Hydroxyprogesterone in Pregnancy and Breastfeeding
Fetal Risk Summary
The FDA mandated deletion of pregnancy-related indications from all progestins because of a possible association with congenital anomalies. Ambiguous genitalia of both male and female fetuses have been reported with hydroxyprogesterone (see also Norethindrone, Norethynodrel) (1,2 and 3).
The Collaborative Perinatal Project monitored 866 mother-child pairs with 1st trimester exposure to progestational agents (including 162 with exposure to hydroxyprogesterone) (4, pp. 389, 391). An increase in the expected frequency of cardiovascular defects and hypospadias was observed for both estrogens and progestogens (4, p. 394; 5). Reevaluation of these data in terms of timing of exposure, vaginal bleeding in early pregnancy, and previous maternal obstetric history, however, failed to support an association between female sex hormones and cardiac malformations (6).
Dillon (7,8) reported six infants with malformations exposed to hydroxyprogesterone during various stages of gestation. The congenital defects included spina bifida, anencephalus, hydrocephalus, tetralogy of Fallot, common truncus arteriosus, cataract, and ventricular septal defect. Complete absence of both thumbs and dislocated head of the right radius in a child have been associated with hydroxyprogesterone (8). Use of diazepam in early pregnancy and the lack of similar reports make an association doubtful.
A 1985 study described 2,754 offspring born to mothers who had vaginal bleeding during the 1st trimester (9). Of the total group, 1,608 of the newborns were delivered from mothers treated during the 1st trimester with either oral medroxyprogesterone (2030 mg/day), 17-hydroxyprogesterone (500 mg/week by injection), or a combination of the two. Medroxyprogesterone was used exclusively in 1,274 (79.2%) of the study group. The control group consisted of 1,146 infants delivered from mothers who bled during the 1st trimester but who were not treated. There were no differences between the study and control groups in the overall rate of malformations (120 vs. 123.9/1000, respectively) or in the rate of major malformations (63.4 vs. 71.5/1000, respectively). Another 1985 study compared 988 infants, exposed in utero to various progesterones, to a matched cohort of 1,976 unexposed controls (10). No association between the use of progestins, primarily progesterone and 17-hydroxyprogesterone, and fetal malformations was discovered.
Developmental changes in the psychosexual performance of boys has been attributed to in utero exposure to hydroxyprogesterone (11). The mothers received an estrogen-progestogen regimen for their diabetes. Hormone-exposed males demonstrated a trend to have less heterosexual experience and fewer masculine interests than controls.
The use of high-dose hydroxyprogesterone during the 2nd and 3rd trimesters has been advocated for the prevention of premature labor (12,13). However, the use of the steroid was not effective in twin pregnancies (14). Fetal adverse effects were not observed.
Breast Feeding Summary
No data are available.
- Dayan E, Rosa FW. Fetal ambiguous genitalia associated with sex hormone use early in pregnancy. ADR Highlights 1981:114. Food and Drug Administration, Division of Drug Experience.
- Wilkins L. Masculinization of female fetus due to use of orally given progestins. JAMA 1960;172;102832.
- Wilkins L, Jones HW, Holman GH, Stempfel RS Jr. Masculinization of the female fetus associated with administration of oral and intramuscular progestins during gestation: non-adrenal female pseudohermaphrodism. J Clin Endocrinol Metab 1958;68:55985
- Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA:Publishing Sciences Group, 1977.
- Heinonen OP, Slone D, Monson RR, Hook EB, Shapiro S. Cardiovascular birth defects and antenatal exposure to female sex hormones. N Engl J Med 1977;296:6770.
- Wiseman RA, Dodds-Smith IC. Cardiovascular birth defects and antenatal exposure to female sex hormones: a reevaluation of some base data. Teratology 1984;30:35970.
- Dillon S. Congenital malformations and hormones in pregnancy. Br Med J 1976;2:1446.
- Dillon S. Progestogen therapy in early pregnancy and associated congenital defects. Practitioner 1970;205:804.
