pregnancy but reduces seizure frequency. It is important for any contraceptive method chosen for epileptic women to be effective because pregnancy intensifies seizures which in turn can damage the mother and/or fetus and cause neonatal distress.
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PMID:Contraceptive methods for women with neurologic disorders. 851 48

1. The effects of progesterone, its A-ring-reduced metabolites, allopregnanolone, tetrahydroxydeoxycorticosterone and the synthetic neuroactive steroid alphaxalone were evaluated in a rat model of plasma extravasation within the meninges following unilateral electrical stimulation (ES) of the trigeminal ganglion (0.6 mA, 5 ms, 5 min) or substance P administration (1 nmol kg-1, i.v.). 2. When administered 55 min prior to electrical stimulation, progesterone (> or = 500 micrograms, s.c.) dose-dependently decreased plasma extravasation within the meninges (ED50: 650 micrograms) but not within conjunctiva and tongue. Promegestone (R5020), a non-metabolized progesterone agonist (1000 micrograms, i.p.) was ineffective. The administration of progestrone (> or = 500 micrograms s.c.) 55 min prior to substance P partially suppressed plasma extravasation within the meninges (ED50: 550 micrograms). 3. The GABAA-antagonist, bicuculline (ED50: 8.2 micrograms kg-1, i.p.) but not the GABAB-antagonist, phaclofen (100 micrograms kg-1, i.p.) attenuated the effects of progesterone after electrical stimulation and substance P administration. 4. The metabolites of progesterone, allopregnanolone (3 alpha-hydroxy-5 alpha- pregnan-20-one (THP); ED50: 0.58 micrograms kg-1, i.p.), tetrahydroxydeoxycorticosterone (3 alpha,21- dihydroxy-5 alpha-pregnan-20-one (THDOC); ED50: 1.2 micrograms kg-1, i.p.) as well as the synthetic steroid alphaxalone (3 alpha-hydroxy-5 alpha-pregnane-11,20-dione; ED50: 1.8 micrograms kg-1, i.p.) suppressed plasma extravasation dose-dependently following ES, whereas the epimer of allopregnanolone, 3 beta-hydroxy-5 alpha-pregnan-20-one (100 micrograms kg-1, i.p.), did not. Extravasation caused by SP administration was partially suppressed by allopregnanolone (> or = 1 microgram kg-1, i.p.) (ED50: 2.1 micrograms kg-1). 5. The effect of progesterone (1000 micrograms, s.c.) and allopregnanolone (100 micrograms kg-1, i.p.) on neurogenic plasma extravasation was reversed by bicuculline (10 micrograms kg-1, i.p.) or by a congener, bicuculline-methiodide (10 micrograms kg-1, i.p.) which does not cross the blood brain barrier. 6. Progesterone (1000 micrograms, s.c.) had no effect on mean arterial blood pressure or heart rate when measured for 60 min after administration. 7. These results indicate that neurosteroid modulation of a GABAA-receptor located outside the blood brain barrier suppresses neurogenic and substance P-induced plasma extravasation within the meninges. The findings are consistent with previously reported data showing that valproic acid and muscimol inhibit meningeal oedema by bicuculline-sensitive mechanisms. Drugs which activate GABAA-receptors and its modulatory sites might be clinically effective in the treatment of migraine and cluster headache.
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PMID:GABAA-receptor-mediated effects of progesterone, its ring-A-reduced metabolites and synthetic neuroactive steroids on neurogenic oedema in the rat meninges. 882 49

The authors present their findings from the study of adolescents' reasons for discontinuing the use of Norplant and Depo-Provera. Their experiences after method discontinuation were also assessed. 35 adolescents of mean gynecologic age 4.7 years and body mass index (BMI) 24.2 who discontinued Depo-Provera, and 31 adolescents of mean gynecologic age 3.4 years and BMI 24.1 who discontinued Norplant were periodically assessed during use of the methods and up to 12 months after discontinuation. The most common reasons for discontinuation of both Norplant and Depo-Provera after mean periods of 21.8 and 9.2 months use, respectively, were irregular menstrual bleeding (64%), weight gain (41%), and increased headaches (30%). The resumption of menstrual regularity and dysmenorrhea was noted sooner after discontinuation of Norplant, compared to Depo-Provera. The increase in BMI noted at the discontinuation of Depo-Provera persisted up to 6 months after discontinuation of either method. 62% of adolescents reported no break in contraceptive practice. The condom was the most popular method (37%) after discontinuation of Depo-Provera, and oral contraceptives (39%) after discontinuation of Norplant. The authors conclude that health care providers should aggressively manage physical problems associated with Depo-Provera and Norplant use, and expedite the transition to new contraceptive methods in an effort to minimize the high pregnancy rates observed after discontinuation of these methods in adolescents.
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PMID:Adolescents' reasons for and experience after discontinuation of the long-acting contraceptives Depo-Provera and Norplant. 886 83

US teenagers have had access to the injectable contraceptive depot medroxyprogesterone acetate (DMPA; Depo-Provera) since the US Food and Drug Administration approved it in 1992. DMPA suppresses follicle stimulating hormone and luteinizing hormone (LH) levels, which in turn prevents the LH surge and thus inhibits ovulation. It also causes a thick cervical mucus (reducing sperm penetration). Since DMPA also changes tubal mobility and creates shallow and atrophic endometrium, implantation is prevented. DMPA must be administered every 3 months to be effective. Its first-year failure rate is 0.3%, which is lower than that of oral contraceptives (3%). Advantages of DMPA are that it: allows for privacy; improves compliance (since action is required every 3 months rather than every day); has no estrogen-related complications (e.g., thrombophlebitis); is effective; is safe for breast feeding teenagers; reduces seizure frequency in teenagers with epilepsy; has a favorable effect on sickle cell disease or coagulopathy; reduces menstrual flow, thus preventing iron-deficiency anemia; reduces menstrual pain and pre-menstrual symptoms; and decreases risk of pelvic inflammatory disease. The leading disadvantages are menstrual irregularities and spotting. Some other possible disadvantages include weight gain (most common reason for discontinuation), delayed return of fertility, headaches, acne, and nervousness. Health providers must perform a complete history of teenagers requesting DMPA. They should determine the presence or absence of absolute and relative contraindications to DMPA. Absolute contraindications are known or suspected pregnancy, undiagnosed or abnormal vaginal bleeding, known or suspected history of breast cancer, acute liver disease or jaundice, thromboembolism, and sensitivity to DMPA. DMPA is administered intramuscularly at a concentration of 150 mg/ml. Health providers need to use a frank, nonjudgmental, empathic, and unhurried approach to facilitate a trusting relationship and rapport with teenagers. Advanced counseling on the pros and cons of DMPA, how DMPA works, and DMPA's inability to protect against sexually transmitted diseases is essential.
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PMID:Use of depo-provera in teens. 892 Mar 51


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