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Pharmacology of the contraceptive steroids
Baby Hormones Hormones and Fetal Pathophysiology Edited by Jorge R. Pasqualini and Robert &holler. New York, Marcel Dekker, 1992, $185.00
(xiii + 808 pages),
ISBN-O-8246-8651-3. contains 14 multi-authored chapters covering the effects of hormones, growth factors, and proto-oncogenes on fetal development. The chapters are comprehensive, well written, and authored by acknowledged experts. The editors intended the book to be useful to obstetrician-gynecologists, neonatologists, pediatric endocrinologists, physiologists, and others interested in fetal growth and development. The book begins with two chapters on the fetal adrenal. However, it might have been more logical to begin with chapter 2, “Physiopathology of the Fetal Adrenal,” rather than with chapter 1, “Inborn Errors of Steroidogenesis.” Both chapters, however, are excellent in their coverage of these subjects. Chapters 4, 5, and 6 deal with sex differentiation. Dr. Josso’s chapter on anti-Mullerian hormone and Dr. Simpson’s review of disorders of sex differentiation are well worth reading. However, three chapters on sex differentiation may be more than are needed, and I found some information to be repetitive. Following these are three chapters on the physiopathology of the placenta. Chapter 8 by Drs. Casey and MacDonald on steroid production in the placenta is absolutely clear, concise, and comprehensive. Chapter 12 by Dr. Ojasoo et al. addresses the effects of prenatally administered sex steroids on the fetus. This chapter tends to be encyclopedic in its approach and is disappointing in that it does not include the issues of the effects of prenatal sex steroids on behavior and gender identity in humans. The real highlight of this book is chapter 13,“Proto-Oncogenes in Fetal Life.” This chapter deals with the molecular biology of proto-oncogenes in the fetus. The author, Dr. Swaneck, assumes correctly that some readers might not be familiar with the techniques and terminology of molecuHormones and Fetal Pathophysiology
262
lar biology. Therefore the first third of the chapter is a very well written, comprehensive, and informative primer on molecular biology, which makes the rest of the chapter clear even to the nonmolecular biologist. Probably because it is multi-authored and rather long, this is a difficult book to read in its entirety. Chapters of particular interest should be selected by the reader. The absence of a chapter on thyroid hormone synthesis and fetalmaternal thyroid relationships is a serious omission in this book. Also, I am disappointed by the scarcity of information on gonadotrophins, human chorionic sommatomammotrophin, and
growth hormone in relationship to fetal growth and development. After reading this book, I had learned a lot; however, I did not feel that I had a complete understanding of the effect of hormones on the fetus and its development in utero. This is a valuable text for its intended readership, and I recommend that it be available for reference purposes in hospital and medical school libraries. TEM Felix A. Conte Department of Pediatrics University of California San Francisco, CA 94141, USA
Oral Sexy Steroids Pharmacology of the Contraceptive Steroids Edited by Joseph W. Goldzieher and Kenneth Fotherby. New York, Raven, 1994, $99.00
(xv + 463 pages),
ISBN
U-7817-0097-3. This is a comprehensive review of the metabolism, pharmacokinetics, and effects of a number of steroid contraceptive agents. These include the ethynylated estrogens, the norethindrone and norgestrel groups of 19-norprogestins, the acetoxyprogestins, and their longacting derivatives. An introductory chapter is followed by 29 chapters contributed by many authors. The first chapter of 12 pages, by Nicola Perone, with the undramatic title “The Progestins,” is the melodramatic story of science, intrigue and crime accompanying the discovery of the first effective progestins that served as the beginning of the contraceptive steroid age. The chapter reads like an adventure novel and would serve as the script for an Indiana Jones film. In fact, the story has been made into a film in Germany. The rest of the book is a more prosaic but useful reference text for gynecologists, certain internists and epidemiologists, and pharmacologists with special interests in these agents. 01994, Elsevier Science
Inc., 1043-2760/94/$7.00
Parts of the book are not particularly easy to read. The reader may plow through sometimes confusing details in the longer chapters, only to learn that no conclusion can be reached about the topics therein. It is disappointing that several contributors have failed to add a summary or conclusion about the present state of the topic. The confusion surrounding contraceptive steroids and their actions occurs when different laboratories use different methodologies that cannot be compared directly. Attempts to compare steroid metabolic and pharmacokinetic data between species or races are frequently unsuccessful because of wide interindividual, intraindividual, and species differences. The reader is left with the impression that the study of oral contraceptives has been haphazard rather than systematic. This must have made it difficult for the editors to produce an entirely readable book. The first page of each chapter leads one to believe that Goldzieher was the sole editor. In addition to the first chapter on the history of progestins as contraceptive agents, there is a very good account, entitled “Issues in Animal Pharmacology,” of the strengths and weaknesses of various assays to determine useful clinical properties. Another fine chapter discusses TEM Vol. 5, No. 6, 1994
deleterious side-effects at this time, apart from a few individuals predisposed to
oid-induced teratogenesis sis describes possibilities,
variable decrease efficacy of both the drug and the contraceptive agent. Much remains to be learned about this important and clinically useful phenomenon.