- Katz Z, Lancet M, Skornik J, Chemke J, Mogilner BM, Klinberg M. Teratogenicity of progestogens given during the first trimester of pregnancy. Obstet Gynecol 1985;65:77580.
- Resseguie LJ, Hick JF, Bruen JA, Noller KL, O'Fallon WM, Kurland LT. Congenital malformations among offspring exposed in utero to progestins, Olmsted County, Minnesota, 19361974. Fertil Steril 1985;43:5149.
- Yalom ID, Green R, Fisk N. Prenatal exposure to female hormones. Effect on psychosexual development in boys. Arch Gen Psychiatry 1973;28:55461.
- Johnson JWC, Austin KL, Jones GS, Davis GH, King TM. Efficacy of 17-hydroxyprogesterone caproate in the prevention of premature labor. N Engl J Med 1975;293:67580.
- Johnson JWC, Lee PA, Zachary AS, Calhoun S, Migeon CJ. High-risk prematurity-progestin treatment and steroid studies. Obstet Gynecol 1979;54:4128.
Hartikainen-Sorri AL, Kauppila A, Tuimala R. Inefficacy of 17-hydroxyprogesterone caproate in the prevention of prematurity in twin pregnancy. Obstet Gynecol 1980;56:6925.
Questions and Answers
What's Wrong With My 17-Hydroxyprogesterone?, I just got my blood test back...and it saysthat my 17-Hydroxyprogesterone level is 4.98 NG/ML...does this mean it's high? or low? What would be the cause of this? How do I get it back to normal?
btw...if this helps...I believe I has in the luteal phase (of my menstrual cycle)..whatever that means :)...and there's no pregnancy.
Luteal Phase Defect
Randine Lewis, Ph.D., Lic.Ac.
The luteal phase of the menstrual cycle spans from ovulation at midcycle
until menstruation. The luteal phase should last for at least 12
to 14 days. A luteal phase which is less than 10 days will have
difficulty producing an environment favorable for implantation.
The luteal phase derives its name from the fact that the luteinized
cells from the collapsed follicle undergo a structural transformation in
response to increased vascularization, a process known as
luteinization. Thereafter these two cell types produce progesterone;
one of which is dependent on the secretion of luteinizing hormone.
Progesterone is secreted to prepare the uterine lining for
implantation. The ovary also secretes other hormones as well -
inhibin, relaxin, and 17-hydroxyprogesterone.
The endometrium, meanwhile, under the influence of estrogen during
the proliferative phase, develops progesterone receptors.
Progesterone then causes the uterine lining to become secretory in
nature. The most important aspect here is that there is a window of
implantation, where certain proteins appear on the epithelial cells of
the endometrial lining and then disappear. When they are gone, the
period of endometrial receptivity has passed. If these factors are not
present, implantation will not occur. Many factors affect this window
of implantation. Mucinous substances are secreted by glands within
the endometrium during this same time period in women without
implantation problems. These factors cannot be effectively treated
with just a pill or hormonal supplementation. A biopsy may reveal the
presence of these defects, but doesn't tell us how it occurred, why it
happened, or what do do about it.
When a pregnancy occurs, and the developing blastocyst burrows
into the uterine lining, the embryo will secrete hCG, which stimulates
the ovary to produce more progesterone. This process is called luteal
rescue. If this process happens too late or if pregnancy does not
occur, LH stimulation decreases, progesterone levels decrease and
uterine prostaglandins are released. This causes the corpus luteum
to shrivel. The uterine lining, because of lack of progesterone
stimulation, is shed.
This series of events begins not in the luteal or secretory phase but in
the follicular or proliferative phase, early in the cycle. This
synchronized process is orchestrated by all of the reproductive
hormones, and each of the factors necessary for implantation, known
and unknown, are initiated by another process. No event in
reproductive medicine is an isolated occurrence, but as with all other
reproductive medicine is an isolated occurrence, but as with all other
physiologic processes, each event is interdependent on the proper
workings of the entire reproductive system. This much we know
about the immediate state of the endometrium. There is much more
which we don't know, which includes the hormonal relationships,
stress effects, and underlying pathological imbalances. This is where
other modalities of healing can reveal their striking impact.
Most infertility specialists consider a luteal phase defect to be an
insufficiency of progesterone production. This is certainly a major
aspect of this dysfunction; however, if this were the only element to
consider, the administration of exogenous progesterone would cure
the defect. Anyone who has been diagnosed with this defect and
treated with progesterone realizes the immense frustration in trying to
treat this deficiency. Some studies have also demonstrated impaired
folliculogenesis in women with luteal phase defects, and surely luteal
phase defects indicate defective follicular development; other studies
have implicated impairment in the levels of FSH or LH to be
causative. They probably all play a role in different degrees in each
individual woman with this presentation.
Luteal phase defect also includes a definition that the events
signaling endometrial development are out of sync with the rest of the
hormonal cycle, and the uterine lining actually lags behind the
hormonal queues. Therefore if an egg was released and fertilized,
the blastocyst would find the endometrium unreceptive for
implantation, and it would pass on through undetected.
It is generally agreed upon that progesterone has a hyperthermal
effect, which raises the basal body temperature at least four-tenths of
one degree to one full degree Fahrenheit after ovulation. The
temperatures and thus the progesterone levels should remain
elevated for fourteen days after ovulation. Progesterone levels peak
during the middle of the luteal phase, about one week after ovulation.
If the corpus luteum is not producing adequate quantities of
progesterone, or if the uterine lining is not properly prepared for the
role of progesterone, spotting may occur, the basal body temperature
may drop, or the period may come early.
The Eastern View
Shifting to an Eastern paradigm and using the basal body
temperature chart as a prototype of the hormonal system, Phase I is
the menstrual, blood, or zero (hormonal resting) stage. Phase II is the
follicular, estrogen dominated yin stage. During the ovulatory stage,
yin reaches its apogee and transforms into yang, only if qi, blood, yin
and yang are optimally functioning. Phase III is the luteal phase,
governed by the yang hormone progesterone. This phase can thrive
only if the previous phases have fulfilled their particular roles.
Most luteal phase defects include a diagnosis of low progesterone.
Since this hormone is governed by the kidney yang and the spleen
qi, these two elements almost always need supplementation.
qi, these two elements almost always need supplementation.
However, Chinese medicine views this process beyond what is
happening in the immediate luteal phase. The other phases need to
be in harmony; adequate substrate needs to be present; and no
obstruction - mechanical, anatomical or energetic, may be present if
the luteal phase is to be in sync. Hence, there can be many reasons
for luteal phase insufficiency: not enough yin to transform into yang,
obstructed blood, liver qi stagnation, or not enough kidney yang or
spleen qi the hold the luteal phase. This is where the correct pattern
discrimination makes the difference in treatment outcome.
Most often the basal body temperature chart will reveal the
manifestation of the disharmony during the luteal phase temperature.
For instance, in one form of luteal phase insufficiency, the
temperatures may go along during the follicular phase as normal, the
fertile cervical fluid appears, and in all appearance ovulation has
occurred. The fertility monitor says ovulation has occurred. However,
the temperatures do not rise dramatically. The woman might be
particularly fatigued around ovulation. She may sweat spontaneously
during the luteal phase. She may be prone to abdominal cramping
and loose stools. She has a history of low blood pressure, and she
can always tell she is going to get her period because her stools
become looser and more profuse. She bleeds heavily, but the blood
is somewhat thin and watery and appears almost pink in color. Her
energy is especially low during her period. According to the
diagnostics of Traditional Chinese Medicine, this woman fits the
category of "Spleen Qi Vacuity". Therefore, the only way to correct
this defect is to supplement her spleen qi. We could give her
progesterone supplements or Angelica (a.k.a. Tang Kuei or Dang
Gui, an herb which supplements and invigorates the blood and
regulates menstruation) all day long, and she would likely get no
response. However, if she made some minor dietary modifications
and supplemented her diet with herbs such as Ginseng, Atractylodes,
Dioscoreae, and Astragalus; her luteal phase defect should correct
itself and she will be able to conceive. She should avoid too many
raw foods like cold salads. She should not eat too many sweets or
refined carbohydrates. This includes white bread and rice cakes, or
any boxed or packaged noodles. Anything that is converted to
glucose too quickly after ingestion becomes sugar as far as the body
is concerned, and damages the spleen. This diet regulates blood
sugar levels, as well. The best diet would be organic vegetables, light
amounts of protein, but not those that have been hormonally treated,
and some fruits, but not fruit juices. Complex carbohydrates and
whole grain breads are fine.