certain clinical abnormalities.
the absence
A large section of the book, comprising 18 chapters, seeks to describe the possible
side-effects of contraceptive steroids on a large number of bodily systems and on biochemical and physiologic functions.
chapters
to be little
approach
evidence
for
steroids. A chapter on ster-
There
The pharmacokinetics and metabolism of the steroids are given in great detail, but it is disconcerting to read the details only to learn of the inadequacy of the methods used to generate much of the data. The large number of pharmacokinetic constants presented would appeal probably only to the most committed of pharmacologic researchers in the field. The variability of steroid metabolite patterns formed in different species of animals and different races of humans will interest some readers, although the clinical relevance of these differences is often obscure.
seems
contraceptive
the interactions between oral contraceptives and certain drugs, such as anticonvulsants and antibiotics, resulting in a
Two of the
the problem
from an
interesting perspective. In a chapter on the effect of oral contraceptive steroids on the blood coagulation system, steroid effects are noted on many coagulation factors; nevertheless, there is no clear indication of interference with blood coagulation as a whole. In another section, there are steroidal effects on individual steps in carbohydrate metabolism, as well as on its insulin relationships, but it is concluded that there is no strong clinical evidence for a generally disordered carbohydrate metabolism due to the contraceptive steroids. This leads to a strong statement to the effect that witholding contraceptive steroids from patients with diabetes is counterproductive and that use of contraceptives is less likely to cause problems than would an unwanted pregnancy in a diabetic patient. The obligatory chapter on steroid action adds little to our knowledge of the
of many
and mutagenepresumably in facts.
The
final
chapter discusses the evaluation of efficacy and safety and describes the need for improved case studies. The book is well printed.
In only one
chapter could I discern overcrowding of graphs resulting in print too small to be easily read. Each chapter is accompanied liberally by references; in one case there are as many as 200. The volume is a genuine “everything in the literature about contraceptive steroids.” It has obviously not been possible to present “everything you really wanted to know” about the topic. It may, however, act as a spur to draw attention to what needs to be done to provide more information. TEM Ronald Hobkirk Department of Biochemistry University of Western Ontario London, Ontario, Canada N6A 5Cl
Risky Genes The Calculation of Genetic Risks: Worked Examples in DNA Diagnostics
family?” or ‘Will the next child be afflicted?” Long-forgotten courses in genetics hardly equip one to provide answers, and the help of a specialist is usually sought. This little book, read with the care it deserves, provides insight into the techniques of calculating genetic risks.
By Peter J. Bridge. Baltimore, Johns Hopkins,
1994, $45.00
(ix + 195), ISBN
0-8018-4678-l. A perk of being Book Review Editor
of
TEM is to be able to browse through the books as they arrive. Most of the books are assigned to other reviewers; those that fall within my areas of interest I may review myself.
This little book
is well
outside my field, but leafing through recognized
it I
its unusual style and I took it
with me on a trip. The book provided me with many air travel hours of pleasure. Inherited endocrine diseases range from the very rare to commonplace. In a busy medical center there are many occurrences of even rare diseases, with repeated occasions “Who carries
to ask questions such as
the defective
TEM Vol. 5, No. 6, 1994
gene in the
At first glance, an algebraic relationship looks formidable because of unfamiliarity with the factors in the equation. The author of this book, Peter Bridge, carefully avoids equation shock by explaining relationships in plain English first and then introducing the mathematics. The hitherto befuddling calculations become clear and even selfevident. However, the author assumes
through the calculation of genetic risk, first using only the information available from a pedigree. Who in the family tree was afflicted? Which members are likely carriers? What is the significance of multiple unafflicted offspring in the calculation of risk? Then the author introduces information obtained from DNA analysis of marker genes-those genes that accompany the gene carrying the disease, but do not cause the disease. The DNA information increases the accuracy of estimating genetic risk by orders of magnitude! The power of the new technology is demonstrated beautifully by comparing the information obtained with and without the DNA analysis. As more
that the reader is aware of the basic concepts of heredity, such as the simple facts of Mendelian inheritance, what recessive and dominant mean, and the difference between autosomal and sexlinked inheritance. With these basics as a springboard, the book leads the reader
and more gene markers become available, the accuracy will increase correspondingly. Even with current knowlof chromosomal edge, the origin fragments after complex rearrangements can be traced to ancestors several generations before the patient’s.