If the basal body temperature chart raises, lowers, and raises again,
it indicates dysfunction of the corpus luteum functioning. The
Traditional Chinese Medical diagnosis might support that there is an
insufficiency of the spleen qi to support the yang of the kidney.
Kidney Yang Vacuity
Kidney yang vacuity is another commonly seen luteal phase defect.
In this case the temperatures stay low during the follicular phase as
they should. The woman in fact always feels cold. Her feet are
especially cold at night. Mid-cycle vaginal discharge appears on
schedule, and is even profuse in amount. Ovulation occurs, but she
has almost no sexual desire, so intercourse feels like a chore. Her
basal body temperatures never rise very much. The pre-ovulatory
and post-ovulatory baselines differ only by about two-tenths of a
degree. Her back is almost always weak and sometimes feels sore.
She sleeps well, but has to wake up to urinate at least one or two
times per night. Sometimes she spots about a week before her
period is due. She can usually tell that she is not pregnant, and that
her period is coming because her back aches more than usual. Her
bowel movements become somewhat loose the day she starts
Diagnostically, this woman most closely resembles the kidney yang
vacuity scenario in Chinese gynecological diagnosis. She also has
some symptoms of spleen qi vacuity, but since the kidney yang is
high 17 hydroxyprogesterone levels?, so i went to my new gyno on jan 15th she gave me 10 mg provera for 10 days i got y blood work dont on the 21st
and now i got my results back and the only thing that was wrong was my high 17 hydroxyprogesterone levels..
the level is 380
what can cause high 17 hydroxyprogesterone levels??
is it normal to be high??
can anyone give me any advise about high 17 hydroxyprogesterone levels...
sorry, i have no idea maybe your pregnant????
How do I work out the orignial concentration?, I pipetted 5ml of sample and added 2mls of 0.1M phosphate buffer (pH6.0). I then eluted 3mls of the sample into a prepared SPE cartridge.
From my chromatographic results obtained from the acid/neutral fraction analyzed I need to calculate the original concentration of Hydrocortison, Corticoserone and 1-hydroxyprogesterone in the sample.
To do this, you need to calculate the aliquoting factor or the dilution factor. Then apply this to the value you obtained for each analyte. So, 5 ml of original sample diluted to 7 mls represents a 1.4 fold dilution or a 40% dilution. At this point, I'm not sure what you then did. You state that you eluted 3 mls into a cartridge, but eluted from what, a column? If so, how much was applied to the column? Whatever you did, just work backwards and keep track of the dilutions, etc.
How effective is an injection that is given in the wrong location and not deep enough?, My doctor has ordered alpha-hydroxyprogesterone caproate injections to be given IM. Every time I get my injections the medical assistant is giving them waist high and they are not deep. Could this compromise the effectiveness of my injection? Should I express my concern to my doctor?
You need to tell the doc if only so that the MA gets proper training in giving injections--I suspect you are not the only one getting injections in the wrong place.
Medications that need to be IM need the blood supply of the muscle to get fully absorbed, which fat does not have (sounds like you are getting them sub cutaneously), so yes, it is possible to get less effective release & absorbtion of medication. Certain meds need to be placed in other areas of the body to not result in damage to the wrong type of tissue as well, due to their pH, quantity etc. Others need to be in certain areas (ie TB) to stimulate the correct response to be considered accurate.
So yes, please discuss with the MD--to sort yourself out and to benefit others getting injections.