01994. Elsevier Science Inc., 1043-2760/94/$7.00
263
(xiii + 808 pages),
ISBN-O-8246-8651-3. contains 14 multi-authored chapters covering the effects of hormones, growth factors, and proto-oncogenes on fetal development. The chapters are comprehensive, well written, and authored by acknowledged experts. The editors intended the book to be useful to obstetrician-gynecologists, neonatologists, pediatric endocrinologists, physiologists, and others interested in fetal growth and development. The book begins with two chapters on the fetal adrenal. However, it might have been more logical to begin with chapter 2, “Physiopathology of the Fetal Adrenal,” rather than with chapter 1, “Inborn Errors of Steroidogenesis.” Both chapters, however, are excellent in their coverage of these subjects. Chapters 4, 5, and 6 deal with sex differentiation. Dr. Josso’s chapter on anti-Mullerian hormone and Dr. Simpson’s review of disorders of sex differentiation are well worth reading. However, three chapters on sex differentiation may be more than are needed, and I found some information to be repetitive. Following these are three chapters on the physiopathology of the placenta. Chapter 8 by Drs. Casey and MacDonald on steroid production in the placenta is absolutely clear, concise, and comprehensive. Chapter 12 by Dr. Ojasoo et al. addresses the effects of prenatally administered sex steroids on the fetus. This chapter tends to be encyclopedic in its approach and is disappointing in that it does not include the issues of the effects of prenatal sex steroids on behavior and gender identity in humans. The real highlight of this book is chapter 13,“Proto-Oncogenes in Fetal Life.” This chapter deals with the molecular biology of proto-oncogenes in the fetus. The author, Dr. Swaneck, assumes correctly that some readers might not be familiar with the techniques and terminology of molecuHormones and Fetal Pathophysiology
262
lar biology. Therefore the first third of the chapter is a very well written, comprehensive, and informative primer on molecular biology, which makes the rest of the chapter clear even to the nonmolecular biologist. Probably because it is multi-authored and rather long, this is a difficult book to read in its entirety. Chapters of particular interest should be selected by the reader. The absence of a chapter on thyroid hormone synthesis and fetalmaternal thyroid relationships is a serious omission in this book. Also, I am disappointed by the scarcity of information on gonadotrophins, human chorionic sommatomammotrophin, and
growth hormone in relationship to fetal growth and development. After reading this book, I had learned a lot; however, I did not feel that I had a complete understanding of the effect of hormones on the fetus and its development in utero. This is a valuable text for its intended readership, and I recommend that it be available for reference purposes in hospital and medical school libraries. TEM Felix A. Conte Department of Pediatrics University of California San Francisco, CA 94141, USA
Oral Sexy Steroids Pharmacology of the Contraceptive Steroids Edited by Joseph W. Goldzieher and Kenneth Fotherby. New York, Raven, 1994, $99.00
(xv + 463 pages),
ISBN
U-7817-0097-3. This is a comprehensive review of the metabolism, pharmacokinetics, and effects of a number of steroid contraceptive agents. These include the ethynylated estrogens, the norethindrone and norgestrel groups of 19-norprogestins, the acetoxyprogestins, and their longacting derivatives. An introductory chapter is followed by 29 chapters contributed by many authors. The first chapter of 12 pages, by Nicola Perone, with the undramatic title “The Progestins,” is the melodramatic story of science, intrigue and crime accompanying the discovery of the first effective progestins that served as the beginning of the contraceptive steroid age. The chapter reads like an adventure novel and would serve as the script for an Indiana Jones film. In fact, the story has been made into a film in Germany. The rest of the book is a more prosaic but useful reference text for gynecologists, certain internists and epidemiologists, and pharmacologists with special interests in these agents. 01994, Elsevier Science
Inc., 1043-2760/94/$7.00
Parts of the book are not particularly easy to read. The reader may plow through sometimes confusing details in the longer chapters, only to learn that no conclusion can be reached about the topics therein. It is disappointing that several contributors have failed to add a summary or conclusion about the present state of the topic. The confusion surrounding contraceptive steroids and their actions occurs when different laboratories use different methodologies that cannot be compared directly. Attempts to compare steroid metabolic and pharmacokinetic data between species or races are frequently unsuccessful because of wide interindividual, intraindividual, and species differences. The reader is left with the impression that the study of oral contraceptives has been haphazard rather than systematic. This must have made it difficult for the editors to produce an entirely readable book. The first page of each chapter leads one to believe that Goldzieher was the sole editor. In addition to the first chapter on the history of progestins as contraceptive agents, there is a very good account, entitled “Issues in Animal Pharmacology,” of the strengths and weaknesses of various assays to determine useful clinical properties. Another fine chapter discusses TEM Vol. 5, No. 6, 1994
deleterious side-effects at this time, apart from a few individuals predisposed to
oid-induced teratogenesis sis describes possibilities,
variable decrease efficacy of both the drug and the contraceptive agent. Much remains to be learned about this important and clinically useful phenomenon.
certain clinical abnormalities.
the absence
A large section of the book, comprising 18 chapters, seeks to describe the possible
side-effects of contraceptive steroids on a large number of bodily systems and on biochemical and physiologic functions.
chapters
to be little
approach
evidence
for
steroids. A chapter on ster-
There
The pharmacokinetics and metabolism of the steroids are given in great detail, but it is disconcerting to read the details only to learn of the inadequacy of the methods used to generate much of the data. The large number of pharmacokinetic constants presented would appeal probably only to the most committed of pharmacologic researchers in the field. The variability of steroid metabolite patterns formed in different species of animals and different races of humans will interest some readers, although the clinical relevance of these differences is often obscure.
seems
contraceptive
the interactions between oral contraceptives and certain drugs, such as anticonvulsants and antibiotics, resulting in a
Two of the
the problem
from an
interesting perspective. In a chapter on the effect of oral contraceptive steroids on the blood coagulation system, steroid effects are noted on many coagulation factors; nevertheless, there is no clear indication of interference with blood coagulation as a whole. In another section, there are steroidal effects on individual steps in carbohydrate metabolism, as well as on its insulin relationships, but it is concluded that there is no strong clinical evidence for a generally disordered carbohydrate metabolism due to the contraceptive steroids. This leads to a strong statement to the effect that witholding contraceptive steroids from patients with diabetes is counterproductive and that use of contraceptives is less likely to cause problems than would an unwanted pregnancy in a diabetic patient. The obligatory chapter on steroid action adds little to our knowledge of the
of many
and mutagenepresumably in facts.
The
final
chapter discusses the evaluation of efficacy and safety and describes the need for improved case studies. The book is well printed.
In only one
chapter could I discern overcrowding of graphs resulting in print too small to be easily read. Each chapter is accompanied liberally by references; in one case there are as many as 200. The volume is a genuine “everything in the literature about contraceptive steroids.” It has obviously not been possible to present “everything you really wanted to know” about the topic. It may, however, act as a spur to draw attention to what needs to be done to provide more information. TEM Ronald Hobkirk Department of Biochemistry University of Western Ontario London, Ontario, Canada N6A 5Cl
Risky Genes The Calculation of Genetic Risks: Worked Examples in DNA Diagnostics
family?” or ‘Will the next child be afflicted?” Long-forgotten courses in genetics hardly equip one to provide answers, and the help of a specialist is usually sought. This little book, read with the care it deserves, provides insight into the techniques of calculating genetic risks.
By Peter J. Bridge. Baltimore, Johns Hopkins,
1994, $45.00
(ix + 195), ISBN
0-8018-4678-l. A perk of being Book Review Editor
of
TEM is to be able to browse through the books as they arrive. Most of the books are assigned to other reviewers; those that fall within my areas of interest I may review myself.
This little book
is well
outside my field, but leafing through recognized
it I
its unusual style and I took it
with me on a trip. The book provided me with many air travel hours of pleasure. Inherited endocrine diseases range from the very rare to commonplace. In a busy medical center there are many occurrences of even rare diseases, with repeated occasions “Who carries
to ask questions such as
the defective
TEM Vol. 5, No. 6, 1994
gene in the
At first glance, an algebraic relationship looks formidable because of unfamiliarity with the factors in the equation. The author of this book, Peter Bridge, carefully avoids equation shock by explaining relationships in plain English first and then introducing the mathematics. The hitherto befuddling calculations become clear and even selfevident. However, the author assumes
through the calculation of genetic risk, first using only the information available from a pedigree. Who in the family tree was afflicted? Which members are likely carriers? What is the significance of multiple unafflicted offspring in the calculation of risk? Then the author introduces information obtained from DNA analysis of marker genes-those genes that accompany the gene carrying the disease, but do not cause the disease. The DNA information increases the accuracy of estimating genetic risk by orders of magnitude! The power of the new technology is demonstrated beautifully by comparing the information obtained with and without the DNA analysis. As more
that the reader is aware of the basic concepts of heredity, such as the simple facts of Mendelian inheritance, what recessive and dominant mean, and the difference between autosomal and sexlinked inheritance. With these basics as a springboard, the book leads the reader
and more gene markers become available, the accuracy will increase correspondingly. Even with current knowlof chromosomal edge, the origin fragments after complex rearrangements can be traced to ancestors several generations before the patient’s.
01994. Elsevier Science Inc., 1043-2760/94/$7.00
263